NBIC research news

Different backgrounds, common benefits

Fri, 24 May 2013 13:18:00 +0200

Interdisciplinary research fields like bioinformatics and systems biology require a broad range of skills and a thorough understanding of diverse scientific disciplines like biology, mathematics and informatics. In the Netherlands, university programmes in bioinformatics and/or systems biology are only taught at the MSc level. As a result, students enrolling in such a programme have very mixed backgrounds, including biology, mathematics, computer science, artificial intelligence, biomedical science and software engineering. Designing a curriculum that is equally challenging and attractive for such a diverse population is a real challenge in itself.

In a paper in Briefings in Bioinformatics, Sanne Abeln (VU University Amsterdam) and colleagues describe their experiences and learning points from the Bioinformatics and Systems Biology MSc programme, a joint effort between the two Amsterdam-based universities. Instead of tailoring the curriculum to the specific needs of the various subgroups in the student population (e.g. offering more programming courses to biology BSc's and vice versa), they have opted for early mixing of students with different backgrounds in intensive group projects, with specialized conversion classes to bridge gaps in knowledge and skills. To the students, this mixed environment is very stimulating, offers them insight in their own gaps in knowledge and is a good preparation for their future fields of employment.

Abeln S, Molenaar D, Feenstra KA, Hoefsloot HC, Teusink B, Heringa J
Bioinformatics and Systems Biology: bridging the gap between heterogeneous student backgrounds
Brief Bioinform. 2013 Apr 19 Text by Esther Thole.

The Power of RNA seq

Thu, 23 May 2013 14:19:00 +0200

The NBIC Research PhD School for Bioinformatics and Computational Biology was announced to the NBIC Faculty during the Netherlands Bioinformatics Conference (NBIC2013) in April this year. The NBIC research school will thrive on the cooperation with related universities and research groups, and local graduate schools. ‘The power of RNA-seq’ course will be one of the first activities ‘avant la lettre’. This introductory course is organised by the Wageningen University graduate school Experimental Plant Sciences (EPS) and NBIC for both PhD students of EPS & WUR staff and national NBIC participants.

Date: June 5-7th, 2013
Venue: Wageningen University, the Netherlands
Organised by: Graduate School Experimental Plant Sciences (EPS) & NBIC
Keywords: designing your RNA-seq experiment, sequencing, mapping, quality control & statistics, RNA-seq data analysis pipeline, transcript identification, differential expression, special applications of RNA-seq, extracting biology.

This 3-day course consists of lectures in the morning and extensive hands-on computer practicals in the afternoon using Galaxy, R and webtools. You'll learn about all aspects of RNA-seq during the morning lectures, but also the context, applicability, power and expected results of RNA-seq experiments are covered. During the practicals you'll learn the basic steps an RNA-seq pipeline consist of, how to interpret your data and to put the results to use in your research project.

There are still seats available and you can register via the application form.

Contact: Patrick Koks (education@nbic.nl)

Still some seats left for Variant Detection and Interpretation

Thu, 23 May 2013 14:12:00 +0200

Thera are still a few seats left for next week's course "Variant Detection and Interpretation in a Diagnostic Context”. This advanced NGS course will be held for the second time and is this year organised in Rotterdam. The course is accredited by VKGL for the Laboratory Specialist Clinical Genetics track for 6 credit point per day.

Date: May 27-29th, 2013
Venue: Erasmus MC, Rotterdam, the Netherlands
Organised by: NBIC, EMC, LUMC, UMC St. Radboud, CGD
Keywords: Lab methods, Read Mapping, Variant Calling, Quality Control, Annotation of Variants, Computational Predictions, Evaluation and Reporting of results, Validation, Clinical Interpretation & Relevance, Legal & Ethical issues.

The mixed programme aims at implementing and applying NGS techniques as a diagnostic tool in the clinic and targets all aspects involved. The course is intended for bioinformaticians, researchers and molecular & clinical geneticists. The varied programme consists of lectures and hands-on workshops and will appeal to those analysing, using or applying NGS techniques and results thereof for the genetic diagnosis of patients. The course is intended for people with experience in (NGS) data analysis or the application of NGS-based diagnostic tools.

Registration: http://www.nbic.nl/education/nbic-phd-school/enrolment/genomreseqappform2013/

Contact: Patrick Koks (education@nbic.nl)

Enlighten Your Research Global competition - Call for Proposals

Thu, 23 May 2013 10:50:00 +0200

The competition for researchers “Enlighten Your Research” - successful in the Netherlands - now becomes International! The Enlighten Your Research Global (EYR-Global) program is an international competition that invites researchers and their collaborators to submit proposals that highlight how access to world-class research networks would significantly improve their research and discovery process.

Modern science is generating large amounts of data and timely data transfers are a crucial aspect for the emerging international scientific collaborations. High-speed networks are an important enabler for the sharing of these large amounts of data. In many cases, researchers are unaware of the possibilities of such high-speed networks, offered by their National Research and Education Networks (NREN’s). In order to help researchers with their international collaborations and to further promote the benefits of international-scale networking to researchers, five leading NRENs are working together to create an exciting opportunity for the research communities.

Researchers from any discipline are invited to submit a proposal with challenging research questions. The program is open to a wide range of research teams - ranging from novice to expert in the use of information technology - to support their research projects to participate in the competition.

The competition winners will have access to:

World-class network infrastructure operated by the NRENs and their partners.
Support and advice on end-to-end network connectivity.
NREN commitment to an agreed level of network resource provisioning and support during the competition period.

Visit http://www.enlightenyourresearch.net to find details of the competition, its timeline and the procedure for submitting a draft proposal.

Important dates

Monday June 24, 2013: Submission deadline draft proposal
Friday August 2, 2013: Notification 1st round winners:
July 30 - September 30, 2013 Consultation round for fine-tuning proposal and technical feasibility
Monday October 14, 2013: Submission deadline final proposal
December 2013: Announcement of the winners
Early 2014: Award ceremony and Implementation of services awarded

Global Partners

ESnet (USA): http://www.es.net
Funet (Finland): http://www.csc.fi/english/institutions/funet/index_html
Internet2 (USA): http://www.internet2.edu
Janet (UK): https://www.ja.net/products-services/janet-research
SURFnet (NL): http://www.surfnet.nl/en/Pages/default.aspx

Please email info@enlightenyourresearch.net if you have any questions.

NBIC Research School for Bioinformatics & Computational Biology

Thu, 16 May 2013 13:51:00 +0200

Activities to set up the NBIC Research PhD School for Bioinformatics and Computational Biology are gaining momentum. The NBIC Research School aims to offer a vibrant national environment for the scientific development and education of integrative bioinformatics and computational (systems) biology. The research school should sustain and foster the close research community that NBIC has built over the years. ‘The power of RNA-seq’ course will be one of the first activities ‘avant la lettre’. This introductory course is organised by the Wageningen University graduate school Experimental Plant Sciences (EPS) in close collaboration with NBIC. for both PhD students of EPS & WUR staff and national NBIC participants. The research school should underpin the integrative and cross-disciplinary activities within the Dutch Techcenter for the Life Sciences (DTL) and closely liaise with DTL’s Data Integration and Stewardship Centre (DISC). During the NBIC faculty meeting preceding NBIC2013, it was decided to include the computational aspects of systems biology in the main focus of the research school, which will yield a tight-knit, homogeneous community in bioinformatics and computational biology. One of the main missions of the research school will be organising NBIC2014 and beyond. It is currently looked into what sustainable format the workshop may be organised in the years to come.

EBI Roadshow on its way from Amsterdam to Maastricht

Thu, 16 May 2013 13:41:00 +0200

In April the first two days the EBI Roadshow were hosted by the group of Antoine van Kampen at the AMC. Aldo Jongejan coordinated the local organisation of the training modules which covered the topics Introduction to databases, Sequence Alignment, Ensembl and ArrayExpress. The AMC Research Council sponsored 12 seats for AMC researchers.

In total 26 participants joined the lectures of the EBI delegates Andrew Cowley, Amy Tang and Denise Carvalho-Silva. The roadshow evaluation gave positive feedback like “Good overview of all possible options there are, now I have more insights in all the EBI stuff. Now I understand all the basics about Ensembl it is very easy to go into more details after this course and to explain the database(s) to other people now.”

The second part of the EBI Roadshow will be organized 1-3 July in Maastricht by the group of Chris Evelo with local organizer Egon Willighagen, and it will introduce the advanced uses of the gene and genomes databases, small molecule resources, the protein sequence databases, and interaction and pathway databases at EBI (a.o. UniPROT, ENSEMBL, CHEMBL, IntAct and Reactome). The roadshow in Maastricht will be extended with two course days (July 4-5 ) provided by the department of Bioinformatics-BiGCaT at Maastricht University in collaboration with the DiXa FP7 project on systems biology approaches in toxicogenomics. The second part (DiXa) of the course focuses on real data analysis using pathway and network approaches with links to the databases covered in first part (EBI Roadshow). Tools that will be used include WikiPathways, PathVisio and Cytoscape. Take a look at the course webpage for full details!

Journal of Web Semantics on Life Science and e-Science

Thu, 16 May 2013 11:55:00 +0200

The Journal of Web Semantics, well known particularly in the computer science field, is putting out a special issue on life science and e-science.This special issue is of interest to the bioinformatics community. Marco Roos (LUMC, NBIC) and Tim Clark (Harvard Medical School, Massachusetss General Hospital) are guest editors. Because the Netherlands is an important country in the fields of the Semantic Web, life science, and e-Science, they expect noteworthy submissions from the Netherlands. Marco Roos: "This is an opportunity for life scientists and computer scientists who work on the interface between the disciplines." Important dates
Paper submission deadline: July 31, 2013
Initial notification of acceptance (approximate): November 2013
Publication in early 2014

Full details http://www.journals.elsevier.com/journal-of-web-semantics/call-for-papers/web-semantics-on-life-science-and-e-science/

Bioinformatics in Berlin

Mon, 29 Apr 2013 13:20:00 +0200

July 19-23 the international conference ISMB/ECCB 2013 is organised in Berlin. Two workshops at this conference are co-organized by people from the NBIC network. Driven by the impact of technology in diverse areas, bioinformatics is becoming increasingly interdisciplinary, and in parallel so too are the audiences seeking bioinformatics training. That’s why Celia van Gelder (CMBI Nijmegen, NBIC) and her international colleagues in bioinformatics education are organising a workshop to bring awareness to the bioinformatics training needs of these new audiences. The workshop will consist of presentations on the topics of 1) how a medically trained audience thinks and learns about bioinformatics and the opportunities for new tools for the clinical setting; and 2) opportunities and strategies for providing bioinformatics training to an engaged, savvy public. Hienke Sminia (NBIC) will share her experiences with activities and exhibits for the general public (from ages 5 to 99). Marco Roos (LUMC) is co-organizing another workshop which explains what bioinformaticians need to know about digital publishing beyond the PDF. The aim of this workshop is to inform participants of ISMB/ECCB 2013 of changes and new opportunities in scientific communication. It addresses guidelines and tools that enable contributions to be exposed in machine-readable formats, ready for evaluation, interoperation, reuse, and attribution. In addition two Technology Track sessions will highlight aspects of digital publishing, one focussing on the ‘Open Pharmacological Space’, and one on Research Objects and Nanopublications as means to organising and exposing your methods and results in a digital form. NBIC partners associated with the Interoperability Task Force play a prominent role in organising these events and developing these standards More information about the workshops can be found on the conference website of ISMB/ECCB2013.

An inspiring place

Mon, 29 Apr 2013 12:01:00 +0200

Performing part of your PhD research in another lab is a good way to broaden your experience and enlarge your network. And to spend some time in another country. But it may lead to tangible results as well. Take the case of David van Dijk who visited the Weizmann Institute in Israel in 2010 using a NBIC Travel Grant. The result: a wet lab debut, two publications and a postdoc position.

David van Dijk performed his PhD research in the group of Peter Sloot at the University of Amsterdam. Although he already pondered the idea of visiting a lab abroad, things started moving when two PhD students from the group of Eran Segal (Weizmann Institute) came to Amsterdam. Van Dijk: "I was so impressed by their work that I decided to visit the Segal group. My supervisor Peter Sloot supported the idea and together we approached Eran Segal and got a positive response. Being a PhD student in bioinformatics, applying for a NBIC Travel Grant seemed the most logical thing to do."

Machine learning
He already knew Segal's work from the literature. "In my view, this group is one of the leading groups in computational biology. Segal's background is in artificial intelligence, just like mine, and he specializes in applying machine learning to biological problems. In addition, his lab is special because he runs both a dry and a wet lab and that was very appealing to me." With a background in informatics, the wet lab was unchartered territory to van Dijk, but this offered him the chance to explore that type of research as well. "I was lucky to team up with Lucas Carey, a biologist, who taught me how to perform wet experiments. This was really exciting. A computer is familiar to me, but I had never worked in a wet lab before."

Tuning the noise
Van Dijk's research at first focused on modelling and simulating stochastic gene expression. His debut in the wet lab consisted of measuring gene expression in yeast. "Our initial idea was to measure single-cell gene expression of a set of genes with sequence differences in their promoters to establish whether and how the promoter sequence influences the variability or noise in gene expression of a certain cell population. Using a computer model we were able to simulate gene expression and subsequently predict how the promoter can suppress 'noise'. A number of our model predictions, we tested in the wet lab by inducing specific DNA mutations in the promoter sequences." Interesting findings that resulted in two papers, one in PLoS Biology and the other in Genome Research. "Both papers deal with 'tuning' the noise in gene expression", van Dijk explains. "We found that gene expression noise is not a constant, but can be very precisely regulated by altering the DNA sequence of the promoter. To us, the eye-opener was that there are multiple strategies to activate a gene to the same expression level, but the resulting noise level showed large differences. Next to the gene expression level itself, is gene expression noise a quantitative value that is encoded in the promoter sequence. Evolution created a 'choice' to enhance gene expression with or without a lot of noise."

Postdoc position
The Weizmann Institute is a great environment for a scientist, says van Dijk. "It is a beautiful and very inspiring place to work. There are a lot of interesting lectures to attend and there are always internationally renowned scientists visiting the institute." No wonder, van Dijk decided to stay longer and thanks to an EMBO scholarship to follow up on his NBIC Travel Grant, he was able to spend almost a year in Israel. "Peter Sloot deserves credit here as well, he was very supportive of my stay at the Weizmann." And right now, he is back there again. "After my visit, Eran Segal offered me a postdoc position, which I gladly accepted! I am already busy with some new exciting projects here. In the future, I would like to set up an academic career back in the Netherlands."

Carey LB, van Dijk D, Sloot PMA, Kaandorp JA, Segal E (2013)
Promoter Sequence Determines the Relationship between Expression Level and Noise.
PLoS Biology 11(4):e1001528. doi:10.1371/journal.pbio.1001528

Dadiani M, van Dijk D, Segal B, Field Y, Ben-Artzi G, Raveh-Sadka T, Levo M, Kaplow I, Weinberger A, Segal E
Two DNA-encoded strategies for increasing expression with opposing effects on promoter dynamics and transcriptional noise
Genome Res. 2013. doi:10.1101/gr.149096.112 Text by Esther Thole.

Chris Lauber wins NBIC Young Investigator Award

Thu, 11 Apr 2013 16:31:00 +0200

Chris Lauber (LUMC) is the winner of the NBIC Young Investigator Award. NBIC yearly presents this award for a young researcher who has significantly contributed to bioinformatics or the bioinformatics community in the Netherlands. Chris was nominated by Sasha Gorbalenya and has been chosen as the winner of the award by NBIC Young Investigator Award Committee. Chris will be awarded with a cash prize of 2.500 Euro funded by NBIC. The award ceremony is planned on April 16th at the Netherlands Bioinformatics Conference NBIC2013 in De Werelt in Lunteren (Ede). The ceremony will be followed by an honorary lecture of 20 minutes by Chris Lauber “On the Evolution of Genetic Diversity in RNA virus species”. During his lecture he will summarize the work in his PhD thesis which is devoted to studying the evolution and genetic diversity of several RNA virus families.

Panter released

Thu, 11 Apr 2013 16:02:00 +0200

Mathijs Kattenberg (VU) has released an Open Source version of Panter to the NBIC software repository. Panter stands for the Persons and Address Informationsystem NTR and provides a user interface to the address and research administration database of the Netherlands Twin Register. The application is written in C# and uses an MS-SQL server as database store. An open source edition is provided via NBIC under the GPLv3 license. The system Panter was designed for studies of extended twin families which are registered with the Netherlands Twin Register, but it is applicable to any longitudinal study involving participants that need to be tracked over longer periods of time. Longitudinal studies need to keep track of a variety of administrative information on their participants: the addresses of participants, the relationships among participants and the participation in various research projects. In a register these changes may be dynamic and can vary over time.

The administrative functions provided by Panter include importing new individuals and families or adding new family members, address management (tracing twins and families who have moved), documenting the participation status of individuals (moved, not willing to participate, ill, deceased), and storing information on questionnaire mailings, responses to mailings and reminders, approaching nonresponders and approaching subjects for other than survey projects, such as biobank studies.

Panter is at its heart extremely flexible in handling persons and relations. Panter has no intrinsic notion of types of relations, for example, biological parents versus stepparents. New relations among participants are easy to add and old relations can be made inactive, still retaining the information on the past existence of this relationship. Selection of subjects can be based on individual characteristics or on relations among participants. Panter was set up to make it easily adaptable for other environments. The solutions built into Panter present a flexible approach to accommodate pedigrees of arbitrary size, multiple biological and nonbiological relationships among participants and dynamic changes in these relations that occur over time, which can be implemented for any type of multigenerational family study. Panter has been designed and built to accommodate new developments in genetic epidemiological research. Typical examples of such developments are increasing data collections, both in sample size and dimensionality, and the need to integrate data in collaborative studies.

In short, Panter facilitates research by offering a smooth handling of administrative processes and unrestricted options for relations among participants. Panter is available via the NBIC repository: https://trac.nbic.nl/panter/

Misty and inspiring Winter School

Fri, 05 Apr 2013 15:31:00 +0200

March 2013 NBIC organized a Winter School in collaboration with the SIB Swiss Institute of Bioinformatics. Nineteen participants from five different nationalities gathered in Kandersteg (CH) for a week of interesting lectures and discussions at the intersection of bioinformatics and medicine. The lectures were very much appreciated, including the contributions from the Dutch teachers as illustrated by the feedback of participants: “very good talkers, especially Frank van Harmelen gave a very inspiring talk on semantic web (which is not that easy)” and “Talking to an expert also from the medical area, Han Brunner, who actually has interactions with patients was a great experience, made things even more interesting.” The social programme on Wednesday included skiing and hiking in the – unfortunately misty – landscape of Switzerland. The NBIC/SIB Winter School is part of the NBIC PhD school aimed at training and education of bioinformatics and life science researchers.

Congratulations to SIB

Fri, 05 Apr 2013 14:49:00 +0200

On March 30, the SIB Swiss Institute of Bioinformatics celebrated its 15th anniversary. NBIC congratulates its colleagues in Switzerland. Since its creation in 1998, the SIB institute has grown exponentially and is now represented by almost 40 groups located within Switzerland’s major Universities and Swiss Federal Institutes of Technology. SIB develops resources used by researchers all over the world and its expertise is requested within the framework of many Swiss and international research projects. Bioinformatics is expanding at a remarkable rate, paving the way to new breakthroughs and promising perspectives, especially in the medical field.

You will find more details in the press release online on the SIB website.

Netherlands hosts first ELIXIR nodes workshop

Fri, 05 Apr 2013 14:38:00 +0200

Representatives of ELIXIR Nodes came together in Noordwijk, Netherlands, for a successful two-day workshop on 21-22 March. The event was organised by NBIC, which is leading the Dutch ELIXIR Node (DTL-DISC).

Over 50 participants came together to discuss several key issues including how each Node planned to respond to the review carried out by ELIXIR's Scientific Advisory Board, which took place in late 2012. Delegates also held fruitful discussions on possible areas of future collaboration between Nodes. The workshop also saw discussions on how industry can be engaged in the development of ELIXIR and what the current interactions were between ELIXIR Nodes and the other ESFRI Biological and Medical Sciences Research Infrastructures.

NBIC NGS course portfolio complete

Tue, 05 Mar 2013 10:13:00 +0100

With the 'Metagenomics Approaches and Data Analysis’ that was held in Leiden recently, the NBIC NGS course portfolio has now reached its completion. The NGS courses form the major component of the Life Sciences (LS) track of the NBIC PhD School. The LS track was initiated by NBIC’s NGS Taskforce and the BioWise programme, and all courses are co-organised with other organisations. The LS Track is targeted at a broad audience of bioinformaticians and life sciences researchers and aims at disclosing the full spread of Next Generation Sequencing (NGS) applications.

The NGS Course Portfolio now consists of:

one basic NGS course (coordinated by LUMC)
4 advanced courses:

RNAseq Data Analysis, co-organised with LUMC and AMC
Genomic Resequencing: Variant Detection and Interpretation in a Diagnostic Context, co-organised with the Centre for Genome Diagnostics (CGD) and UMC Radboud
De novo assembly from NGS data, co-organised with WUR
Metagenomics Approaches and Data Analysis, co-organised with LUMC, UMC Radboud and NIZO Food Research.

In its short life, the advanced NGS courses programme has already attracted 180 participants. Approximate half of the participants are PhD-students in the Netherlands. Others include post-docs, people from industry and hospitals, and many people from abroad. Several NBIC BioAssist programmers have made substantial contribution to these courses: Jeroen Laros and Martijn Vermaat from LUMC, Rutger Brouwer from ErasmusMC, and Jan van Haarst from WUR.

All NGS courses will be provided on a yearly basis. We are also planning to implement new courses (e.g., Epigenomics) based on the request from the academic and industry community. We welcome your suggestions on how to improve or extend our course portfolio. For more information & (pre-) registration for the NGS courses please see the PhD-school on the NBIC website.

Recon 2: Metabolic reconstruction by consensus

Fri, 01 Mar 2013 13:30:00 +0100

Just as all roads lead to Rome, all biological pathways point the focus on metabolism. Studying human health and disease requires thorough understanding of metabolism and as a result, numerous efforts have been dedicated towards metabolic reconstructions that bring together biochemical, genetic and genomic knowledge in a structured manner. Such reconstructions are essential to bottom-up systems biology analyses and enable mechanistic investigations of the genotype-phenotype relationship.

Several global human metabolic reconstructions have been generated, as well as a number of cell-type specific reconstructions. Of the global reconstructions, Recon 1 is probably the most widely used. To make the most of the various reconstructions and to incorporate newly developed metabolic models and data - without duplication efforts - a large group of researchers, including former NBIC PhD student Miranda Stobbe, decided to pool resources and generate a community-driven consensus human metabolic reconstruction using available sources. This has resulted in Recon 2, the most comprehensive human metabolism resource to date. Recon 2 is publicly available at: http://humanmetabolism.org/

Thiele I, Swainston N, et al.
A community-driven global reconstruction of human metabolism
Nature Biotechnology, advanced online publication 3 March 2013, doi:10.1038/nbt.2488

NBIC Young Investigator Award 2013 is looking for nominees

Thu, 28 Feb 2013 16:50:00 +0100

During the NBIC 2013 on April 16, NBIC will present the NBIC Young Investigator Award 2013. The winner will be awarded with a cash prize of 2.500 Euro. The award ceremony is planned on Day 1 of the conference (April 16th, 2013) and will include an honorary lecture by the recipient of the award. You can now nominate candidates (PhD’s). They must meet the following criteria:

The candidate must have conducted his/her research primarily in a Dutch institute.
The primary result on which the award will be based will be the PhD thesis written by the candidate. Therefore, the final version of the thesis of the candidate should have been submitted to the PhD committee at the candidate's university between January 1, 2012 and February 28, 2013 at the latest.

Other criteria that might be considered by the award committee are:

The candidate significantly contributed to the idea of the research;
The research of the candidate resulted in novel or improved bioinformatics methodologies;
The research of the candidate advanced life sciences research;
The candidate independently conducted the research;
The research resulted in a scientific publication, software application or database;
The work of the candidate has given broad visibility of bioinformatics in the life sciences field;
The candidate has otherwise significantly contributed to bioinformatics or the bioinformatics community in the Netherlands.

Each nomination must be accompanied with:

Name and affiliation of candidate
Motivation for nomination by group leader of candidate
Curriculum Vitae of the candidate
A URL to the final version of the PhD thesis (preferably to the PDF of the printed version)

You can submit your abstract via the YIA submission form.

More information about the NBIC YIA at the NBIC2013 website.

Knowledge is like Love

Tue, 26 Feb 2013 09:32:00 +0100

February 25 Barend Mons gave his inaugural speech with the title “Knowledge is like Love..... it multiplies when shared“. In his lecture he described the new field of Biosemantics, and more specifically the methodology of nanopublications. Professor Mons: “Biosemantics is indispensable to understand the complexity of biology. Not because biology is so much more complex than in the past, but simply because we uncover layer after layer of the complexity that was always invisibly there. With the advent of high-throughput technologies in the life sciences we have had a crisis in scientific communication evolving in stealth mode, which is now hitting with full force: an unmanageable amount of relevant data.” With the explosion of information in the biomolecular field, there is a dire need for tools that assist biologists in retrieving, extracting, and relating information and knowledge in the literature and in molecular databases. This will be done in the new field of Biosemantics. Barend Mons was appointed Professor of Biosemantics at the Leiden University Medical Centre, a chair established by NBIC. The Biosemantics group is a structural collaboration between two research groups in Leiden (LUMC) and Rotterdam (EMC) with a focus on in silico knowledge discovery in the life sciences. You can read more in the full text of inaugural lecture Barend Mons.

CIMP, BRAF, FOX

Thu, 14 Feb 2013 15:38:00 +0100

In colon cancer, a subset of tumours called the CpG island methylator phenotype (CIMP) is characterized by high levels of cancer-specific methylation. Associations have been established between CIMP and BRAF mutation, but the underlying mechanisms remain unclear. In attempt to tackle this issue, Eddy van Roon (Erasmus MC Rotterdam) and colleagues, including NBIC Faculty member Judith Boer, studied genome-wide methylation differences between colorectal tumours carrying a BRAF mutation and BRAF wildtype tumours. They succeeded in identifying new BRAF-mutation specific methylation changes in colorectal cancer, including validated differential methylation of forkhead box (FOX) transcription factors. The authors also found methylation-dependent silencing of FOXD3 and enrichment of several cancer-related pathways, including the PI3 kinase and Wnt signalling pathways.

van Roon EH, Boot A, Dihal AA, Ernst RF, van Wezel T, Morreau H, Boer JM
BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer.
Clin Epigenetics. 2013 Jan 16;5(1):2

NBIC2013: Call for Abstracts

Thu, 31 Jan 2013 11:09:00 +0100

The 8th edition of the Netherlands Bioinformatics Conference 2013 (NBIC2013) will be the last edition organized by the NBIC office. We invite you all to join this conference, which is thé place to be when you want to meet senior and junior researchers of the bioinformatics network in the Netherlands. Registration is open now, and you can submit abstracts untill March 4th. Abstract submission
You can submit an abstract for an oral presentation, a poster presentation and for a demo during the application showcase for the NBIC2013 programme. Abstracts can also be submitted for the two satellite meetings: the Metagenomics Satellite track, the NSBM Spring Meeting 2013 and for the parallel Data & Technology session. Submit your abstract via the conference website. Date:         16 & 17 April 2013
Venue:       De Werelt, Lunteren, the Netherlands
Website:    http://www.aanmelder.nl/nbic2013. Programme

5 keynote speakers, a.o. Alexander van Oudenaarden, Janet Thornton, Uwe Sauer, Roeland van Ham and Jeroen Raes
Satellite meetings: Spring meeting of the Netherlands Society on Biomolecular Modelling (NSBM) & Metagenomics Satellite Track
Parallel sessions of contributed lectures
Parallel workshops
Poster presentations
Industry meeting (BIUP)
RSG Retreat on April 15th

Key dates

deadline for abstract submission Monday March 4, 2013
notification of selection for oral presentations: Friday March 22, 2013
registration deadline: April 1, 2013

About NBIC2013
The Netherlands Bioinformatics Conference 2013 (NBIC2013) is the 8th edition of the annual conference organized by the Netherlands Bioinformatics Centre (NBIC). NBIC2013 discusses the latest developments in bioinformatics and interrelated disciplines, and their wide-ranging applications in life sciences & health, agriculture, food & nutrition and industrial biotechnology. NBIC2013 offers a cross-disciplinary scientific program of (poster) presentations, application demonstrations and workshops, as well as other opportunities to exchange innovative ideas.

More information
Contact: Femke Francissen, e-mail: femke.francissen@nbic.nl

Call for proposals - NWO TOP Grant

Thu, 31 Jan 2013 11:06:00 +0100

The Board of NWO Physical Sciences (GB-EW) invites researchers with an interest in astronomy, computer science and mathematics to submit proposals for a TOP grant. TOP Grants are intended for applications involving innovative and risky scientific research which addresses a question of a high academic standard and great scientific urgency. Applications should have demonstrable importance for astronomy, computer science and/or mathematics. The TOP scheme is divided into two modules: one for senior researchers and one for junior researchers. More information on the NWO website.

Bioinformatics in the movies

Fri, 25 Jan 2013 14:29:00 +0100

Bessensap, the yearly “science and press” event organized by NWO offers the opportunity to make a video about your research results, method or equipment. If you would like to make use of this opportunity you should pitch your idea in a 60 second video (made by your mobile phone) before March 4th. All the pitched ideas will be available online and distributed through social media. The top five ideas will be selected for a 5 minutes professional video, which will be shown on the Bessensap event in June this year. So, grap you smart phone and tell the world in 60 seconds why your bioinformatics application is the best! More information on the website of Bessensap (in Dutch).

SARA & NBIC collaborate in the cloud

Mon, 21 Jan 2013 11:40:00 +0100

During NBIC's de novo Assembly course in Wageningen this January, all practicals were carried in SARA's HPC cloud, with great success! All 42 participants were running jobs concurrently both on individual Virtual Machines with pre-installed software for the course and on the NBIC Galaxy server (also in the SARA cloud). Operation was smooth and flawless as was acknowledged by teachers and participants, who were hardly aware of the special environment as one wrote “Computers worked very well!”. A big “thumbs-up” for SARA cloud support! SARA and NBIC plan to further expand this collaboration in training, a.o. in the context of DTL-DISC.

NBIC's flying course circus

Mon, 21 Jan 2013 11:31:00 +0100

On January 8^th-9^th, the first NBIC course of this year was held in Wageningen. 42 (!) participants from the Netherlands and some neighbouring countries visited the first issue of the “de novo Assembly from NGS data” and learned how to juggle with heaps of NGS data. Over 90% of the participants said they could apply what they've learned in their research: “Very informative and useful”! This week, from January 21^st till 25^th, the second NBIC course of this year, “Pattern Recognition” is running in Amsterdam. Participants will learn how to perform the most intricate tricks with high volume life sciences data. This course will be followed shortly by the “Metagenomics approaches and data analysis” course in Leiden on February 6^th-8^th, focussing on the analysis of sequence data from whole ecosystems. Some seats are still available! Please register if you would like to participate!

Metagenomics popular amongst high school teachers

Fri, 18 Jan 2013 16:26:00 +0100

Together with foundation Leve DNA! and high school Kandinsky College in Nijmegen, NBIC is trying to make metagenomics accessible for other high schools. In this project two pupils have taken samples from the Waal river. Leve DNA! has sequenced the 16s rRNA in these samples. NBIC and two teachers of the Kandinsky College are now developing educational material based on these results. A first teacher workshop on this subject was held on January 12 during the NIBI-conference for biology teachers. Participants got to know what metagenomics is and how they can analyze the results with MG-RAST. All 20 teachers were very enthusiastic about this new field of research and eager to try it in class with their students.

BioCafé and Course

Thu, 10 Jan 2013 14:55:00 +0100

RSG Netherlands, the network of junior researchers in bioinformatics, invites you for the Bio-Café on 21st January, 2013 in Amsterdam. The Bio-Café includes a contest which challenges your bioinformatics and general knowledge. Registration by e-mail is required.

The Bio-Café is part of the social programme of the Pattern Recognition course organised by the NBIC PhD school January 21-25, but also open for junior researchers who are not participating in the course. There are still some seats available for the course! You can register through the enrolment form.

Changed access to national e-infrastructure

Fri, 21 Dec 2012 13:59:00 +0100

Many bioinformatics researchers in the Netherlands have become familiar with the BiG Grid e-Infrastructure over the past six years. The access to the e-Infrastructure (grid, cloud, hadoop, etc.) has been organized through the BiG Grid project. SARA, Nikhef, CIT-RUG and Philips Research have been instrumental in operating the e-Infrastructure and providing various kinds of support to researchers. The BiG Grid project ends at 31 December 2012 and you can read the project achievements in the stories (in Dutch) of users at the BiG Grid website. SARA, which is expected to be part of SURF from January 2013, will be responsible for the e-Infrastructure from January 1, 2013. At Sara’s website is briefly explained the most important changes for researchers who want to apply for access to the national e-infrastructure, including the application procedure. As of 1 January 2013 SARA will be part of the SURF Foundation. From that date on SARA will carry a new logo and a new name: SURFsara. The services and accompanying support for science and industry from their location in Amsterdam will continue without changes. The website www.sara.nl will be moved to www.surfsara.nl. People at SURFsara can be reached through an email address with surfsara.nl, but the sara.nl addresses will temporarily stay available.

The aim of the merger is to achieve greater synergy within the national e infrastructure by making it part of a single organisation (SURF). The merger will above all benefit researchers at higher education and research institutions. Scientific research nowadays involves both an increasing need for large modelling and simulation and an increasing number of large and complex datasets. This ‘Big Data’ demands large-scale computing capacity, extensive data storage facilities, visualisation facilities and high-quality user support, combined with advanced network facilities. The combination of facilities created by the merger will provide for all this on a long-term basis.

Metagenomics Research of Skin Bacteria in public media

Fri, 14 Dec 2012 13:43:00 +0100

The results of metagenomics research of bacteria on human skin have reached the editors of the popular news website NU.nl (in Dutch) and the newspaper BioNieuws. Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin in healthy volunteers. Skin injury will disturb the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. A recent paper in Genome Biology of Zeeuwen et al describes the analysis of the microbiota of the surface layer and the deeper layers of normal skin. The authors from the UMC St Radboud, NIZO food research and Wageningen University, including NBIC Faculty Sacha van Hijum, investigated the dynamics of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury. The results of this study could in the future help in more accurately predicting the wound healing process based on host factors and the microbiome of deeper skin layers. Patrick LJM Zeeuwen
Microbiome dynamics of human epidermis following skin barrier disruption
Genome Biology 2012, 13:R101 doi:10.1186/gb-2012-13-11-r101

Apply now for funding for PCDI Postdoc Retreat 2013!

Fri, 14 Dec 2012 13:23:00 +0100

The Postdoc Career Development Initiative (PCDI) supports postdocs and final year PhD students at career orientation and realizing young researchers’ potential. On 13 - 15 March 2013, PCDI’s best known event, the annual Postdoc Retreat, will be held for the 9^th time. Aim of this three-day course is to support you in making the next step in your career: identify your skills and talents, develop a vision on science, improve your transferable skills and learn about the variety of career paths in Life Sciences within and outside academia. The programme includes inspiring lectures, training workshops, meet & greet with potential employers and a forum discussion with prominent persons in Life Sciences. The PCDI Postdoc Retreat is a unique career development course in the Netherlands. As it is exclusively open to postdocs and final year PhD students in Life Sciences, you can expect tailored activities, immediately relevant to your career stage. Over 900 early career scientists already took part in the PCDI Postdoc Retreat, including more than 85 participants from NGI-centres. Funding for 50 NGI postdocs/PhD students to attend
The Netherlands Genomics Initiative wants to actively encourage her young researchers to participate. NGI will sponsor participation for the very last time, up to a maximum of 50 sponsorships of the registration fee (max 5 per centre). This NGI funding will be assigned on a first come first served basis. NGI sponsored participants of earlier editions of the PCDI Postdoc Retreat cannot reapply for NGI funding for 2013. NBIC is one of the NGI Centres. If you want to make use of this opportunity to apply for a NGI-sponsored seat, please fill out the registration form attached and mail it to hegge@genomics.nl. Before sending, it should also be signed by the director of the NGI Centre (Ruben Kok for NBIC). Registration closes on 19 February 2013 or whenever the maximum number of participants has been reached. So register NOW!

Inken Wohlers (CWI) defended thesis on protein structure comparison

Thu, 13 Dec 2012 16:17:00 +0100

CWI researcher Inken Wohlers from the group of Gunnar Klau has developed mathematical models and computer algorithms to compare two protein structures optimally according to given criteria. Because of their complex structure, comparing proteins accurately is difficult. There are many criteria that can be used to compare proteins, leading to a myriad of different computer algorithms and methods that are currently in use. The general frameworks presented in Wohlers' thesis incorporate existing criteria as well as novel criteria and calculate an optimal solution based on that. Exact algorithms for pairwise protein structure alignment
Inke Wohlers
http://dare.ubvu.vu.nl/handle/1871/39301

Groningen and Chromosome 5

Thu, 13 Dec 2012 15:40:00 +0100

The Chromosome Centric Human Proteome Project (C-HPP) has the goal to detect and catalogue protein gene products and link them to their original chromosome location. C-HPP is organized teams for each chromosome with participation of world leading proteomics and bioinformatics laboratories. The Analytical Biochemistry group at University of Groningen headed by Rainer Bischoff was recently invited to join the C-HPP initiative taking responsibility for Chromosome 5. The Chromosome 5 team is further supported by Dirkje Postma’s (UMCG) group, which is internationally leader in COPD, asthma and lung cancer research, Manfred Wuhrer’s research group (LUMC, VU) which has extensive glycoproteomics expertise and the group of Henry Lam (HKUST, Hong Kong) with considerable bioinformatics expertise.

Pig genome reveals genes that made domesticated pigs longer

Thu, 06 Dec 2012 14:33:00 +0100

Since having been tamed and domesticated some ten thousand years ago, pigs have been getting longer. Researchers from the universities of Wageningen, Uppsala, Copenhagen and Edinburgh and led by professor Leif Andersson (Uppsala University) and NBIC faculty member professor Martien Groenen (Wageningen University) published details of the genetic origins of this remarkable change in an article in PNAS (Proceedings of the National Academy of Science).

The PNAS paper was simultaneously published with the Nature article about the sequencing of the pig genome. On November 15^th the international ‘Swine Genome Sequencing Consortium’ published their findings of the swine genome in Nature. The consortium was headed by Prof. Martien Groenen from Wageningen University, Prof. Larry Schook from the University of IIlinois and Prof. Alan Archibald of the University of Edinburgh. The swine genome is an important milestone research on pig evolution, pig breeding and due to the similar physiology of the pig with humans also as a model for biomedical research.

Rubin et al.
Strong signatures of selection in the domestic pig genome
Proc. Natl. Acad. Sci. USA, 15 November 2012

Groenen et al.
Analyses of pig genomes provide insight into porcine demography and evolution.
Nature 491:393-398

Galaxy on cloud

Thu, 08 Nov 2012 11:54:00 +0100

Collaboration between NBIC and the e-BioGrid team resulted in a new service: NBIC Galaxy on Cloud. The migration of Galaxy to the cloud allows end-users (bioinformaticians, biologists or clinical researchers) to run their Galaxy tools and workflows on the BiG Grid High Performance Computing (HPC) cloud at SARA. The Dutch cloud version of Galaxy enables processing of big data volumes and the high speed network connection provides rapid data transfers.The application scales dynamically with increasing workload.

The NBIC Galaxy is used for genomics and proteomics data analysis. End users can easily use the web based interface to run sophisticated methods and algorithms without worrying about the local installation, maintenance, or data backups. Various NBIC BioAssist teams are also using this service to collaborate and provide integrated data analysis pipelines to end users in the life sciences and other national programme’s like the Netherlands Proteomics Centre and Ecogenomics centre.

The NBIC Galaxy on cloud is suitable to run complicated genomics and proteomics data analysis algorithms and it can deal with large amounts of data like de novo assembly task of middle to large genomes. In addition, the NBIC Galaxy support team and the BRS-team, can help end- users from non-commercial parties to do better science by allowing them to explore and analyse their full datasets on the server in a consistent manner. Furthermore, life scientists can be trained on this server during the Galaxy and Sequencing courses to work with state-of-the-art datasets and tools.

For more information, please send a mail to nbicgalaxy-admin@trac.nbic.nl

VarioML: lightweight option for variation data

Thu, 08 Nov 2012 11:42:00 +0100

In the global effort to unify genetic variation databases, covering human and model organism data, many obstacles still have to be scaled. Integrating data from the numerous different databases is difficult due to the lack of a single standard. Instead of trying to design a unifying format in a top-down manner, a large group of international variant experts, including NBIC Faculty member Morris Swertz (University Medical Centre Groningen) opted for a lightweight framework that allows users to compose interoperable use-case specific micro-standards around a limited number of generalized concepts. The group specifically focused on improving data entry into and data exchange between locus-specific databases (LSDB), of which currently more than 4,000 are around. Their efforts resulted in VarioML, which allows researchers, clinics and diagnostic laboratories to share human variation data in a straightforward and unambiguous manner. The open-ended nature of VarioML ensures that future extensions and adjustments can easily be incorporated.

Byrne MG, et al.
VarioML framework for comprehensive variation data representation and exchange
BMC Bioinformatics 2012, 13:254

Duplicates are not the same (anymore)

Tue, 06 Nov 2012 10:57:00 +0100

Gene duplication is a common phenomenon and plays as important role in evolution, because after duplication, the resulting paralogs each go their own way. They accumulate different mutations and start to exhibit differences in expression patterns. To find out more about the extent of divergence between paralogs and to study the influence of epigenetic modifications on this process, Lidija Berke and colleagues from Utrecht University focused on the role of the epigenetic mark H3K27me3 on the evolution of gene expression patterns in the model plant Arabidopsis thaliana. The results show an association between H3K27me3 (trimethylation of histone H3 at lysine 27) and the extent and manner of divergence between paralogs. Paralogs that are both targeted by H3K27me3 exhibit low expression levels, but a high coding sequence divergence. In contrast, pairs in which only one gene is targeted by this mark show the highest divergence in expression patterns and upstream regulatory sequence. Particularly for transcription factors, the difference in expression patterns is pronounced. According to the authors, this analysis demonstrates the importance of epigenetics in the evolutionary fate of genes.

Berke L, Sanchez-Perez GF, Snel B.
Contribution of the epigenetic mark H3K27me3 to functional divergence after whole genome duplication in Arabidopsis
Genome Biology 2012, 13:R94

Tool: CLI-mate

Tue, 23 Oct 2012 09:14:00 +0200

To inform as many people as possible about the large list of bioinformatics tools available, we will monthly present a tool in the news. This month we put the spotlight on CLI-mate. CLI-mate is a service to facilitate developers in creating user-friendly interfaces for a command line tool. CLI-mate was developed at the Department of Human Genetics, Leiden University Medical Center (LUMC). In the agile development environment of bioinformatics, many command line tools are created quickly to fill in gaps between complex information processes. A command line interface (CLI) is sometimes sufficient for the task, but it limits adoption by a broader audience. Therefore it’s often necessary for the developer to create a wrapper that provides a more user friendly interface. The CLI-mate interface generator makes this easy: it can generate different wrappers: one of them is turning the program into a Galaxy tool.

TNO and Sanquin in NBIC consortium

Thu, 11 Oct 2012 16:43:00 +0200

The NBIC consortium has been extended with two new partner organisations: TNO and Sanquin. TNO is an independent research organisation whose expertise and research make an important contribution to the competitiveness of companies and organisations, to the economy and to the quality of society as a whole. TNO’s unique position is attributable to its versatility and capacity to integrate this knowledge. Sanquin Blood Supply Foundation ensures the safe and efficient blood supply in the Netherlands. Sanquin also develops and produces pharmaceutical products, conducts high-quality scientific research, and develops and performs a multitude of diagnostic services.

The power of combining

Tue, 09 Oct 2012 08:55:00 +0200

Being able to predict the clinical outcome in individual breast cancer patients is essential to ensure each patient gets the right therapy (and is spared unnecessary treatment). Both clinical data and gene expression data are used to derive predictors of clinical outcome. However, combining the two sources to build a single prediction model remains rare and the few examples where it has been tried have yielded inclusive results on prediction performance. Together with colleagues from the Netherlands Cancer Institute and the Academic Medical Centre Amsterdam, Martin van Vliet (Delft University of Technology) performed an extensive comparison of three integration strategies as well as using five classifiers of varying complexity without integration data types. They used a dataset of breast cancer samples of which both gene expression profiles and clinical data are available to develop predictors, which were subsequently validated using four independent breast cancer datasets. Their main conclusions are that combining the two data types increases the performance of all five classifiers and that the late OR integration strategy generates the best overall result of the three strategies tested. van Vliet MH, Horlings HM, van de Vijver MJ, Reinders MJ, Wessels LF
Integration of clinical and gene expression data has a synergetic effect on predicting breast cancer outcome.
PLoS ONE 7(7): e40358. doi:10.1371/journal.pone.0040358

EBI Roadshow 2013 hosted by Amsterdam and Maastricht

Mon, 08 Oct 2012 10:26:00 +0200

Together, Antoine van Kampen (AMC), Chris Evelo (UM) and Celia van Gelder (NBIC) have successfully applied for hosting 5 days of EBI Roadshow modules in early summer 2013. Maastricht University will host 3 days covering Ensembl, interactions & pathways and small molecules in bioinformatics (a.o. ChEMBL). The other 3 days are hosted by the Academic Medical Centre (AMC) in Amsterdam, covering Introduction to databases, Sequence Alignment, Ensembl and ArrayExpress. If you are interested in a specific module or topic please mail to education@nbic.nl to be put on a pre-registration list.

Biobank Life Lines in 8 o’clock news

Fri, 05 Oct 2012 16:04:00 +0200

LifeLines, the biobank and multidimensional cohort study developed by UMC Groningen, got the attention of the 8 o’clock news (NOS journal). Morris Swertz, NBIC Faculty and PI of the BioAssist Biobanking taskforce, is involved in this project. LifeLines has become one of the most valuable public, multidimensional cohort studies and biobanks in the world. LifeLines offers a unique data resource to study a broad scope of (epi)genetic, biomedical, environmental and psychosocial factors in relation to healthy ageing, disease development, and general well-being.

3rd NBIC Pattern Recognition Course: Registration open now!

Fri, 05 Oct 2012 15:26:00 +0200

On January 21-25 2013, the 3^rd edition of the Pattern Recognition course of the NBIC PhD school will take place in Amsterdam. Perry Moerland has taken over the coordination for this course from Dick de Ridder, who has organized the 1^stand 2^nd edition of this course in Delft in 2009 and 2011. The course introduces theory and tools from the fields of pattern recognition and machine learning to solve bioinformatics problems. After the course, you have an overview of basic pattern recognition techniques and are able to recognize what method is most applicable to classification problems you will encounter. Registration is open now! You can register through the enrolment form.

SIB Fellowship program: Call for applications

Tue, 02 Oct 2012 09:47:00 +0200

The SIB Fellowship program aims to train outstanding bioinformatics PhD students as well as promote bioinformatics research for the life sciences.

The SIB Swiss Institute of Bioinformatics, thanks to the generous support and trust of its partners*, is offering the opportunity to a selection of the best students worldwide to carry out their PhD research in one of its groups, all of which are located across Switzerland. The laureates will receive a financial grant for 3 years (extendible for 1 year) and:

Become a member of SIB, the leading network of Swiss bioinformatics
Have access to professional training courses
Be part of the Swiss PhD Training Network in bioinformatics
Be introduced to industrial partners during specific events
Participate in SIB events such as the yearly SIB Days (scientific conference)
Attend the Summer School and Students’ Retreat
When in collaboration with industry, have direct hands-on experience within that company

SIB provides core databases, software and support for the worldwide life science research community. It leads and coordinates the field of bioinformatics in Switzerland by federating bioinformatics research groups from Swiss schools of higher education and research institutes. Currently, SIB consists in 38 research and service groups located in the country’s seven main cities. SIB creates, maintains and distributes world-renowned bioinformatics resources, mainly free of charge, to the national and international life science research community. A few examples include UniProtKB/Swiss-Prot, STRING, SWISS-MODEL, SwissDock and neXtProt.

Key dates of the SIB Fellowship program:

Closing date for applications:15 November 2012
Shortlist selection announcement:10 December 2012
Interviews: January/February 2013
Start of PhD: September 2013

Further information and application forms for the SIB Fellowship program are available at www.isb-sib.ch/fellowship.

*) SIB Partners: King Abdullah International Medical Research Center, the Leenaards Foundation, the Swiss Foundation for Excellence and Talents in Biomedical Research, SystemsX.ch and the University of Lausanne.

Maastricht UMC+ partner in NBIC consortium

Thu, 27 Sep 2012 16:57:00 +0200

Maastricht UMC+ signed the partner agreement with NBIC and became partner in the NBIC consortium. Maastricht UMC+ is the name of the collaboration between the Academic Hospital Maastricht (AzM) and the Maastricht University. Research of Maastricht UMC+ takes place in five research schools: Caphri (Public Health & Primary Care), CARIM (cardiovascular diseases), GROW (oncology & development biology), MHeNS (mental health & neurosciences) and NUTRIM (Nutrition, Toxicology and Metabolism). Maastricht UMC is the 8th University medical Centre in the NBIC Consortium.

Dairy details

Mon, 17 Sep 2012 09:23:00 +0200

For those who are familiar with the strong and mostly unpleasant odour of sulfur-containing compounds, it may come as a surprise that such compounds are also the source of many of the characteristic flavours of much-loved fermented dairy products like cheese and yoghurt. Important flavour components such as dimethyl sulfide (DMS) and methanethiol are formed during the fermentation process when lactic acid bacteria break down the sulfur-containing amino acids cysteine and methionine.

To the dairy industry, insight into the regulation of this degradation process may offer clues to a rational control of flavour profiles of dairy products. To this end, Mengjin Liu (FrieslandCampina Research) and colleagues from academia including NBIC Faculty members Roland Siezen and Christof Francke, performed a genome-wide in silico analysis to systematically evaluate the regulatory interactions that control the expression of genes associated with cysteine and methionine metabolism in all sequenced species of the order Lactobacillales. The results suggest that the reaction network can be subdivided into five modules, with the family Streptococcaceae appearing to have a distinctly different modular composition compared to the three other families. The authors propose to include the reaction network built on their analysis into a quantitative metabolic network model, in order to develop rational strategies towards flavour control strategies in fermented food products.

Liu M, Prakash C, Nauta A, Siezen RJ, Francke C
Computational analysis of cysteine and methionine metabolism and its regulation in dairy starter and related bacteria.
J Bacteriol. 2012 Jul;194(13):3522-33

PropSeg: determining copy number alternations

Tue, 11 Sep 2012 09:18:00 +0200

Copy number alternations (CNAs) frequently occur in cancer and therefore tools that allow detection of (recurrent) CNAs are of high interest to cancer researchers. Originally developed to detect single nucleotide variants (SNVs), capture sequencing has proven its worth in deriving gene copy numbers as well. To assess changes in copy numbers from capture sequencing data, most approaches rely on determining log-ratios between test and control samples, but these methods are not well suited to deal with the large variety in coverage that is inherent to sequence data, resulting in information loss. These ratio-based approaches also suffer from outliers and are unable to handle homozygous deletions. Guillem Rigaill (Netherlands Cancer Institute, Amsterdam) and colleagues in the group of NBIC Faculty Lodewyk Wessels propose a proportionality model, in which the test sample coverage is modelled as a linear function of the control sample. A major advantage of this new statistical approach is that completely deleted regions are no longer ignored in the analysis. They tested their approach by determining the copy numbers for a set of 600 genes from nine breast cancer cell lines. The new method, called PropSeg, outperformed other log-ratio based methods, while demonstrating high concordance with SNP array results. The code for the new algorithm is available from http://bioinformatics.nki.nl/ocs

Rigaill GJ, Cadot S, Kluin RJC, Xue Z, Bernards R, Majewski IJ and Wessels LFA
A regression model for estimating DNA copy number data applied to capture sequencing data
Bioinformatics 2012, Jul 13

New tool: PhenoLink

Mon, 27 Aug 2012 10:02:00 +0200

In the ongoing quest to understand the relationship between genotype and phenotype, being able to quickly prioritize and visualize potential links and relations has become a true survival skill for those who are taking on the very large and very noisy ~omics datasets to dig for well hidden treasures. To support these efforts, Jumamurat Bayjanov and colleagues (CMBI, Radboud University Nijmegen Medical Centre) have developed PhenoLink, a web-tool that effectively deals with high noise levels and imbalances in phenotype data. PhenoLink can be used on a wide variety of ~omics data. Identified links are visualized, which facilitates prioritizing these links as well as finding relations between features and between phenotypes, and identifying outliers in phenotype data. The authors applied PhenoLink on a set of 42 Lactobacillus plantarum strains to identify relationships between the presence/absence of genes and phenotypes defined by sugar utilization and nitrogen-dioxide production. In addition to known relationships, PhenoLink generated novel gene-to-phenotype relations in a well-studied strain (L. plantarum WCFS1).

Bayjanov JR, Molenaar D, Tzeneva V, Siezen RJ, van Hijum SA
PhenoLink--a web-tool for linking phenotype to ~omics data for bacteria: application to gene-trait matching for Lactobacillus plantarum strains.
BMC Genomics 2012;13:170

‘Distiguished’ Scientist Siezen visits UC Davis, California

Mon, 27 Aug 2012 09:39:00 +0200

Roland Siezen of the Bacterial Genomics group at the CMBI (UMC St. Radboud) in Nijmegen will visit the Food Science and Technology Department of the University of California, Davis, USA. Host scientist will be Dr. Maria Marco. Roland Siezen will be accompanied by NBIC PhD student Lex Overmars of the CMBI, Nijmegen. You can follow Roland and Lex by reading their blog. The visit is part of the Distinguished Visiting Scientist stipend has been awarded by NGI-NBIC to Prof. Dr. Roland Siezen for the period 2010-2013. He will visit international host institutes to set up new collaborations in genomics and bioinformatics of food- and health/disease-related bacteria, in particular in relation to microbial diversity. This will also involve exchange and developments of bioinformatics tools and databases. These host institutes at universities in South Africa and USA are of high international reputation, with excellent scientific infrastructure and computational facilities.

Gunnar Klau Extraordinary Professor at VU University

Fri, 17 Aug 2012 14:11:00 +0200

NBIC Faculty Gunnar Klau is instated as Extraordinary Professor of Bioinformatics and Operations Research at VU University Amsterdam. The appointment is shared between the Faculty of Sciences (Bioinformatics) and the Faculty of Economics and Business Administration (Operations Research). Prof. dr. ing. Gunnar W. Klau is group leader at the Centrum Wiskunde & Informatica (CWI), since 2008. Throughout his career, Dr. Klau has devised problem solving algorithms, using advanced techniques from Operations Research, often in combination with other areas from applied mathematics, thus making fundamental contributions to the area of bioinformatics. You can read more about this news on the website of CWI.

New tool: GO-Elite

Thu, 16 Aug 2012 13:38:00 +0200

Alexander Zambon (UC San Diego) and colleagues, including NBIC Faculty member Chris Evelo, have developed a new tool to perform over-representation analysis on structured ontology annotations, pathway databases or biological IDs. Numerous over-representation tools are already available, but many of these are limited in scope, lack interchangeability or quickly become outdated because they are linked to only one resource. GO-Elite provides users with a flexible pathway analysis tool that uses the relationships between pathways, ontology species and gene ID systems to generate a minimally non-redundant set of results. Results from GO-Elite can be visualized on WikiPathways or as networks. GO-Elite is available as a web interface, GenMAPP-CS plugin and cross-platform application.

Zambon AC, Gaj S, Ho I, Hanspers K, Vranizan K, Evelo CT, Conklin BR, Pico AR and Salomonis N
GO-Elite: a flexible solution for pathway and ontology over-representation
Bioinformatics 2012 28(16):2209-2210 For more bioinformatics tools, please check the NBIC tools list.

Tight leash on ammonia

Thu, 16 Aug 2012 13:31:00 +0200

In low-GC Gram-positive bacteria four regulators, GlnR, TnrA, GltC and CodY, manage the transcriptional control of the enzymes involved in central nitrogen metabolism. Based on an extensive analysis of the genomes of all species belonging the class Bacilli, which includes well-known families such as Bacillaceae, Lactobacillaceae and Staphylococcaceae, Tom Groot Kormelink (Kluyver Centre for Genomics of Industrial Fermentation) and colleagues found that the GlnR regulon is the most constant of the four. Furthermore, GlnR appears unaffected by the absence/presence of the other three regulators. According to the authors, constraining the import of ammonia- and amino-containing compounds is primarily regulated by GlnR, as is the production of intracellular ammonia. Tight control of ammonia levels is important to limit futile cycling by diffusion of ammonia out of the cell, which fits with the proposed role of GlnR, the authors state.

Groot Kormelink T, Koenders E, Hagemeijer Y, Overmars L, Siezen RJ, de Vos WM, Francke C
Comparative genome analysis of central nitrogen metabolism and its control by GlnR in the class Bacilli.
BMC Genomics 2012, 13:191

Disagreeing databases

Tue, 14 Aug 2012 12:08:00 +0200

For those studying metabolism, pathway databases have become essential resources as they bring together the still expanding amount of information on metabolic networks. The number of available databases is increasing, but unfortunately the level of agreement between databases on a particular network or pathway is surprisingly low. For example, a comparison of 5 pathway databases that describe the human metabolic network revealed agreement on only 3% of the reactions described. As information from databases is used by researchers to for example, interpret their findings or design new experiments, mistakes easily propagate.

To shed some light on the causes of this lack of consensus, Miranda Stobbe (Academic Medical Centre, Amsterdam) and colleagues took the well-known and much studied TCA cycle as their reference point. They compared the description of the TCA cycle as provided by 10 human metabolic pathway databases. To their surprise, they found that none of these databases offered an entirely correct description, that is: a description that agrees on all aspects with the available literature. Furthermore, between these 10 databases, consensus exists on only 3 reactions. The authors combine their analysis of the databases with an extensive literature study to come up with an improved description of the TCA cycle in the WikiPathways database. They point to differences in the way databases retrieve information and in the curation process as potential sources for the inconsistencies found. However, it should not be ignored that part of the problem may be that the biochemistry of the TCA cycle, in spite of decades of intensive study, is simply not as clear-cut as previously thought, the authors add in their discussion.

This project is part of the NBIC BioRange I program.

Stobbe MD, Houten SM, van Kampen AH, Wanders RJ, Moerland PD
Improving the description of metabolic networks: the TCA cycle as example.
FASEB J. 2012 Jun 1

Veni and Vidi

Fri, 10 Aug 2012 09:19:00 +0200

July 2012, Jeroen de Ridder (Delft University of Technology) received a Veni grant for the proposal “Searching for new disease genes”. De Ridder will use the Veni grant to study a new analysis technique - based on scale space, a concept from image processing - in order to distinguish important mutations in tumours from unimportant ones. A Vidi was granted to Patrick Kemmeren (University Medical Center Utrecht), to study the regulatory circuits of genetic interactions. Veni and Vidi are part of NWO's prestigious Talent Line programme, which offers scientists at various stages in their career the possibility to do ground-breaking research. On the NWO website you can find:

Pump your career

Mon, 06 Aug 2012 14:27:00 +0200

Diversity is vital for science. The Netherlands Organisation for Scientific Research (NWO) and the Dutch Network of Women Professors (LNVH) are therefore organising a special talent day "Pump your career" to help female scientists with their academic career and to increase the progression of female scientists in academia.

During Pump Your Career female scientists can follow workshops, make acquaintance with role models, obtain information about applying for grants and, of course, network with each other. NWO and LNVH hope to welcome about 500 women. For who?

Women working in science (postdocs, and assistant/associate/full professors)
(University) policy officers who are involved in policy on women

When and where?

11 October 2012 in the Beurs van Berlage, Amsterdam

On the NWO-website you can find more information and a link to the registration form (in Dutch).

Individual pathways, similar response

Thu, 12 Jul 2012 16:48:00 +0200

For many organisms, glucose is the primary source of carbon and of energy. The availability of cellular glucose drives many key biological processes, including growth and metabolism. Even in simple organisms like yeast, the glucose regulatory system has evolved into a complex network of monitoring glucose levels and relaying information to relevant mechanisms in metabolism and gene expression. Although glucose regulation has been studied extensively with yeast (Saccharomyces cerevisiae) as a model organism, a detailed view on how the various pathways are connected, the pathways' underlying hierarchy and the contribution of individual components is still lacking.

Eva Apweiler (UMC Utrecht) and colleagues generated gene expression profiles of DNA deletion mutants under high glucose growth conditions and subsequently used the data to relate the deleted gene to all transcripts that exhibited a significant change in response to the deletion. Overall, their analysis shows that the glucose signalling pathways in yeast are highly interconnected. As a result, disruption of any individual pathway leads to one main transcriptional response that mimics either a high or a low glucose response. This response appears to be mainly mediated by regulation of the biosynthesis of storage carbohydrates.

Apweiler E, Sameith K, Margaritis T, Brabers N, van de Pasch L, Bakker LV, van Leenen D, Holstege FC, Kemmeren P
Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis
BMC Genomics 2012, 13(1):239

Barend Mons appointed as professor at LUMC on behalf of NBIC

Tue, 10 Jul 2012 16:01:00 +0200

Dr. Barend Mons, scientific director of NBIC, has been appointed as professor in Biosemantics at the Leiden University Medical Center. The chair is established by the Netherlands Bioinformatics Centre (NBIC).

Mons: “I feel honored with this appointment, not only for me personally, but also because it is the acknowledgment of the growing impact of the fledgling discipline of Biosemantics. This recognition will also serve the adoption of the semantic web approach to knowledge exchange and discovery in the international arena and it signifies the leading role of Dutch researchers in this field. I feel very privileged to work with all the wonderful and pioneering people in the Biosemantics groups”.

The Biosemantics group is a structural collaboration between two research groups on this topic in Leiden (LUMC) and Rotterdam (EMC). The groups focus on “in silico knowledge discovery” in the life sciences. The Rotterdam group is medically oriented and the Leiden group is more focused on basic human genetics. The overall aim is to structure data and information into computer readable formats (in silico), in order to reason over multiple big data sets and to recognize novel patterns (knowledge discovery).

Examples of computer readable structured data formats are Concept Profiles, Knowlets and Nanopublications. Recently, The Value of Data, a visionary paper proposing a next generation data-publishing model in Nature Genetics had been published by Mons et al. The approach is championed by one of the major projects of the Innovative Medicines Initiative (IMI) called Open PHACTS. A start has been made with the Concept Web Alliance to set up an international nanopublication sandbox database, called: the ‘nanopub’.

Ruben Kok, managing director of NBIC: “NBIC has established this chair in Biosemantics, because the discipline will be crucial for ‘reading’ and interpreting the growing amount of life science data”. Furthermore the semantic web approach pioneered by the Biosemantics group and the Concept Web Alliance in which NBIC is involved in a leadership role will be crucial in the wider field of semantic interoperability of data for many other purposes that those of the Biosemantics research groups. The technology is essentially discipline-neutral and can be used across the ‘red’, ‘green’ and ‘white’ sectors in biology and even beyond life sciences. Hence this will be a crucial field to include in the developments of DTL and DISC.

Insight into Leukemia and Bloodtransfusion

Mon, 09 Jul 2012 13:22:00 +0200

A NWO Free Competition grant is awarded to Anton Feenstra for a project that uses theoretical methods to get insight into Leukemia and Bloodtransfusion.

Leukemia is caused by disruption of the cell division and differentiation of blood stem-cells. A complex network of genes that regulate each other, but also many other genes, normally ensures that this process is conducted in an orderly manner. Applying powerful modelling and analysis methods from theoretical computer science provides better understanding of how this network of genes functions. This insight allows medical reseracher to develop better treatment of leukemia, and enables safer and cheaper blood transfusion.

The project awarded with the NWO-grant is a collaboration between the groups of Bioinformatics (Feenstra, Heringa, Bonzanni) and Theoretical Computer Science (Fokkink, Bonzanni) of the VU in Amsterdam. They will work with the groups of Receptor Biochemistry (Martine Smit, VU Faculty of Science, Chemistry) and Bertie Göttgens (Cambridge Institute for Medical Research) for the experimentally verification of predictions from the models.

A yeast top-model sequenced

Fri, 29 Jun 2012 09:10:00 +0200

In the 1990's, an isogenic family of yeast strains, the Saccharomyces cerevisiae CEN.PK strains, was developed by crossing different laboratory strains. Since then, this family and especially the CEN.PK113-7D strain, has become widely used in systems biology studies, as well as in metabolic and evolutionary engineering studies. Because of the relevance of S. cerevisiae CEN.PK113-7D as a model strain, a large group of academic and industrial researchers set out to perform a de novo sequencing, assembly and annotation of the genome of this strain. The group identified almost 3000 indels (insertion/deletions) compared to the reference genome of S. cerevisiae S288C. A number of genes relating to maltose metabolism and biotin biosynthesis were identified in CEN.PK133-7D that is absent in S288C. It appears that CEN.PK133-7D is not only related to laboratory strains, such as S288C, but also to industrial strains. This may explain the robust physiological performance of CEN.PK113-7D in industrial settings. The annotated genome of S. cerevisiae CEN.PK113-7D is available through http://cenpk.tudelft.nl Nijkamp JF, van den Broek M, Datema E, de Kok S, Bosman L, Luttik MA, Daran-Lapujade P, Vongsangnak W, Nielsen J, Heijne WH, Klaassen P, Paddon CJ, Platt D, Kotter P, van Ham RC, Reinders MJ, Pronk JT, Ridder DD, Daran JM
De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology.
Microb Cell Fact 2012, 11:36, doi:10.1186/1475-2859-11-36

Get your data out there

Thu, 28 Jun 2012 16:13:00 +0200

The strong growth in sequencing capacity and application in a clinical setting is often heralded as an important step towards better diagnosis and better care. This is true only if we find a way to ensure that researchers and physicians around the world have easy access to data on gene variants generated by clinical laboratories, argues a group of researchers, including NBIC Faculty member Johan den Dunnen, in a commentary in The Clinical Biochemist Reviews. They offer a concise overview of why holders of gene variant information should submit their data to public database and what information is required. Plazzer J-P, den Dunnen JT, Smith T, Macrae F and Cotton RG
Reporting of genetic variants by diagnostic laboratories and other centres
Clin. Biochem. Rev. 2012, Vol 33(1):21-24

Polar interactions drive drug absorption

Tue, 26 Jun 2012 17:19:00 +0200

Being able to predict the absorption of drugs is highly relevant to drug discovery and drug development. In this respect, the concept of the polar surface area (PSA) has been successful. The PSA is defined as the combined surface area of oxygen and nitrogen atoms and the hydrogen atoms bound to these. To contribute to improving the correlation between PSA and absorbed drug fraction, Gijs Schaftenaar and Jacob de Vlieg (CMBI, Nijmegen) approached the problem from a quantum mechanical perspective. They focused on the role of the quantum mechanical electrostatic potential in drug absorption and were able to establish a correlation between the absorbed fraction and the so-called Quantum Mechanical Polar Surface Area (QMPSA) for structures where the carboxyl groups are deprotonated. Calculations on neutral gas phase optimized structures resulted in a much weaker correlation. According to the authors, this suggests that the polar interactions of the drug molecules in solution strongly determine the absorption process. Schaftenaar G and de Vlieg J
Quantum Mechanical Polar Surface Area
J. Comput. Aided Mol. Des. 2012, 26(3):311-318, doi:10.1007/s10822-012-9557-y

Plasmid-free LAB

Mon, 25 Jun 2012 15:31:00 +0200

Lactobacillus plantarum is one of the most versatile species of lactic acid bacteria (LAB), which are widely used in food fermentation processes, but also inhabit the gastrointestinal tract. So far, four L. plantarum genomes have been sequenced. A group of Norwegian and Dutch researchers, including NBIC Faculty member Sacha van Hijum and Roland Siezen, has added the genome of a fifth strain, L. plantarum NC8 (CCUG 61730). A remarkable feature of this strain is that it is naturally plasmid free, which distinguishes it from other L. plantarum strains. NC8 has been used as a model strain in the development of genetic tools, as well as in general fermentation and metabolic engineering studies. Axelsson L, Rud I, Naterstad K, Blom H, Renckens B, Boekhorst J, Kleerebezem M, van Hijum S and Siezen RJ
Genome Sequence of the Naturally Plasmid-Free Lactobacillus plantarum Strain NC8 (CCUG 61730)
J. Bacteriol. 2012, Vol.194(9):2391-2392, doi:10.1128/JB.00141-12

Where the genome breaks

Mon, 25 Jun 2012 15:24:00 +0200

Human genetic variation is not only caused by mutations that alter the sequence. Structural variation, in which regions of the genome are for example duplicated or deleted, is also an important source of genetic diversity between individuals. One, by now well-known form of structural variation is the so-called copy-number variation (CNV). Here, the variation does not relate to the sequence of a particular gene, but lies in the number of copies present. One of the reasons for CNV to gain a lot of attention lately is that de novo CNVs have been linked to a number of disorders and diseases. To learn more about the fundamental mechanisms that underlie genome plasticity and genomic rearrangement processes, it is essential to determine the exact breakpoints within the genomic regions that are duplicated. Such repetitive regions, segmental duplications, are characterized by high sequence identity, which makes it very difficult to precisely localize the breakpoints. Furthermore, gaps in the human genome reference often occur precisely at the expected breakpoints. By combining somatic cell hybrids, array comparative genomic hybridization and next-generation sequencing, Andy Itsara (University of Washington) and colleagues (including NBIC faculty member Edwin Cuppen of the Hubrecht Institute) managed to determine CNV breakpoints with molecular resolution in three individuals diagnosed with the 17q21.31 microdeletion syndrome. Itsara A, Vissers LELM, Meltz Steinberg K, Meyer KJ, Zody MC, Koolen DA, de Ligt J, Cuppen E, Baker C, Lee C, Graves TA, Wilson RK, Jenkins RB, Veltman JA and Eichler EE
Resolving the Breakpoints of the 17q21.31 Microdeletion Syndrome with Next-Generation Sequencing
Am. J. Hum. Gen 2012, Vol 90(4):599-613

A warm winter with NBICs advanced NGS courses - presenting our LS course overview for 2012

Mon, 25 Jun 2012 15:10:00 +0200

In recent years NBIC has set up the successful PhD school for bioinformaticians and is now filling the Life Sciences (LS) programme. Following up on the “Next Generation Sequencing (NGS) data analysis” course co-organized with LUMC, NBIC presents a set of four advanced NGS courses to offer a solid foundation to Life Sciences researchers in this field. All NBIC NGS courses are co-developed and co-organised by experts in the field and in close collaboration with leading research groups throughout the Netherlands. The first two courses had a first run in the past year and were well received or as one of the participants of the Genomics Resequencing course stated: “I would certainly recommend this course to anybody that deals with NGS…”. All courses are open for national and international participants from both public and private parties. NBIC NGS Course overview (2012-2013):

Next Generation Sequencing (NGS) data analysis, 6th edition (September 11-13th, 2012, Rotterdam).
Advanced NGS course: RNA-seq data analysis (2nd edition, October 2012). See also the programme of the first edition of this course.
Advanced NGS course: Metagenomics approaches and data analysis (November 2012)
Advanced NGS course: de novo assembly from NGS data (end of 2012)
Advanced NGS course: Genomic resequencing - Variant detection and interpretation in a diagnostic context (2nd edition, early 2013). See also the programme of the first edition of this course.

As soon as course dates have been set or when course programmes are available, these will be published on the NBIC website and on-line registration forms will be made available. As you can see, NBIC is expanding its activities and domains. We are open for your ideas about new topics and additional courses you would like us to organise or you would like to organise with us. For more information about the BioWise LS programme, please look at www.nbic.nl/education/biowise or send an e-mail to Patrick Koks or Celia van Gelder at education@nbic.nl.

Workshop on cross technology

Thu, 21 Jun 2012 11:27:00 +0200

Friday June 1st, the Dutch Tech Centre for Life Sciences (DTL) organized a workshop with representatives from key Life Sciences technologies: sequencing, proteomics, metabolomics, bioimaging, data integration and stewardship (bioinformatics, systems biology and e-science). It was a real WORK shop where the invited participants discussed what infrastructure, expertise, organisation and funding are required to successfully run cross technology projects. The discussions were centred on case studies, such as an integrated biology approach for cancer treatment and an enabling technology platform for plants. The case studies and the “slow-dating” lunch offered ample opportunities for “cross-technology encounters”. That way, the workshop was also a first event to meet each other and build on the DTL community. If you also want participate in DTL, you can visit the DTL website, join the group on LinkedIn or follow DTL on Twitter (#DTL_nl). A photo impression of the workshop is available on de DTL website.

Genalice has won ICT Innovation Award

Thu, 07 Jun 2012 13:41:00 +0200

Genalice, partner in the NBIC consortium, has won the ICT Office Innovation Award for its Biomarker Discovery Platform for Oncology. Summary of the jury report: “Genalice has shown that a small company in collaboration with other private parties, academia and medical centres can develop smart solutions. The BioMarker Discovery Platform will help the medical science to do faster and cheaper analyses in order to provide tailor-made treatment for cancer patients.” You can read the full Press Release (in Dutch) on the website of Genalice.

GRASS, a novel assembly scaffolder

Thu, 07 Jun 2012 11:26:00 +0200

Sequencing a genome may have become a routine activity, it still remains a serious puzzle to put the millions of small DNA fragments or short reads, back together to form the complete genome. The first step is assembling the short reads into longer sequences, the contigs. Using additional information, such as reference sequences of related organisms, the contigs are then put in the right order with the right orientation and at the right distance in even longer sequences called scaffolds.

In this scaffolding process, researchers are confronted with the Contig Scaffolding Problem (CSP), which simply is about finding the best ordering and orientation of the contigs without violating (too many of) the constraints related to contig order, orientation and distance that are derived from existing data. Several scaffolding algorithms are available, each with their own approach to addressing the CSP. Alexey Gritsenko and colleagues from Delft University of Technology add a new scaffolding algorithm to the repertoire. GRASS (GeneRic ASsembly Scaffolder) tackles the CSP by combining the contig order, distance and orientation in a single optimization objective. Compared to SSPACE, OPERA and MIP, three established scaffolding algorithms, GRASS generated comparable or lower number of scaffolds with higher accuracy.

GRASS source code is freely available: http://code.google.com/p/tud-scaffolding

Gritsenko AA, Nijkamp JF, Reinders MJT and de Ridder D
GRASS: a generic algorithm for scaffolding next-generation sequencing assemblies
Bioinformatics 2012, 28(11):1429-1437, doi:10.1093/bioinformatics/bts175

Visit DTL online

Fri, 01 Jun 2012 15:40:00 +0200

The Dutch Tech Centre for Life Sciences (DTL) is a collaborative public-private initiative to provide high-end and pioneer technology to enable ground-breaking research in molecular biosciences. In essence, DTL is a strongly intertwined network of expert centres among the Dutch universities, university medical hospitals as well as public and private research institutes. NBIC is one of these expert centres and founding partner of DTL. To support the development and branding of DTL, the Community and Outreach Team developed a logo and website for DTL. In addition, a LinkedIn group is opened for discussions. Please join!

Course Announcement: Systems and Network approaches in Human Life Sciences

Thu, 24 May 2012 09:28:00 +0200

On June 11 & 12, 2012, the Amsterdam Institute for Molecules, Medicines and Systems (AIMMS) organizes a post-graduate course at VU University about Systems and Network approaches in Human Life Sciences. The course includes two key notes:

Ursula Klingmueller (German Cancer research Institute)
Matthias Heinemann (Molecular Systems Biology, RU Groningen)

One of the course organizers is NBIC Faculty Bas Teusink. More information can be found in the flyer attached, and the NBIC online course overview.

Many small improvements

Tue, 22 May 2012 16:38:00 +0200

First described in 1993, Nicolaides-Baraitser syndrome (NBS) is rare, severe disorder that causes a variety of symptoms. Most notable characteristics of NBS are sparse hair, typical facial morphology, distal-limb anomalies and intellectual disability. The lack of known familial cases of NBS suggests that the disorder is caused by de novo mutations. Employing exome sequencing in ten individuals with NBS and extended molecular screening in a larger group, Jeroen van Houdt (Catholic University Leuven) and a large group of colleagues from various institutes identified mutations in SMARCA2 as a cause of NBS. SMARCA2 is a member of the family of Snf2 helicase proteins. A nice study, according to Antoine van Kampen who, together with shared first author Barbera van Schaik (Academic Medical Centre, Amsterdam), performed the bioinformatics analysis. "For us, this was the first exome sequencing study. We identified SMARCA2 to be linked to NBS and we were able to start functional studies into this protein."

Genome of the Netherlands
The ever-increasing amount of sequencing data proved helpful, says van Kampen. "In one of the validation steps, we compared our data to those of more than 200 genomes sequenced as part of the Genome of the Netherlands-project. In contrast to the NBS exomes with common SMARCA2 mutations clustered in the ATPase region we found no mutations in this region in the genomes, which supports our findings about the role of SMARCA2 in causing NBS." Although this study did not result in radically new insights from a bioinformatics perspective, projects like these are worthwhile, Van Kampen feels. "Here, the biological question and the biological data are in the lead. We implement and apply a bioinformatics analysis pipeline, which to a large extent is similar to the pipelines used by other groups. Nevertheless, every exome study allows us to further extent and refine the methods used in our pipeline."

Filters
Crucial to accuracy and usability of the analysis results are the filter steps. Starting with filtering out low-quality sequencing data, every step in the pipeline comes down to choosing which data to remove. Van Kampen: "We try to generate a manageable, high quality dataset for the biologists to process further. For bioinformaticians, the challenge is to choose the best filters for each particular question and dataset. What you find depends on how you search. We deliver suggestions for candidate-genes, which the biologists try to validate. Depending on discussions with the biologists and/or the outcome of the validation, we have to adjust the filters and go through the data again. It sometime happens that your filters remove the crucial data."

Imperfections and unknowns
With the outcomes being so dependent on the selection method applied, how reliable is the information generated by such an analysis? Van Kampen: "The bioinformatics workflow is certainly not perfect yet. Chances are that when you apply a different workflow to the same dataset, you come up with different or partially different results. Studies that compare the effect of different components of the workflows could potentially help in identifying the best way to set up an analysis pipeline. However, such studies are scarce." He mentions the lack of a golden standard. "That is a major problem. Work in that direction is ongoing, but we are not there yet." Imperfections in bioinformatics are however not the only problem as sequencing data are also not perfect. Van Kampen: "We are dealing with many unknowns. You're looking for an unknown gene using experimental and analysis methods that are both still subject to continuous development."

Van Houdt JKJ, Nowakowska BA, Sousa SB, van Schaik BDC, et al.
Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome
Nature Genetics 44, 445-449 (2012); doi:10.1038/ng.1105

Take extracellular phosphate into account

Mon, 21 May 2012 14:53:00 +0200

In comparative systems biology, the dynamic interactions between components in biological systems are studied - both experimentally and through modelling - to gain insight into the differences and similarities in behaviour of related organisms. Jennifer Levering (University of Heidelberg), NBIC Faculty Bas Teusink (VU Amsterdam) and colleagues applied a comparative systems biology approach to the primary metabolism of two lactic-acid producing bacteria: Lactococcus lactis, a beneficial bacterium widely used in the dairy industry and Streptococcus pyogenes, a human pathogen. In spite of the many differences between their natural environments, both bacteria exhibit striking similarities in their central metabolism. Starting out by improving the kinetic model of L. lactis glycolysis, Levering et al. used those results to construct the first kinetic model of glycolysis in S. pyogenes. Both models point to an important regulatory role for extracellular phosphate, which is generally not included as an independent species in metabolic models. According to the authors, metabolic analyses should in the future pay more attention to the role of extracellular phosphate.

Levering J, Musters MWJM, Bekker M, Bellomo D, Fiedler T, de Vos WM, Hugenholtz J, Kreikemeyer B, Kummer U and Teusink B.
Role of phosphate in central metabolism of two lactic acid bacteria – a comparative systems biology approach
FEBS Journal, 279:1274-1290. doi:10.1111/j.1742-4658.2012.08523.x

Lodewyk Wessels appointed as professor

Tue, 15 May 2012 14:55:00 +0200

NBIC Faculty member Lodewyk Wessels has been appointed as professor at the Delft University of Technology where he will hold a chair in computational cancer biology. Lodewyk will fulfill this chair while remaining group leader of the Bioinformatics and Statistics group at the Netherlands Cancer Institute. The Netherlands Bioinformatics Centre congratulates Lodewyk with his new position!

What you need to know about licensing

Thu, 10 May 2012 10:19:00 +0200

On 25 May, NBIC and the Netherlands Metabolomics Centre host a workshop on 'Software licensing and valorisation'. Rob Hooft, chief technology officer at NBIC explains why licensing is an important topic for the bioinformatics community.

Too late
"NBIC aims for a broad usability of the software that is developed within the various projects. We think it is important to ensure that others can easily benefit from the tools and programs we develop here and that is why we support open source software", Hooft starts out. "The problem is that many software developers as well as their group leaders are unaware of what an open source license actually means and what the requirements and possibilities are." According to Hooft, too often people starting thinking too late about the use of their software by others. Will others be interested in their software? Under what terms do they want to share their software with others? Are these terms acceptable to potential users? Do the developers intend to commercialize their software in the future? "It is very important to think about these aspects early on in the process, because they determine the boundary conditions and restrictions the developer has to deal with. Each choice comes with certain consequences and in this workshop, we want to present those consequences to stimulate the participants to think about these matters. The longer you wait, the more difficult it becomes to make changes."

Real life issues
During the workshop, actual cases will be presented and discussed. Hooft emphasizes that participants are very welcome to contribute problems and choices they are currently facing or cases they have dealt with. "It would be nice if we could really help participants during the workshop to make the right choice. That is why we do not present theoretical cases, but real life issues and projects."

For more information and registration, check:
http://www.nbic.nl/about-nbic/events/registration-forms/ba-progrmtng-25052012/

Participants interested in contributing to the programme, please contact Rob Hooft at: rob.hooft@nbic.nl

New mutations, new database

Thu, 10 May 2012 10:12:00 +0200

The CHARGE syndrome is a rare genetic malformation disorder in which several organ systems, such as eye, ear and nose are affected. CHARGE is the leading cause of congenital deafblindness. The syndrome is caused by mutations in CHD7, a member of the CHD protein family that plays a role in transcription regulation. In a review in Human Mutation, Nicole Janssen, NBIC Faculty Swertz and colleagues from the University Medical Centre Groningen discuss all currently described CHD7 variants, including 183 new pathogenic mutations identified by the authors. They also present a dedicated, locus-specific database that lists all CHD7 variants. The database is accessible at: http://www.CHD7.org .

Janssen N, Bergman JE, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RM, van Ravenswaaij-Arts CM and Hoefsloot LH
Mutation update on the CHD7 gene involved in CHARGE syndrome
Hum Mut 2012, doi:10.1002/humu.22086

Open Call for Converging Sciences

Tue, 08 May 2012 11:03:00 +0200

The Netherlands eScience Center (NLeSC) is announcing a project call to promote and facilitate cross-fertilization between disparate disciplines by facilitating the transfer of proven technologies from one domain to solve “Big Data” challenges in other scientific domains. In this context, Big Data is defined as the scientific challenge of dealing with the increasing scale of data generation (volume), but also the equally complex challenges of dealing with the increasing speed of data generation (velocity) and the need to manage massively heterogeneous datasets (variety). NLeSC is a joint initiative of SURF and NWO and has been operational since July 2011. NLeSC has an annual budget of €6M and collaborates with scientific research groups from both academia and industry to conduct funded projects in the natural sciences, humanities and social sciences, balancing short-term eScience results and the development of a longer-term eScience strategy. The most important component of the NLeSC strategy revolves around the funding of collaborative research following a peer reviewed call procedure with the objective to change scientific practice by enabling large-scale “Big Data” analysis across multiple disciplines by:

optimizing scientific discovery in the era of “big-data”;
stimulating new ways to do science only possible using advanced computing;
challenging traditional research by creative & innovative use of eScience & other computer-based methods;
pioneering new techniques needed to explore & connect relevant (massive) datasets.

Successful project applications can be funded to a maximum of €500K and is open to researchers from any Dutch university or research institute which is affiliated with NWO or KNAW. Details of the open project call can be found at: http://www.esciencecenter.com/projects/project-calls/

Prize winners at NBIC 2012

Mon, 07 May 2012 16:46:00 +0200

Who is best at presenting their project and scientific results to a conference audience? According to the audience of the NBIC2012 conference Marlies v/d Wees gave the best poster presentation. Her poster collected the most “like stickers” of conference participants and therefore she received the NBIC Poster Award 2012. Patrick Deelen was awarded by the BioWise Student Poster Prize 2012 for the best BSc/MSc poster presentation, selected by a special poster committee. A jury of senior scientists selected Marnix Medema as winner of the Best Lecture Award for his presentation about “Computational Genomics and Synthetic Biology Implementation of Microbial Secondary Metabolite Biosynthesis Pathways”. And the Application Showcase was won by Kostas Karasavvas for showing his application to “Run Taverna workflows from the web”. Congratulations to all of you!

Ortho-Profile: Finding distant relatives

Thu, 26 Apr 2012 16:54:00 +0200

Predicting the function of proteins relies heavily on finding protein 'relatives' (orthologs) of known function in other organisms by comparing sequence data and other information. But when sequence similarity is lacking, for example due to large evolutionary distances or high rates of sequence evolution, potential orthologs could be overlooked. Radek Szklarczyk, Bas Wanschers (Radboud University Nijmegen Medical Centre) and colleagues introduce Ortho-Profile, an iterative prediction method that applies reciprocal best hits at three different levels to infer orthology. Next to sequence-to-sequence comparisons, this method also includes profile-to-sequence and profile-to-profile comparisons. The researchers applied Ortho-Profile in a large-scale prediction of human orthologs of mitochondrial proteins of two model species, the fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. The analysis resulted in an increase in ortholog detection by 20% compared to solely using sequence-to-sequence comparisons. Based on this analysis, the authors suggest 15 candidate proteins for inclusion in the human mitochondrial proteome.

Szklarczyk R, Wanschers BFJ, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MAM, Gloerich J, Lasonder E, van den Heuvel LP, Nijtmans LG and Huynen MA
Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase
Genome Biology 2012, 13:R12

Call for papers Interfacing bio- and medical informatics

Thu, 26 Apr 2012 16:47:00 +0200

From 24 to 26 September 2012 the International Federation for Information Processing (IFIP) is having its World Computer Congress WCC2012 in Amsterdam, the Netherlands (www.wcc-2012.org). During the WCC2010 conference in Brisbane, Australia, IFIP and the International Medical Informatics Association (IMIA) organized a joint conference for the first time in their history. Also this time a joint one-day associated meeting will be held on Thursday 27 September. The topic of this meeting will be the link between bioinformatics and medical informatics. IFIP’s Working Groups 5.13 Bioinformatics and its applications and IMIA’s Working Group on Informatics in Genomic Medicine (IGM) are working in this area and supporting this event. You can submit papers for this conference before May 15th. Marcel Reinders, scientific director of NBIC, is member of the programme committee. More information: http://www.ifip.org/bim2012/.

Review: R-spondin proteins

Thu, 26 Apr 2012 11:19:00 +0200

The canonical Wnt signalling pathway plays a central role in key biological processes like cellular proliferation, cell differentiation and stem cell maintenance. During embryonic development, Wnt signalling is involved in almost every crucial decision step. The four members of the relatively recently discovered R-spondin protein family act as agonists to the Wnt signalling pathway and are as such highly interesting study objects. However, also in their own right, R-spondins deserve attention as they control for example the sex phenotype (male or female) of an embryo and are crucial to the development of limbs, lungs and the placenta. In a review in Genome Biology, Wim de Lau, Berend Snel and Hans Clevers (Hubrecht Institute/University Medical Centre Utrecht) bring together current knowledge on the evolutionary history of R-spondins, structural features, roles in embryogenesis and operational mechanisms. The authors also present future opportunities and challenges in R-spondin research.

de Lau, WBM, Snel B, Clevers HC
The R-spondin protein family
Genome Biology 2012, 13:242

Splicing alternatives

Thu, 26 Apr 2012 11:10:00 +0200

Increasing protein diversity is one of the roles attributed to alternative splicing – the frequently occurring mechanism in which multiple transcript isoforms are produced from a single gene. Genome-wide studies in plants have shown that alternative splicing is responsible for increasing the transcriptome complexity, but it remains unclear whether this also results in function diversity on the protein level. That requires detailed analysis of the alternative splicing process relating to individual genes or gene families. Edouard Severing (Plant Research International/Wageningen University) and colleagues selected the well-studied MADS domain transcription factor family, for an in silico analysis of the potential impact of alternative splicing on protein-protein interactions of MADS domain proteins. Their results support the impact of alternative splicing on a subgroup of this family that followed earlier genome-wide studies. The authors state that their detailed approach has the power to reveal relevant alternative splicing events that are not distinguishable in global patterns.

Severing EI, van Dijk ADJ, Morabito G, Busscher-Lange J, Immink RGH and van Ham RCHJ
Predicting the impact of alternative splicing on plant MADS domain protein function
PLoS ONE 7(1):e30524. doi:10.1371/journal.pone.0030524

New tool: xQTL workbench

Thu, 19 Apr 2012 11:38:00 +0200

With xQTL workbench, analysing large and complex datasets using QTL (quantitative trait loci) methods becomes easier than before. xQTL workbench allows QTL mapping at multiple levels, visualization of QTL profiles, addition of new algorithms, exploring underlying information and scalable data management. Using Molgenis software, xQTL workbench can be customized according to individual needs and preferences. xQTL workbench runs on all common platforms and is available through www.xqtl.org. Arends D., van der Velde KJ, Prins P, Broman KW, Möller S, Jansen RC and Swertz MA
xQTL workbench: a scalable web environment for multi-level QTL analysis
Bioinformatics 2012, 28(7):1042-1044.

NBIC is first virtual organisation in SURFconext

Mon, 05 Mar 2012 13:16:00 +0100

NBIC is the first virtual organisation connected to SURFconext as identity provider. Before, only institutions could connect to the collaboration infrastructure. NBIC is the first distributed (“virtual”) organisation that can serve as identity provider. SURFconext is a next generation collaboration infrastructure that creates new opportunities to collaborate online based on a combination of applications from different providers. Researchers, educators and students wish to select the tools that best fit their online collaboration needs. Organizations struggle with the integration of self-hosted services with commercial cloud services and service providers seek for ways to make their services easily accessible for users in higher research and education. SURFconext offers interesting clues to facilitate these needs. See also the news (in Dutch) on the Surf-website. More information about SURFconext:
http://www.surfnet.nl/en/Thema/coin/Pages/default.aspx

EBI Bioinformatics Roadshows in Rotterdam

Mon, 27 Feb 2012 10:48:00 +0100

EBI offers the opportunity to invite EBI trainers for an EBI Roadshow. Every roadshow is a collaboration between the local host and EBI trainers, who will teach how to use databases relevant to the research at the location. This summer ErasmusMC /MolMed will host two EBI Bioinformatics Roadshows. EBI: Bioinformatics Roadshow I:

Day 1: Functional Genomics Erasmus MC, 08 May 2012
Day 2: ENA and Ensembl developments & data warehouse Erasmus MC, 09 May 2012
Day 3: Sequence Searching and Alignment Erasmus MC, 10 May 2012

EBI: Bioinformatics Roadshow II

Day 1: Proteomics Erasmus MC, 12 June 2012
Day 2: GO, Interactions and Pathways Erasmus MC, 13 June 2012

For more information take a look on the MolMed website.

Revealing deletions

Tue, 21 Feb 2012 13:07:00 +0100

NBIC Faculty Edwin Cuppen and colleagues performed multiplexed genomic enrichment and next-generation sequencing on deleted regions of patients suffering from mental retardation. Their approach is a targeted and highly sensitive method that can help in investigating missing heritability in genome-wide screening studies. Generally, it is believed that in sporadic patients suffering from mental retardation de novo deletions are pathogenic. However, in a similar inherited deletion the phenotypic effect of the genes present in the deleted region is compensated by the normal functioning genes supplied by the other healthy parent. Only when an inherited deletion happens to overlap with de novo or inherited damaging alleles on the other chromosome, the phenotypic effect of the genetic damage is revealed. This recessive mode of inheritance requires new diagnostic approaches as it may be overlooked by routine methods. To study whether this unmasking mechanism contributes to the phenotype of patients with mental retardation and/or multiple congenital abnormalities, Ron Hochstenbach, Martin Poot (both University Medical Centre Utrecht) and Isaac Nijman (Hubrecht Institute) and colleagues performed multiplexed genomic enrichment and next-generation sequencing on the deleted regions in the group of 20 patients. Although further functional validation is required to draw definite conclusions on the pathogenicity of the variants identified, the authors present their approach as a targeted and highly sensitive method that can help in investigating missing heritability in genome-wide screening studies.

Hochstenbach R, Poot M, Nijman IJ, Renkens I, Duran KJ, Van 't Slot R, van Binsbergen E, van der Zwaag B, Vogel MJ, Terhal PA, Ploos van Amstel HK, Kloosterman WP, Cuppen E
Discovery of variants unmasked by hemizygous deletions
Eur J Hum Genet. 2012

Life Sciences Pre-Seed Grant

Thu, 16 Feb 2012 13:21:00 +0100

The ninth round of the Life Sciences Pre-Seed Grant, is now open for submissions. All Life Sciences researchers thinking about starting up a company are invited to submit an application. Submission deadline: 20 March 2012, 15:00 hrs

And yet another complicating matter

Fri, 10 Feb 2012 10:11:00 +0100

As if trying to understand how gene expression is regulated isn't complicated enough, new levels of complexity keep on emerging. Such as the tissue-dependency of cis-regulation – the phenomenon that single nucleotide polymorphisms (SNPs) can affect the expression of genes that are located nearby on the genome. Recently is has become clear that the effect of such an 'expression-affecting SNP' or eSNP on gene expression levels differs between different tissues. To assess the mechanisms by which genetic variants mediate gene expression, Jingyuan Fu (University Medical Centre Groningen) and colleagues compared the cis-effect of SNPs on gene expression levels in blood, liver, muscle and fat tissue. They propose four molecular models of tissue-dependent cis-regulation, of which opposite allelic direction is the most striking. Even though this model is probably the least common, its impact is huge as in different tissues the effect on gene expression is completely opposite. The authors therefore emphasize the need to use expression data from disease-relevant tissue when studying complex traits.

Fu J, Wolfs MGM, Deelen P, Westra HJ, Fehrmann RSN, te Meerman GJ, Buurman WA, Rensen SSM, Groen HJM, Weersma RK, van den Berg LH, Veldink J, Ophoff RA, Snieder H, van Heel D, Jansen RC, Hofker MH, Wijmenga C, Franke L
Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression
PLoS Genet 8(1):e1002431. doi:10.1371/journal.pgen.1002431

FAME: Modeling made easy

Thu, 09 Feb 2012 10:40:00 +0100

To facilitate systems biologists in their efforts to build genome-scale metabolic models, Joost Boele, Brett Olivier and Bas Teusink (VU Amsterdam) offer FAME - the Flux Analysis and Modeling Environment. FAME is a one-stop-shop as it combines the three key points in modeling, being model creation, result generation and interpretation, all into one open source, web-based tool. FAME, as well as a manual and a quick-start tutorial, can be accessed at: http://f-a-m-e.org/

Boele J, Olivier BG, Teusink B
FAME - the Flux Analysis and Modeling Environment
BMC Systems Biology 2012, 6:8, doi:10.1186/1752-0509-6-8

Alternative transporters

Thu, 02 Feb 2012 16:29:00 +0100

Microorganisms, especially those used in industrial production, are constantly under pressure to perform better. Generating microorganisms with improved characteristics is either done through direct engineering, which requires knowledge of the underlying genetic determinants, or through laboratory evolution, which opens the way for new mutations to occur in a more 'natural' process. Stefan de Kok (Delft University of Technology) and colleagues used laboratory evolution followed by transcriptome analysis and whole-genome resequencing to look for alternative lactate transporters in Saccharomyces cerevisiae (baker's yeast). So far, only one lactate transporter, Jen1p, has been documented in this yeast. The resequencing effort proved crucial and resulted in the discovery of single-nucleotide changes in ADY2, an acetate transporter gene. Introduction of these ADY2 alleles in a S. cerevisiae jen1∆ ady2∆ strain demonstrated that these alleles encode efficient lactate transporters.

de Kok S, Nijkamp JF, Oud B, Roque FC, de Ridder D, Daran JM, Pronk JT, van Maris AJ
Laboratory evolution of new lactate transporter genes in a jen1∆ mutant of Saccharomyces cerevisiae and their identification as ADY2 alleles by whole-genome resequencing and transcriptome analysis.
FEMS Yeast Research 2012 1-16. doi:10.1111/j.1567-1364.2012.00787.x

Cracking mitochondrial ribosome assembly

Thu, 02 Feb 2012 13:34:00 +0100

So far, already an extensive number of factors involved in the biogenesis of cytosolic ribosomes have been identified. However, when it comes to mitochondrial ribosomes, there is still a lot to be learned. For example on the proteins involved in the assembly process. In their search for novel human mitochondrial ribosome-associated proteins, Bas Wanschers (Radboud University Medical Centre Nijmegen) and colleagues performed a comparative genomics study leading to the identification of C7orf30 as the human homolog of the plant protein iojap. According to the authors, their data point to a role for C7orf30 in ribosomal large subunit function.

C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation.
Wanschers BF, Szklarczyk R, Pajak A, van den Brand MA, Gloerich J. Rodenburg RJ, Lightowlers RN, Nijtmans LG, Huynen MA
Nucleic Acids Research, 2012, 1-12. doi: 10.1093/nar/gkr1271

Towards interoperable bioscience data

Mon, 30 Jan 2012 13:55:00 +0100

Fifty researchers representing 37 research groups from all over the world plead in Nature Genetics to use the ISA standard in order create data interoperability. Chris Evelo, group leader BiGCaT Maastricht University and NBIC Faculty, is one of the authors.

Shared, annotated research data and methods offer new discovery opportunities and prevent unnecessary repetition of work. Although funding agencies, journals and community initiatives encourage good data stewardship and sharing through the use of community reporting standards, data sharing remains challenging.

To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. The Nature Genetics paper describes the prerequisites for data commoning and presents an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' (ISA) framework to support that vision.

Chris Evelo explains: “ISA introduces new ways of analysing the enormous amounts of bioscience data. For instance: the possibility to compare all diabetes studies which describe diet changes”.

Nature Genetics 44, 121–126 (2012) doi:10.1038/ng.1054
http://www.nature.com/ng/journal/v44/n2/full/ng.1054.html

Crossing borders

Mon, 23 Jan 2012 14:20:00 +0100

The action of genes is regulated through interactions with other genes. Understanding gene regulatory networks is therefore crucial to gain insight into the molecular mechanisms that underlie health and disease. Building such networks that involve thousands of genes and millions of interactions requires large-scale experimental datasets that in practice are affected by all kinds of artifacts. In particular when studying rare diseases of which the underlying biology is still largely unknown, the limited number of available samples further complicates the issue. In a recent paper in PLoS Computational Biology, Seyed Yahya Anvar (Leiden University Medical Centre) and colleagues hypothesize that biologically relevant relationships between genes are often conserved across species and that interspecies gene networks should be more meaningful from a biological perspective. Working from this hypothesis, they develop the Dandelion algorithm to construct and train intraspecies Bayesian networks. They demonstrate their approach on a dataset comprising both animal model and human data on OPMD, a rare muscular disorder.

Anvar SY, Tucker A, Vinciotti V, Venema A, van Ommen GJB, van der Maarel SM, Raz V, 't Hoen PAC
Interspecies translation of disease networks increases robustness and predictive accuracy
PLoS Comput Biol 7(11):e1002258

Driven by design

Mon, 23 Jan 2012 12:14:00 +0100

Functional genomics experiments are increasingly determined by a predefined experimental design. The design drives data generation and determines how the resulting data sets are organised. Knowledge of the underlying experimental design is therefore important to ensure adequate data analysis. Several methods have become available that utilize the underlying experimental design. Age Smilde (University of Amsterdam) and colleagues compared these methods and developed a general framework that supports researchers in understanding the differences between the methods, how to deal with factor effects that stem from the design used and selecting an alternative analysis method that might offer a better fit with their particular biological question.

Smilde AK, Timmerman ME, Hendriks MMWB, Jansen JJ, Hoefsloot HCJ
Generic framework for high-dimensional fixed-effects ANOVA
Briefings in Bioinformatics 2011, doi:10.1093/bib/bbr071

Resequencing: important, but hardly rewarded

Tue, 17 Jan 2012 08:50:00 +0100

With the advances in sequencing technology and analysis, the sequencing of genomes has become a routine activity. Even so, re-doing the whole exercise to improve your original sequence and annotation is much less common. The lactic acid bacterium Lactobacillus plantarum WCFS1 is one of the few organisms that have been 'honoured' with a complete resequencing and gene re-annotation.

Legacy
In 2001, a group of researchers from TI Food and Nutrition, Centre for Molecular and Biomolecular Informatics, NBIC and NIZO food published a sequence of L. plantarum WCFS1. Recently, they published the results of a complete resequencing and annotation efforts. Why go through all the motions again? "First of all, it is very important that a sequence and the annotation are as accurate as possible, because they are the starting materials for all subsequent research and analyses", says Sacha van Hijum, one of the contributors. "L. plantarum is one of the workhorses of the fermentation industry and it is a popular model system for research. There are so many researchers working with this bacterium that over the years an enormous amount of new knowledge and data on L. plantarum has been generated. But only the original authors of a sequence are allowed to make adjustments in the sequence and the annotation in the popular NCBI database. We wanted to do justice to this community effort and we also see the sequence and annotation as a legacy, which allows incorporating new insights and correcting inconsistencies."

Publication
Now that sequencing has become a lot faster and cheaper, does that mean we can expect a lot of re-sequencing efforts? Van Hijum: "Yes, I do think so, but it remains to be seen to what extent the results will be made public. I foresee that many labs will resequence the genomes of their 'own' strains, but will keep the results in-house. Unless you're an original author, it is very difficult to get this type of work accepted for publication. And that is a real shame because it is a common interest to update and improve sequencing information. With no 'reward' for this type of work, I think that many researchers will not bother to communicate their results to the broader community."

Siezen RJ, Francke C, Renckens B, Boekhorst J, Wels M, Kleerebezem M, van Hijum SAFT
Complete resequencing and reannotation of the Lactobacillus plantarum WCFS1 genome
Journal of Bacteriology 2012 (194:1), 195-196

Typing tuberculosis

Thu, 12 Jan 2012 15:01:00 +0100

Tuberculosis (TB) is one of the world's major health problems. It is estimated that roughly one-third of the global population is infected with Mycobacterium tuberculosis, the TB-causing pathogen. Especially for people with weakened immune systems (due to e.g. HIV infection, malnutrition or generally poor living conditions), TB is life-threatening. The so-called Beijing strains of M. tuberculosis have the dubious honour of being the most successful genotype of the pathogen, responsible for approximately 50% of the TB cases in Asia. The Beijing strains are also associated with the current multi-drug resistance TB epidemic in Eastern Europe and South Africa. To gain a more detailed understanding of the various strains within the Beijing genotype, Anita Schürch (National Institute for Public Health and the Environment, NL/Centre for Molecular and Biomolecular Informatics, Nijmegen, NL) and colleagues developed a typing scheme that uses SNPs and regions of difference (RDs) derived from whole-genome sequencing data of eight Beijing strains. Their analysis reveals that the Beijing strains' global spread was initiated on multiple occasions.

Schürch AC, Kremer K, Hendriks ACA, Freyee B, McEvoy CRE, van Crevel R, Boeree MJ, van Helden P, Warren RM, Siezen RJ, van Soolingen D
SNP/RD typing of Mycobacterium tuberculosis Beijing strains reveals local and worldwide disseminated clonal complexes
PLoS one, 2011, Vol 6, Issue 12

Variation OK, but not in name

Tue, 20 Dec 2011 14:12:00 +0100

The boost in sequencing efforts provides a wealth of information on genetic variants. This information is highly valuable to clinical diagnosis of disease, but requires unambiguous descriptions of the variants to prevent mistakes. A standard nomenclature for sequence variants has been established, but due to additions and extensions the complexity of this nomenclature makes it increasingly difficult for non-experts to understand and use. To assist clinicians and researchers, as well as database curators, Jeroen Laros and colleagues at the Leiden University Medical Centre have worked out formal descriptions of the syntax in Extended Backus-Naur Form (EBNF) on the DNA-RNA level and on the protein level. These descriptions can be easily modified and extended and can be used to develop new tools for text mining and other programmes used in the handling of sequence variant descriptions.

JFJ Laros, A Blavier, JT den Dunnen, PEM Taschner
A formalized description of the standard human variant nomenclature in Extended Backus-Naur Form
BMC Bioinformatics 2011, 12(Suppl 4):S5

Intriguing repeats

Mon, 19 Dec 2011 14:28:00 +0100

In protein sequences, amino acid tandem repeats are among the most prevalent patterns. There are several types of repeats. Repetitions of a single amino acid (single amino acid repeats, SAAR) such as polyglutamine (polyQ) and polyalanine (polyA) have been linked to neurodegenerative diseases. Other SAARs are thought to play a role in various biological processes, including network evolution (proline repeats) and protein localization (histidine repeats). Repeats with more complex patterns have also been extensively studied. For example, the role of leucine rich repeats (LRR) as the structural framework in protein-protein interactions.

So far, most of the research has been limited to studying the role of certain repeats within a single organism, but due to the lack of repositories for large-scale investigation and comparison of repeats from a variety of proteomes, drawing more general conclusions on the functional and evolutionary roles of repeats has not yet been possible. With ProRepeat, Hong Luo and colleagues from the group of Jack Leunissen (Wageningen University) aim to provide an integrated, curated and updated repository and analysis platform for the study of amino acid tandem repeats. ProRepeat is available through http://prorepeat.bioinformatics.nl
H Luo, K Lin, A David, H Nijveen, JAM Leunissen
ProRepeat: an integrated repository for studying amino acid tandem repeats in proteins
Nucleic Acids Research 2011

Correlated variation

Tue, 13 Dec 2011 09:17:00 +0100

In predicting functional sites in proteins, conservation of amino acids in sequence alignments is a well-known indicator of functional properties. In addition, correlated variation among amino acid positions tells something about which residues are located close to each other in the 3D structure can be applied for the prediction of intra- or intermolecular contacts. Current methods are limited to the analysis of pairwise correlations, but this obscures the difference between direct and indirect correlations. Observed correlation therefore thus not necessarily indicate that residues are located close to each other. In a paper in BMC Bioinformatics, Sreekumar et al. present a new method for Regularized Multinomial Regression to obtain Correlated Mutations (RMRCM) from protein multiple sequence alignments. Using simulated and biological datasets, good performance of the method was shown.

RMRCM is available in R-code via www.ab.wur.nl/rmrcm
J Sreekumar, CJF ter Braak, RCHJ van Ham, ADJ van Dijk
Correlated mutations via regularized multinomial regression
BMC Bioinformatics 2011, 12:444

OntoCAT: easy ontology search

Mon, 12 Dec 2011 13:04:00 +0100

In annotating life sciences data, ontologies are quickly gaining importance. Several ontology access resources are available, but these are not always easy to use and the differences in content and mode of operation makes integration with research data difficult. OntoCAT, developed by a team of bioinformaticians at the European Bioinformatics Institute and NBIC faculty member Morris Swertz (University of Groningen) offers a user-friendly interface to query heterogeneous ontology resources.

OntoCAT has been successfully applied in various use cases and is available through: www.ontocat.org
T Adamusiak, T Burdett, N Kurbatova, KJ van der Velde, N Abeygunawardena, D Antonakaki, M Kapushesky, H Parkinson, MA Swertz
OntoCAT - simple ontology search and integration in Java, R and REST/JavaScript
BMC Bioinformatics 2011, 12:218

N Kurbatova, T Adamusiak, P Kurnosov, MA Swertz, M Kapushesky
ontoCAT: an R package for ontology traversal and search
Bioinformatics 2011, 27:17

Conserved yet flexible

Tue, 29 Nov 2011 11:58:00 +0100

In eukaryotic growth, a major regulatory role is played by the protein TOR (target of rapamycin). TOR is a kinase - a protein that phosphorylates other proteins - and is part of two protein complexes called TORC1 and TORC2. Both complexes are components of important pathways: TORC1 is activated by the insulin signalling pathway and TORC2 regulates cytoskeleton rearrangement in response to growth. Dysfunction of TOR or other components in TOR pathways is linked to cancer development. Although TOR has been characterised in animals, fungi and plants, not all of the TOR complex subunits or pathway components have been equally conserved. To study the evolution of the TOR pathway, John van Dam and colleagues at Utrecht University, performed phylogenetic analyses on the components of the TOR pathway. They found that TOR, the subunits of the two TOR complexes and a large part of the pathway components form an evolutionary core, while other regulatory inputs have been added to the pathway during evolution. According to van Dam et al., their results show that a highly conserved pathway can also be flexible. TJP van Dam, FJT Zwartkruis, JL Bos, B Snel
Evolution of the TOR pathway
Journal of Molecular Evolution, published online 5 November 2011 By: Esther Thole

Improving cancer gene identification

Tue, 29 Nov 2011 11:51:00 +0100

Actively causing mutations to disrupt cellular processes and thus, perhaps, cause cancer in mouse models is a widely used approach to find cancer genes and study affected regions in the genome. This process, called insertional mutagenesis, employs retroviruses and transposons that are integrated into the host DNA. Identifying which genes are affected by these insertions and are responsible for cancer development is not yet a straightforward task. To improve the analysis of large-scale insertional mutagenesis screens, Johann de Jong (Netherlands Cancer Institute) and colleagues developed Kernel Convolved Rule Based Mapping (KC-RBM), a computational method to map integration sites to target genes. When compared to existing methods, KC-RBM showed superior performance in identifying true positives. KC-RBM is available as R-package. J de Jong, J de Ridder, L van der Weyden, N Sun, M van Uitert, A Berns, M van Lohuizen, J Jonkers, DJ Adams, LFA Wessels
Computational identification of insertional mutagenesis targets for cancer gene discovery
Nucleic Acids Research 2011, (39), 15 published online 7 June 2011 By: Esther Thole

Information system for nuclear hormone receptors

Fri, 25 Nov 2011 15:56:00 +0100

This month, Bas Vroling (CMBI Nijmegen) published the NucleaRDB. NucleaRDB is a Molecular Class-Specific Information System that collects, combines, validates and disseminates large amounts of heterogeneous data on nuclear hormone receptors. It contains both experimental and computationally derived data.

The data and knowledge present in the NucleaRDB can be accessed using a number of different interactive and programmatic methods and query systems. A nuclear hormone receptor-specific PDF reader interface is available that can integrate the contents of the NucleaRDB with full-text scientific articles. NucleaRDB is freely available at http://www.receptors.org/nucleardb.

NucleaRDB: information system for nuclear receptors.
Vroling B, Thorne D, McDermott P, Joosten HJ, Attwood TK, Pettifer S, Vriend G.
Nucleic Acids Res. 2011 Nov 7

WikiPathways: new features for a growing community

Fri, 25 Nov 2011 15:11:00 +0100

New features of WikiPathways, a public wiki for pathway curation, are discussed in the November issue of Nucleic Acids Research. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein.

WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and since it was first published in 2008 the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further.

http://www.wikipathways.org
WikiPathways: building research communities on biological pathways.
Kelder T, van Iersel MP, Hanspers K, Kutmon M, Conklin BR, Evelo CT, Pico AR
Nucleic Acids Res. 2011 Nov 16

Dutch Techcentre for Life sciences (DTL)

Fri, 18 Nov 2011 11:24:00 +0100

November 22^nd, at Life Sciences Momentum, six top expertise centres together presented the Dutch Techcentre for Life sciences (DTL). DTL is their answer to the rapidly growing need for high-end technologies in biomedical and biotechnological research. Mission of DTL is to give Dutch investigators in academia and industry access to up-to-date and high level expertise and equipment in the fields of next generation sequencing, proteomics, metabolomics, microscopy and data integration and stewardship.

DTL builds on centres of excellence, several of which have been established under the umbrella of the Netherlands Genomics Initiative (NGI). These are:

•   Netherlands Bioinformatics Centre (NBIC), www.nbic.nl
•   Netherlands Consortium of Systems Biology, (NCSB), www.ncsb.nl
•   Netherlands Metabolomics Centre (NMC), www.metabolomicscentre.nl
•   Netherlands Proteomics Centre (NPC), www.netherlandsproteomicscentre.nl
•   Centre for Genome Diagnostics (CGD)
•   Netherlands Society for Advanced Light Microscopy

Ruben Kok, managing director of the Netherlands Bioinformatics Centre (NBIC), explains: “No single research group, institute, university, or company will be able to maintain all key big life science technologies at a sufficiently high level. To secure the frontline position of Dutch R&D a new approach is needed to make these technologies available in a more efficient and cost-effective way. DTL offers dedicated technology expertise and collaborative research facilities that are coordinated at the national and international level.”

A growing urgency to change

Thu, 17 Nov 2011 09:53:00 +0100

According to Johan den Dunnen there are no valid reasons for not publishing all data on gene variants in a public database. "We urgently need access to this information, otherwise it is useless to perform whole genome analysis."

For a long time already, multiple efforts are ongoing to make all discovered gene variants accessible through public databases. So far, progress has been very limited and there is still no easily accessible, internationally accepted database that brings all the information (gene variants, phenotype descriptions, clinical information) together. "Currently, the vast majority of gene variants are not published at all. Academic and commercial diagnostic labs, as well as most researchers don't bother to make their findings available to the community", says den Dunnen, professor of Medical Genome Technology at the Leiden University Medical Centre. Discussions on the need for a standardized, curated and publicly accessible database have been going on for a long time, but the advent of whole genome sequencing in routine clinical practice is creating a sense of urgency. Den Dunnen: "The extent of the problem is dawning quickly. You can deal with three variants in the conventional manner of analysis, but confronted with a list of 10,000 variants or more, you are nowhere if you don't have access to a central resource for retrieval of relevant information. Using modern sequencing technology, clinical geneticists and diagnostic labs are confronted with such lists. The urgency is high and will only increase because physicians and patients will want the results on short notice."

MutaDATABASE
One of the initiatives that aim to come to a manageable and sustainable solution is MutaDATABASE (www.mutadatabase.org), in which den Dunnen is a participant. A correspondence by the MutaDATABASE consortium in Nature Biotechnology earlier this year (Feb 2011) led to a discussion with other initiatives in the field, including the Human Variome project and the Gen2Phen consortium. Den Dunnen emphasizes that he also participates in those initiatives and remains neutral on the back-and-forth comments that have been published in Nature Biotechnology (links listed below). "I am basically part of both sides in this discussion. This type of quarrelling usually comes up when an opportunity for funding is appearing. To me, the most important thing is that we are going to act. These discussions have been going on far too long already. We could have prevented this whole situation if we would have started acting ten years ago. It was clear that the technology was developing in this direction."

Compulsory
What is the crucial factor for this to become a success? How can you ensure that researchers will submit their data? Den Dunnen: "After many years I see only one solution, which is that it should be compulsory for anyone who performs such an analysis to submit the result and the accompanying clinical information in a public database and it should be obligatory to consult this database to interpret your results and formulate conclusions for the patient and physician." He does not share the much-heard concerns on privacy issues relating to such sensitive information. "Physicians are bound to act in the best interest of their patients and to me it is clear that having access to this information and thus sharing information is in the best interest of the patient. When nobody shares we can stop using DNA diagnostics because we have nothing to refer to. Many researchers and physicians use the need to be careful as an excuse, but this is really stalling the process. With the right software, all these concerns can easily be addressed." He has been around long enough that it will take a lot of time and effort to establish a new routine. But he stresses that there is no alternative. "If we don't make this work, the progress in sequencing technology has been in vain. Performing whole genome analysis is useless without access to this type of information. On the upside, if we have the funds and the will to change, we can make it happen in less than a year."

For the discussion in Nature Biotechnology, check

Bale et al.
MutaDATABASE: a centralized and standardized DNA variation database
Nature Biotechnology 29 117-118 (2011) (original correspondence)

Dalgleish et al.
Clarity and claims in variation/mutation databasing
Nature Biotechnology 29 790-792 (2011) (comment)

Bale et al.,
Reply to clarity and claims in variation/mutation databasing
Nature Biotechnology 29 792-794 (2011) (reply)

For related correspondence by members of the International Scientific Advisory Committee of the Human Variome Project (including Johan den Dunnen)
Mutation (variation) databases and registries: a rationale for coordination of efforts
Nature Reviews Genetics, doi:10.1038/nrg3011-c1 (published online 25 October 2011)

Pathway databases differ considerably

Thu, 17 Nov 2011 09:29:00 +0100

Studying and mapping the human metabolic network is an essential element in improving our understanding of human health and disease. A number of high-quality databases that contain data on human metabolic pathways have been constructed and have become an important and routinely used tool in biomedical research. Each database however contains part of the puzzle and the overall field would greatly benefit from an integration of all available data. To aid such integration, Miranda Stobbe (Academic Medical Centre, Amsterdam) and colleagues have performed the first, systematic comparison of five frequently used human metabolic pathway databases: BiGG, EHMN, HumanCyc, KEGG and Reactome. Their results show the overlap between the databases to be surprisingly low.

Stobbe MD, Houten SM, Jansen GA, Van Kampen AHC, Moerland PD
Critical assessment of human metabolic pathways: a stepping-stone for future integration
BMC Systems Biology 2011, 5:165

Genome of the Netherlands ready for the next level

Thu, 10 Nov 2011 10:27:00 +0100

The BBMRI-NL Rainbow Project Genome of the Netherlands project (GoNL) is ready for the next level. It has completed the alignment of all the DNA reads of the 750 individuals, producing a total of 350 billion reads. Based on these data, further analyses can be performed, enabling the development of new treatments and diagnostic techniques.

The GoNL project offers unique opportunities for science as it gives a close-up look at the DNA of 750 Dutch people—250 trio’s of two parents and an adult child—plus a global genetic profile of large numbers of Dutch people. This information will disclose a wealth of new insights and possible applications. A reusable pipeline has been assembled based on best practices in the field. Processing 250 trios represents a major computational challenge and required the assistance from SARA, CIT, Target, NBIC and BigGrid. Using both the national Grid infrastructure and cluster resources at the participating institutes, the GoNL project has already produced more than 300 TB of data. With the GoNL project BBMRI-NL expects to increase knowledge about the genetic variation in the Netherlands and complement international resources like the 1000 Genomes and HapMap Projects. The Genome of the Netherlands is an open national consortium of the UMCG, LUMC, Erasmus MC, VUMC, Hubrecht, AMC, RUNMC and UMCU led by Professor Cisca Wijmenga (GoNL) and Paul de Bakker & Morris Swertz (eBiobank). The sequencing work is done by BGI Hong Kong. More information about the project can be found on http://www.nlgenome.nl/ (GoNL) and http://www.bbmriwiki.nl/ (Bioinformatics) On our website you can find more information about the involved BioBanking Task Force and Genomics Task Force of NBIC.

All cells are not equal

Thu, 10 Nov 2011 10:17:00 +0100

Transcriptomics, i.e. studying gene expression levels in an organism, has become a routine activity in molecular biology. RNA is isolated from millions of cells and analysed using standard microarray technology. The resulting gene expression levels represent an average calculated from all those cells, which is very suitable to compare different individuals or populations, but obscures differences between individual cells.

However, it is also known that cellular heterogeneity is a widespread phenomenon. To gain insight into the extent of this heterogeneity in the filamentous fungus Aspergillus niger (a workhorse of the fermentation industry), Charissa de Bekker and Han Wösten (Utrecht University) performed the first-ever single cell transcriptomics measurements on microbial cells. They isolated RNA from five individual hyphae (the 'arms' of the fungus) of an A. niger colony, but their standard analysis methods were insufficient to deal with these absolute tiny amounts of material. "We basically did not have enough material to ensure proper hybridisation. Furthermore, as we were interested in individual cells, we had five unique datasets to deal with, without the duplicates you normally include. Clearly, we needed help", Wösten explains.

Through the Kluyver Centre, he became aware of the support offered by NBIC and contacted the group of Timo Breit (University of Amsterdam). "They really helped us out by applying advanced statistics to our datasets, so that we could generate reliable results. Without their contribution, we would never have been able to analyse the data." This would have been a shame, as their findings pave the way to a whole new area to be explored. Wösten: "We have shown that the general assumption that cells in a microbe are simply copies of each other is not true. Each cell is unique." Charissa de Bekker, Oskar Bruning, Martijs J Jonker, Timo M Breit and Han AB Wösten
Single cell transcriptomics of neighbouring hyphae of Aspergillus niger
Genome Biology 2011, 12:R71

Bioinformatics Research Support Team

Call for GRID papers

Tue, 08 Nov 2011 15:14:00 +0100

The tenth HealthGrid 2012 Conference will take place at the Amsterdam Medical Centre (21-23 May) in conjunction with the 4th International Workshop on Science Gateways for Life Sciences (23-25 May), and with the participation of the European Grid Infrastructure. This joint event will be an excellent opportunity for speakers to introduce and share novel ideas for the integration of grid, cloud and other e-infrastructures into the fields of biology, bioinformatics, biomedicine and healthcare, focusing on fundamental and practical aspects of middleware, technologies, applications and deployment issues. Calls for Papers are now open for both HealthGrid 2012 and IWSG-Life2012. The conferences welcome contributions covering topics that range from grid technologies through to biomedical research and from portals to workflow and computational modelling. Contributions should be submitted in the EasyChair system by January 16, 2012. All selected contributions will be published in PubMed-referenced proceedings in the IOS Press book series. More information:

Healthgrid 2012: http://amsterdam2012.healthgrid.org/
IWSG-Life 2012: http://iwsg-life.org/site/iwsglife2012/home
EGI: http://www.egi.eu

To the rescue!

Mon, 07 Nov 2011 10:59:00 +0100

Good news for those of you working on the family of G protein-coupled receptors (GPCR). Keeping up with the massive amount of literature and data has become a lot easier thanks to work by Bas Vroling (CMBI, Nijmegen) and colleagues. In a paper in BMC Bioinformatics, they describe the GPCR-specific PDF reader, a new tool that is now part of the GPCR database (GPCRDB, www.gpcr.org/7tm/). When using the tool to read a paper, annotated concepts are immediately visible, which provides the researchers with quick access to related publications and relevant data sources.

"Our main goal was to develop a reader that allows researchers to easily review, find and analyse data and relevant literature. When a user opens a paper, the system immediately provides feedback by highlighting the annotated concepts, such as proteins, residues and mutations. Importantly, this information is also stored by the system to keep the information flow up to date", Vroling explains. According to him, what makes their tool stand out from other tools that target the same problems is that they can validate their tools using the GPCRDB. "This validation step makes our work unique. It is essential to have access to a reliable data source. That is what we hope to show with our work as well. Developing text mining tools is only worthwhile when you can check your results against a well-maintained, curated database."

A particularly sympathetic feature of GPCR-specific PDF reader is that it can help to rescue old data from oblivion. Vroling: "Because past interpretations have turned out to be wrong, the raw data can still be very useful. Our tool can track this data down so it can be interpreted again using current insights."

Bas Vroling, David Thorne, Philip McDermott, Teresa K Attwood, Gert Vriend and Steve Pettifer
Integrating GPCR-specific information with full text articles
BMC Bioinformatics 2011 12:362

Your personal guide to modelling

Thu, 03 Nov 2011 16:36:00 +0100

When asked to contribute a paper on genome-scale metabolic reconstruction and models to Methods in Enzymology, authors Filipe Santos, Joost Boele and Bas Teusink (VU University Amsterdam) decided to take their personal experiences in this field as the guideline. "We all have hands-on experience in making these models and we all have faced similar obstacles and bottlenecks along the way", says Santos. With their 'practical guide', Santos and colleagues aim to help others who are starting out in this field or who want to refine their own efforts. He admits: "It is actually the kind of guide we would have liked to have had when we started out making our own models."

Filipe Santos, Joost Boele and Bas Teusink
A practical guide to genome-scale metabolic models and their analysis
Methods in Enzymology, Vol 500, 2011, pp. 509-532

Data fusion at high level

Wed, 02 Nov 2011 08:46:00 +0100

In the omics field, combining data from different sources – i.e. data fusion – is becoming more and more important. In so-called high-level data fusion, model predictions from two or more models are combined to produce a 'fused' response. High-level data fusion is amongst others applied in classification, but little is known about the possibilities for improving classification after data fusion. Timo Doeswijk (Wageningen University) and colleagues have analysed to potential increase in predictive performance of fusing two classifiers. They checked their models against a real data set generated by metabolomics studies on different types of tomato, which showed the applicability of their simulation results. T.G. Doeswijk, A.K. Smilde, J.A. Hageman, J.A. Westerhuis, F.A. van Eeuwijk
On the increase of predictive performance with high-level data fusion
Analytica Chimica Acta 705 (2011) 41-47

Competition for genomics data analysis tools

Tue, 01 Nov 2011 09:03:00 +0100

The "Complete Genomics Data Analysis Grant Program" organised by Complete Genomics will reward the development of innovative and unique tools for data analysis for use in analyzing Complete Genomics data sets. These tools would include data analysis software or scripts, methods, workflows or other resources used for downstream analysis of data with the MasterVar or Var file as the starting point. Eligible researchers should complete the program application, including an abstract, and submit this to Complete Genomics by midnight PST, on December 2, 2011.The application will be judged by a panel of Complete Genomics Commercial and Scientific leaders. The program timeline is as follows:

•   December 2: Deadline for application submission.
•   December 16: Judging completed, winner notified.
•   January 31, 2012: All samples must be received by Complete Genomics.

More information is available on their website that further describes
the program and associated Terms and Conditions:
http://www.completegenomics.com/news-events/grant-program/. Complete Genomics is a life sciences company that has developed and commercialized an innovative DNA sequencing platform for complete human genome sequencing and analysis.

A superficial analysis?

Tue, 25 Oct 2011 14:10:00 +0200

The interactions at the interface between the biomaterial used in a medical device, such as stents or implants, and surrounding tissue cells are crucial in determining the body's response to the device. To counter potential complications, the surface of the implant is treated with specific coatings or modified using physical techniques like 'sanding'. Although effective, these techniques provide little control of surface characteristics. Such control is offered by micro- and nanotechnologies. However, determining the distinct surface characteristics to elicit a wanted response remains a big challenge. In a PNAS publication, a group of tissue engineers and bioinformaticians, including NBIC-faculty member Marcel Reinders, describe how they constructed a library of more than 2,000 distinct, randomly designed surface topographies and how such libraries can help to unravel the still elusive interplay between cells and biomaterial surfaces.

Unadkat HV, Hulsman M, Cornelissen K, Papenburg BJ, Truckenmüller RK, Post GF, Uetz M, Reinders MJ, Stamatialis D, van Blitterswijk CA, de Boer J
"An algorithm-based topographical biomaterials library to instruct cell fate"
PNAS 2011 Oct 4; 108(40):16565-70

MADMAX: Advanced analysis, easy to use

Fri, 21 Oct 2011 09:19:00 +0200

The MADMAX database is specifically designed to store, manage and analyse data from a variety of ~omics sources. To demonstrate the features and powers of MADMAX, Ke Lin of Wageningen University and colleagues performed a pilot study using different types of ~omics data from Brassica rapa. Their findings were published in the Journal of Integrative Bioinformatics on July 21, 2011. A major feature of MADMAX is its ease of use; no programming is required to employ the system. The advanced analysis pipelines incorporated in MADMAX are based on R/Bioconductor and thus offer state-of-the-art analysis methods for multiple microarray platforms. MADMAX has already been widely used by scientists around the world. "The user-friendliness is a recurring element in the user feedback", says Anand Gavai, bioinformatician in the group of NBIC Faculty member Jack Leunissen at Wageningen University and co-author of the JIB paper. "Users particularly appreciate the fact that advanced analyses and statistics are supplied simply at the click of a button." More information on MADMAX: http://madmax2.bioinformatics.nl

MADMAX - Management and analysis database for multiple ~omics experiments
Lin K, Kools H, de Groot P, Gavai A, Basnet RK, Cheng F, Wu J, Wang X, Lommen A, Hooiveld GJ, Bonnema G, Visser RG, Muller MR, Leunissen JA Journal of Integrative Bioinformatics, 8(2):160, 2011

Overcoming bias in phosphoproteomics

Fri, 21 Oct 2011 09:07:00 +0200

Phosphorylation, i.e. adding a phosphate group to proteins, is a key step in numerous biological processes and pathways. Insight into the functional dynamics of phosphorylation networks is essential to understand how a living cell operates. Studying the phosphoproteome - all proteins involved in phosphorylation - has recently gained an enormous boost. But comparing and integrating data on phosphoproteomes is complicated due to incomplete datasets and to biases caused by the use of different experimental workflows. Jos Boekhorst (Utrecht University) and colleagues have developed bioinformatics strategies to quantify the impact of different experimental workflows on measured phosphoproteomes by comparing datasets to a common reference. Their strategies also offer possibilities for extracting information through comparative analysis of available phosphorylation data from sources not specifically generated for phosphoproteome studies. Evaluating experimental bias and incompleteness in comparative phosphoproteomics analysis
Boekhorst J, Boersema PJ, Tops BB, van Breukelen B, Heck AJ and Snel B PLoS One 2011;6(8):e23276

Snooker: a tool to predict medicine binding sites on GPCRs

Fri, 14 Oct 2011 14:20:00 +0200

G-protein coupled receptors (GPCRs) are important drug targets for various diseases and of major interest to pharmaceutical companies. Bioinformatics researchers developed Snooker, a tool to predict possible drug binding sites on these receptors.

Snooker: A Structure-Based Pharmacophore Generation Tool Applied to Class A GPCRs.
Sanders MP, Verhoeven S, de Graaf C, Roumen L, Vroling B, Nabuurs SB, de Vlieg J, Klomp JP J Chem Inf Model. 2011 Sep 26;51(9):2277-92

Van Beek models Lance Armstrong climbing Alpe d'Huez

Fri, 14 Oct 2011 13:45:00 +0200

The human physiological system is stressed to its limits during endurance sports competition events. Hans van Beek (VUMC) and other NBIC Faculty described a whole body computational model for energy conversion during bicycle racing. They simulated a mountain time trial to Alpe d'Huez during the Tour de France and calculated the energy and heat transfer needed to approach the time realized by Lance Armstrong in 2004. The model showed that the leg temperature can approach 40 degrees Celsius.

Read more:
http://www.vumc.nl/onderzoek/nieuws/6343633/

Website VUMC (in Dutch)
Simulating the physiology of athletes during endurance sports events: modelling human energy conversion and metabolism.
Philos Transact A Math Phys Eng Sci. 2011 Nov 13;369(1954):4295-315.
van Beek JH, Supandi F, Gavai AK, de Graaf AA, Binsl TW, Hettling H.

Gene duplication leads to tissue specificity

Fri, 14 Oct 2011 12:15:00 +0200

Gene duplication is one of the main mechanisms by which genomes can acquire novel functions. The group of NBIC Faculty Martijn Huynen studied the levels of tissue specificity after gene duplication, combining phylogenetic analyses and expression data from human and mouse. Their results show that gene duplication leads to increased levels of tissue specificity and that this tends to occur promptly after the duplication event. Evidence for short-time divergence and long-time conservation of tissue-specific expression after gene duplication.
Brief Bioinform. 2011 Sep;12(5):442-8 Huerta-Cepas J, Dopazo J, Huynen MA, Gabaldón T

Online demonstration of OpenPHACTS

Fri, 07 Oct 2011 16:43:00 +0200

The knowledge management project Open PHACTS (Open Pharmacological Concepts Triple Store) demonstrates the results of the first 6 months of the project in a You Tube video. It shows pharmacological queries over a number of datasets using multiple user interfaces.

About OpenPhacts
Open PHACTS (Open Pharmacological Concepts Triple Store) is a knowledge management project of the Innovative Medicines Initiative (IMI), a unique partnership between the European Community and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The Open PHACTS consortium is creating an open innovative platform, Open Pharmacological Space, which will be freely accessible for knowledge discovery and verification. NBIC researchers play a central role in the large-scale project, which focuses on data interoperability.

Vote for Leve DNA!

Wed, 05 Oct 2011 09:11:00 +0200

Leve DNA! is one of the finalists in the 'Academische jaarprijs'. They are in the running for winning an annual prize for the best public communication campaign of modern research. In short: the Leve DNA-plan wants to execute fun DNA-research that 'the public' can come up with. Together with high schools we will choose and elaborate twelve of such researches. We can, for example, compare the genome of the main Opera visitor with the genome of the main Lowlands-visitor. Or we can determine if chewing gum on the street near a hospital contains more pathogenic bacteria then the chewing gum near a high school. Hienke Sminia (NBIC) is part of the enthusiastic team (LUMC, LGTC, Naturalis and NBIC) and will help the team with the connection to high school education. But NBIC will of course also contribute in the bioinformatics support of these small scale researches. Part of the Academische jaarprijs is de public prize. This means that YOU can help us win! Vote for us via: http://www.wetenschap24.nl/programmas/labyrint/publieksprijs.html

NBIC Biobank Taskforce develops software for BBRMRI-NL Biobank Catalogue

Fri, 30 Sep 2011 13:38:00 +0200

In August, BBMRI-NL went online with its Biobank Catalogue. The NBIC Biobank Taskforce developed the software for the BBMRI-NL Biobank Catalogue. Based on the Molgenis framework developed in Groningen the Taskforce developed an online application where registered users can consult information on the 150+ Dutch biobanks associated with BBMRI-NL. All 150-plus Dutch biobanks currently associated with BBMRI-NL are in the catalogue, which is visible only for registered users and contains data on the type of tissue stored, GWAS- data, publications, etc. More information: http://www.bbmri.nl/nl-nl/biobanken-database

Subtyping makes sense

Tue, 13 Sep 2011 09:52:00 +0200

Predictive profiling, in which the gene expression profile of a tumour is used to predict for example the risk of metastasis (spreading of a tumour) in an individual cancer patient, is a hot topic among cancer researchers. Especially in breast cancer research, a lot of effort is dedicated towards developing reliable predictors for diagnosis and prognosis. A much-debated issue here is how to deal with the various subtypes of breast cancer. A novel protocol designed by PhD student Herman Sontrop and colleagues at Philips Research, Delft University of Technology and the Academic Medical Centre sheds a new light on this topic.

Unbalanced reference
"We now know that breast cancer is not one disease, but a collection of subtypes that show clear differences in terms of clinical outcomes, such as the risk of metastasis and survival rates. However, these differences are rarely taken into account in the development of predictors", says last author Perry Moerland, NBIC faculty member and assistant professor at the Academic Medical Centre, Amsterdam. This is due to two methodological drawbacks. Classification into subtypes reduces the sample size per subtype, which might impair the performance of a predictor. In addition, the complete non-subtyped dataset that is used as a reference is unbalanced with respect to the subtype distribution: the characteristics of the most prevalent subtype dominate the reference set, which impairs a realistic comparison for the less prevalent subtypes.

Strange behaviour
Convinced that using the characteristics of the breast cancer subtypes should lead to better predictors, Moerland and colleagues set out to find a way to circumvent the methodological obstacles. They took four breast cancer subtypes to work with: luminal A, luminal B, Her2 and basal, as these are generally accepted within the field. Moerland: "For each subtype, we built predictive models, as well as for all combinations of subtypes. Next, we compared the various models to see which performed best. An essential step was to come up with a good measure for the quality of our predictions. In many cases, the so-called balanced accuracy rate or bar is used in which both sensitivity and specificity are taken into account. However, when we combined the predictions of the four subtypes in one model, we noticed strange behaviour in the bar outcomes. It turned out that the bar of the combined model was higher than any of the individual bar scores of the subtypes."

Balancing the bar
Subsequent scrutiny of the bar itself revealed that the bar score is highly sensitive to the ratio between positive and negative outcomes. "And that ratio differs for each subtype. When combining all the subtyped models, this leads to a distorted overall score. In fact, the bar did not provide a true measure of the quality of the prediction", Moerland explains. They addressed this problem by constructing the models in two variants. In the balanced compendium, the volumes and ratios are controlled to prevent dominance of one single subtype and to control the ratio between positive and negative outcomes. This means leaving out data from the more prevalent subtypes in favour of the less prevalent ones. The unbalanced compendium in contrast contains all the available data. Furthermore models per subtype were paired with untyped models constructed on a mixture of subtypes with the latter being evaluated using the exact same samples that were used for evaluating the subtyped models. "That allows a realistic and fair comparison between the models. Our protocol offers a way to deal with the unbalance in datasets."

Controversial conclusions
"Comparing all our different models showed that predictors based on subtyped models outperform the untyped predictors. Subtyping clearly makes sense. And for each individual subtype, you should use all data available, because the more data you put in, the better your model." Moerland emphasizes that their work is not only of interest for bioinformaticians, but they came up with interesting biological results as well. "One of our results is that for predicting the risk of metastasis, there is no need to distinguish between the subtypes luminal A and luminal B. These subtypes can just as well be combined." Moerland realizes that the precise definition of relevant molecular subtypes is still a controversial subject. "It was the main reason that our work was rejected elsewhere. Clearly, those reviewers belong to the opposing side." The debate on predictive profiling continues.

Reference An evaluation protocol for subtype-specific breast cancer event prediction
Sontrop HMJ, Verhaegh WFJ, Reinders MJT, Moerland PD
PLoS One, 2011;6(7):e21681

A new model to study the human gut bacterial metabolism of starch

Fri, 09 Sep 2011 13:54:00 +0200

Hans van Beek (VU) and Jaap Heringa (VU), both NBIC Faculty members, developed a new model of human faecal microbiota. In their paper in Benef Microbes they explore human gut bacterial metabolism of starch using a combined analytical and computational modelling approach for metabolite and flux analysis. The work was accomplished in close collaboration with Albert de Graaf (TNO) who provided the experimental data and microbial metabolism expertise. Reference

Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota in vitro.
Binsl TW, De Graaf AA, Venema K, Heringa J, Maathuis A, De Waard P, Van Beek JH
Benef Microbes. 2010 Nov 1;1(4):391-405

ss-Tea to identify specific ligand binding residues

Fri, 09 Sep 2011 09:40:00 +0200

NBIC Faculty members Jacob de Vlieg and Wynand Alkema present ss-TEA, a method to identify specific ligand binding residue positions for any receptor, predicated on high quality sequence information.

The method is also available online via GPCRDB at http://www.gpcr.org/7tm/. Reference
ss-TEA: Entropy based identification of receptor specific ligand binding residues from a multiple sequence alignment of class A GPCRs.
Sanders MP, Fleuren WW, Verhoeven S, van den Beld S, Alkema W, de Vlieg J, Klomp JP
BMC Bioinformatics. 2011 Aug 10;12(1):332

Life Sciences Pre-Seed Grant: Call open for submission

Mon, 05 Sep 2011 14:23:00 +0200

The eighth round of the Life Sciences Pre-Seed Grant, is now open for submissions. All Life Sciences researchers thinking about starting up a company are invited to submit an application. The Life Sciences Pre-Seed Grant is financed and supported by the Netherlands Genomics Initiative (NGI), Life Sciences and Health Innovation Program (LSH) and ZonMw (The Netherlands Organisation for Health Research and Development). The Life Sciences Pre-Seed Grant offers a great opportunity for applied researchers associated with a Dutch university or research institution. Worth up to € 250,000, it offers superb prospects for those looking to exploit their fundamental research commercially by starting up a new business. Apart from the obvious cash injection, being awarded a Pre-Seed Grant sets the scene for creating a commercial platform for exploiting your research. The grant may be used to validate your research, perform (further) clinical or pre-clinical research, or to fund practical issues concerning starting up a company, such as acquiring knowledge on legal or IP aspects, or for technology transfer. The final objective is to ensure there is an effective and powerful business plan in place, making the new company viable, profitable and attractive to possible investors. Go to www.preseedgrant.nl. There you will find all the information you need for checking your eligibility for the grant and for submitting an application. Submission deadline: 11 October 2011.

Using large scale computing facilities for Biobanks

Mon, 05 Sep 2011 13:16:00 +0200

The Netherlands have 150 biobanks with over 400,000 samples in total. To exploit these billions worth of material they are now embarking on large scale genetic profiling. An example is the highly visible Genome of the Netherlands project that will sequence the DNA of 750 Dutch individuals completely to elucidate the genetic diversity in the Dutch population, and to impute this new information onto existing more sparse genetic information of 100.000 Dutch individuals. However, the data handling and computational needs are enormous and Dutch Institutes are struggling to effectively use the hardware infrastructures available.

The e-BioGrid subproject on Biobanking will overcome this barrier by interfacing the data processing tools used in biobanking to the existing BiGGrid infrastructure and by supporting the Dutch biobanking community to deploy these tools for their large data and processing challenges.

Looking for an alternative

Mon, 22 Aug 2011 15:25:00 +0200

The genetic code is universal. No matter how different organisms are, the combination of three nucleic acids (C, A, T, G) that encodes a specific amino acids or a stop codon is always the same.

But that assumption is not universally true. Already quite some alternative genetic codes have been encountered in bacteria, organelles, viruses and even eukaryotic nuclei. "Of all the published genetic sequences so far, almost 1% contains an alternative genetic code, but most researchers in large scale sequencing projects simply assume that they are dealing with the standard code", says NBIC faculty member professor Martijn Huynen of the Centre for Molecular and Biomolecular Informatics (CMBI) at Radboud University Nijmegen. His group developed a new tool, FACIL, that allows for a fast and reliable check of raw data on the presence of an alternative genetic code (Dutilh et al, Bioinformatics, 2011, June 8).

Protein domains
"Our basic assumption is that the presence of proteins is much more universal than the genetic code. FACIL looks for homology in protein domains instead of comparing the sequence to all known proteins. That explains why FACIL is much faster than other methods", Huynen explains. "Next to being fast, FACIL also provides an indication on the reliability of its prediction, which is the other main characteristic of this new tool." FACIL is already available for use and does not require a lot of pre-processing of the raw data, Huynen points out. "FACIL can and should be employed in data analysis as early as possible." His personal main interest in FACIL is the potential to discover new alternative codes. "We are really interested in assessing how universal the genetic code is. Metagenomics data provides us with that opportunity for the first time and the tool is ready. All we need are the discoveries."

FACIL is available as a web-based service at http://www.cmbi.ru.nl/FACIL
or as a stand-alone program

FACIL: fast and accurate genetic code inference and logo
Duthilh BE, Jurgelenaite R, Szklarczyk R, van Hijum SA, Harhangi HR, Schmid M, de Wild B, Françoijs KJ, Stunnenberg HG, Strous M, Jetten MS, Op den Camp HJ, Huynen MA
Bioinformatics, 2011, June 8

MixupMapper checks your data

Mon, 22 Aug 2011 15:03:00 +0200

In spite of protocols, regulations and experienced staff, scientific research is as prone to human errors as are other professional fields. Sometimes, errors are clearly visible and can be easily corrected. But when confronted with large-scale, complex datasets, it is not immediately clear if, for example, samples have been mislabelled or swapped. Thanks to the work of PhD-student Harm-Jan Westra and colleagues at the University of Groningen, researchers can now employ the MixupMapper to check their results for any sample mix-ups (Westra et al., Bioinformatics, 2011 June 7).

Swaps in GWAS
The reason for developing the MixupMapper algorithm was a serious mistake made in their own lab during a genome-wide association study (GWAS) into gene expression levels, says joint last author Lude Franke. "That got us thinking about a way to track down sample swaps in datasets and correct them post hoc. Once we had established the MixupMapper, we wondered about the frequency of sample swaps in general and decided to test our algorithm on five publicly available genetical genomics datasets. We detected sample mix-ups in four of these datasets. In one dataset, we found that 23% of the samples were swapped!" Correcting mistakes is not only the right thing to do, it greatly improves the quality of your results, Franke explains. "Firstly, mix-ups create noise, so by removing them you enhance to overall signal-to-noise ratio. Secondly, by correcting mix-ups, true information is added which further boosts your findings." In their paper, the researchers state that correcting for mix-ups led to a significant increase in the number of cis-eQTLs (expression quantitative trait loci) identified and that it could substantially increase the explained heritability and power to detect genetic effects in GWAS on complex phenotypes.

Spell-checker
Simply put, MixupMapper checks whether a generated phenotype (in this case: a gene expression level is the phenotype) corresponds to what could be expected from the associated genotype. "A correlation between genotype and phenotype can be interpreted in two ways, which implies that you can also deduct a genotype from a phenotype to see if it corresponds to the actual genotype. That is the essence of the MixupMapper", explains first author Harm-Jan Westra. This also implies that some prior knowledge on genotype-phenotype relations is necessary to be able to perform this check. Franke adds: "The method only works for datasets that contain large numbers of phenotypes. The algorithm compares predicted outcomes based on SNPs to measured values and if these seriously diverge then a sample mix-up is a plausible explanation." He therefore urges researchers to include the MixupMapper in every data analysis involving both gene expression levels and genotype data. "It is like a spell-checker. The MixupMapper is really a quality control tool."

MixupMapper is available at: http://www.genenetwork.nl/mixupmapper

MixupMapper: correcting sample mix-ups in genome-wide datasets increases power to detect small genetic effects
Westra HJ, Jansen RC, Fehrmann RS, te Meerman GJ, van Heel D, Wijmenga C, Franke L
Bioinformatics, 2011, June 7

Meaningful variation

Thu, 11 Aug 2011 11:20:00 +0200

In the world of functional genomics (e.g. transcriptomics, proteomics, metabolomics), data analysis knows no shades of grey. Either you opt for univariate analysis – in which the focus is on a single gene or metabolite – or you look at all variables in one go, i.e. the multivariate approach. "Univariate analysis is attractive because there are many methods available and the interpretation is relatively easy, but correlation between different biological actors is left out. You loose a lot of valuable information that way", says NBIC faculty member professor Age Smilde of the Biosystems Data Analysis group at the Swammerdam Institute of Life Sciences (University of Amsterdam). "With multivariate analysis, all correlations are included, but here the drawback is that the interpretation becomes difficult. We have therefore come up with a middle course, the simplivariate models."

Fluttering
The leading idea behind the simplivariate approach is that a substantial part of the variation exhibited in the data does not offer any information on the biology of the system. Smilde explains: "Many variables are simply 'fluttering'. They vary, but their variation is not connected to an underlying biological phenomenon that is relevant to the biological research question. This type of variation is what we call non-informative. With our simplivariate approach, we can identify groups of variables that show coherent behaviour, which is an important clue to potentially underlying biological processes. Employing our algorithm is a first step towards tackling a complex dataset in a more efficient manner."

Coherence
To determine what type of behaviour should be considered 'coherent', close involvement of biologists is essential, according to Smilde. "You need continuous discussions with the biologist to learn for example how many biological phenomena they expect to see to get an idea of whether your analysis is making any sense. Also, they need to inform you on how strong a correlation needs to be to be considered relevant. Based on this information, the bioinformaticians can choose the right model to apply. There are several possibilities in our approach." The recently published algorithm (Saccenti et al., PLoS One, 2011) builds on earlier work into simplivariate models. "We have incorporated a new model and both the statistics and the algorithm itself have been improved", says Smilde. Right now, work is ongoing within the Data Support Platform of the Netherlands Metabolomics Centre in collaboration with NBIC, in which Smilde is also involved, to turn the simplivariate algorithm into a robust and user-friendly tool. Smilde expects this new tool to become available within 6 months - 1 year from now.

For those interested in the meantime, check the paper:
Simplivariate models: uncovering the underlying biology in functional genomics data
Saccenti E, Westerhuis JA, Smilde AK, van der Werf MJ, Hageman JA, Hendriks MM
PLoS One 2011;6(60):e20747

Peeling the potato

Thu, 11 Aug 2011 09:32:00 +0200

Started in 2006 and completed mid-2011 with a publication in leading science journal Nature: the sequencing of the potato genome. Roeland van Ham, currently vice-president Bioinformatics and Modeling with Dutch biotech firm Keygene N.V., has been involved in the international project right from the start. At the time, he was group leader bioinformatics and head of the sequencing facility at Wageningen University and Research Centre, one of the leading parties in the Potato Genome Sequencing Consortium. When asked about the role of bioinformatics in this undertaking, he doesn't hesitate. "Bioinformatics takes the key position in such a project. We ensure that the biologists can actually make sense of the data generated by the sequencers." This required however dealing with numerous technical challenges, not only caused by the sheer volume of the datasets generated, but also due to the specific characteristics of the potato genome itself.

Van Ham: "Especially the assembly phase of the project, in which the genome sequence is reconstructed from the smaller read-outs produced by the sequencers, proved really difficult and time-consuming due to the fact that potato is heterozygous. At the same time, these problems stimulated the development of new assembly tools. Within NBIC, I then headed the BioAssist Next Generation Sequencing taskforce and in the potato project, we could benefit from the taskforce's work on de novo assembly algorithms." In spite of the many hurdles they faced, no real breakthroughs were achieved (or required) from a bioinformatics perspective. But that does not imply that it was just a standard operation, Van Ham points out. "No, it was really cutting-edge bioinformatics work from start to finish. We came up with a lot of new tools and approaches, for example on assessing the quality of next generation sequencing data and on new ways to process raw data and genomes by k-mer analysis." Meanwhile, he has left academia, but food crops are still on his daily professional menu: a paper on the sequence of the tomato genome and a comparison to potato is about the be submitted, he reveals. Genome sequence and analysis of the tuber crop potato
The Potato Genome Sequencing Consortium
Nature, 2011 July 14;475(7355):189-95

New CytoscapeRPC plugin available

Thu, 11 Aug 2011 08:47:00 +0200

Cytoscape is widely used by biologist and bioinformaticians to visualize data in networks. Until recently, with each new or adjusted experiment, researchers had to create the visualization again from scratch. A tedious process that involved a lot of repetitive actions. Thanks to the new CytoscapeRPC plugin, developed by NBIC scientific programmer Jan Bot (research group of professor Marcel Reinders, Delft University of Technology), researchers no longer need to 'leave' their own work environment, but can create, modify and re-use scripts in their language of choice. This way, using Cytoscape has become much more efficient and user-friendly. The plugin was published June 27, 2011 in Bioinformatics.

Although the experiences within the Reinders-group were the driver behind developing the new plugin, it quickly became clear that others were looking for such a tool as well. "On the Cytoscape mailing list, people asked whether a tool was available that would allow them to do exactly what we were planning to deliver with our plugin", Bot says. "We started collaborating with these interested users and one of them, Paul Shannon, has meanwhile used our plugin as the basis for a completely new module in R. It is really nice to see that your tool is used by others in that way and that they create new possibilities that we didn't foresee." Exactly because of this collaboration with other users, the plugin boasts a very broad spectrum of functions within Cytoscape that are supported and can be queried. Bot: "Getting input from external users broadened our development work."

So far, the plugin has been downloaded over 200 times. Also interested? The plugin can be easily installed through the Cytoscape plugin manager. In addition, CytoscapeRPC is also available through the NBIC wiki.

Galaxy Community Conference 2011 hosted by NBIC

Mon, 30 May 2011 13:24:00 +0200

The 2011 Galaxy Community Conference was held 25-26 May, at the Conference Centre De Werelt in Lunteren, The Netherlands. The conference was co-organized and hosted by the Netherlands Bioinformatics Centre (NBIC). Advantages such as an open source license, simple user interface, easy extensibility, and abundant bioinformatics tools make Galaxy a good candidate to process the biological data that is being generated at an ever increasing speed. Galaxy has been used as the main integration platform in the NBIC BioAssist program to leverage the bioinformatics strength of various member groups. The conference featured two full days of presentations and discussion on extending Galaxy to use new tools and data sources, deploying Galaxy at your organization, and best practices for using Galaxy to further your research. The event drew almost 150 participants from 19 countries on six continents. Among them, more than 30 people were from NBIC and NBIC affiliated Dutch institutions. A small number of participants did not make their trips due to the volcano ash cloud over several northern European countries. However, thanks to Skype and Twitter, they were able to present their talks remotely and follow the discussions real-time (with more than 600 tweets). Barend Mons (NBIC scientific director) opened the NBIC sponsored bar night on May 25th with a warm welcome speech. The pleasant atmosphere together with famous brands of Dutch beer created an unforgettable evening for all conference guests and apparently have paved ways for several future collaborations. Read the tweets (#usegalaxy ) on May 25-26 to get an impression by the participants of the conference. The videos of the conference are now available online at the NBIC video channel. Read also about the Galaxy Community Conference at Genomeweb.com.

NBIC Faculty in leading positions in Open PHACTS consortium

Fri, 27 May 2011 11:49:00 +0200

A new consortium of European organisations unite to support next generation drug discovery by providing a single view across data sources, bringing the semantic web to drug discovery. The Open PHACTS consortium, funded by the Innovative Medicines Initiative, will reduce the barriers to drug discovery by applying semantic technologies to available data resources, creating an Open Pharmacological Space.
NBIC Faculty members from the Leiden University Medical Centre, VU Amsterdam and Maastricht University are in leading positions in this consortium.

Prize winners at NBIC conference

Thu, 28 Apr 2011 16:20:00 +0200

The NBIC conference programme included several competitions. A jury of the RSG Netherlands judged the oral presentations to choose the best lecture of the conference. Fiona Nielsen, PhD student at the Centre for Molecular and Biomolecular Informatics (CMBI, UMC St Radboud Nijmegen) won the prize with her lecture 'CATCHprofiles: Clustering and Alignment Tool for ChIP profiles'. Two prizes were available for the poster presentations. One prize was offered by the BioInformatics Industrial User Platform (BIUP), which organised a satellite meeting during the NBIC conference. They judged the posters from a industrial point of view. Patrick Koks (Wageningen UR) received the prize for his poster about 'eBiomics: an e-Learning environment on bioinformatics for life-scientists'. The other poster prize was given to the poster which was "liked" the most by the conference participants, who could show their appreciation by "Facebook like stickers". Wouter Meuleman (NKI/TUD) found the most stickers on his poster about 'Dynamics and evolution of genome – nuclear lamina interactions'. The third competition was the application showcase, where researchers could show the applications they developed. Three out of ten were selection for the final presentations on stage:

Bas Vroling (CMBI) presented GPCR-specific PDF reader
Miranda Stobbe (AMC) presented JamboreeCards
Kasper Dinkla (TU Eindhoven) presented BiotaViz

With 92 votes the audience selected the winner: Bas Vroling!

6th edition of the NBIC conference attracted over 200 participants

Thu, 28 Apr 2011 16:11:00 +0200

More than 200 people visited the six^th edition of the NBIC conference, April 19-20. The plenary programme included keynote lectures, workshops and several competitions. Satellite meetings were organised by the PhD students network RSG Netherlands, the BioInformatics Industrial User Platform (BIUP) and the Netherlands Society on Biomolecular Modelling (NSBM). All these groups together created a lively atmosphere, inside (and outside) the conference venue 'De Werelt' in Lunteren. For a first impression visit the NBIC page on facebook. A full photo impression by a professional photographer is also available on the conference website.

NBIC Young Investigator Award 2011

Thu, 28 Apr 2011 15:52:00 +0200

The winner of the NBIC Young Investigator Award 2011 is Dr. Yang Li, Groningen Bioinformatics Centre,University of Groningen. She is awarded with a cash prize of 2.500 Euro funded by NBIC BioRange and BioWise programmes. Yang Li has received the NBIC Young Investigator Award 2011 for her PhD research. Her PhD thesis shows a beautiful mix of bioinformatics method development and biological application, and as such the work is squarely positioned in mainstream bioinformatics, showing the essentiality of the field. The jury, chaired by Jaap Heringa, was further impressed by the novel methodological developments an innovation in Li's work, while her work is also highly interdisciplinary in that she has closely collaborated with biomedical experts. The award ceremony took place on the NBIC Conference (April 20th, 2011) and was followed by a honorary lecture by Yang Li about Generalized Genetical Genomics -Advanced methods and applications.

CMBI and Organon excel in global GPCR modeling competition

Mon, 28 Feb 2011 17:11:00 +0100

A team of bioinformaticians from the Centre for Molecular and Biomolecular Informatics (CMBI, Radboud University Nijmegen Medical Centre) and Department of Molecular Design and Informatics (MSD/Organon) recently participated in a prestigious world-wide challenge in predicting the binding orientation and interactions of small molecule inhibitors to two different G protein-coupled receptors (GPCRs). In a joint effort Marijn Sanders, Bas Vroling, Jan Klomp, Jacob de Vlieg and Sander Nabuurs used computer simulations to predict the three-dimensional structure of these complexes, prior to the release of the experimentally determined crystal structures. Excellent results were obtained for both the dopamine D3 receptor (DRD3), a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease, as the CXCR4 receptor, involved in HIV infection and cancer. For the DRD3 receptor, out of over a hundred models entered by 32 internationally renowned groups, all five submitted predictions ranked in the top 10 best models with the best model ranking second. Not only was the CMBI/MSD team the only with multiple models in the top 10, they were also the only team to succeed in correctly ranking the submitted predictions. The group’s most accurate prediction for CXCR4 was ranked 14th out of the in total 103 submitted models. Remarkably, the best prediction for this target was generated by another Dutch team: the Medicinal Chemistry group of VU University Amsterdam. Both also collaborate in the Dutch Top Institute Pharma GPRC forum. To generate these successful predictions, the joint CMBI/MSD team utilized in-house developed modeling approaches, combining the protein-based pharmacophore modeling program Snooker (developed by Marijn Sanders and Jan Klomp as part of the Dutch Top Institute Pharma GPRC forum) with the flexible docking program Fleksy (which originated from an NBIC project, and is currently further developed in an NWO-Veni project of Sander Nabuurs).

Participate in the NGI Venture Challenge Spring 2011!

Tue, 18 Jan 2011 09:32:00 +0100

Thinking of starting up a company in Life Sciences? Got a great idea but not sure how to commercialise it? Then, if you're up for it, the Venture Challenge may be exactly what you're looking for. The Netherlands Genomics Initiative warmly invites all Life Sciences researchers to participate in the NGI Venture Challenge Spring 2011. Pave your way to success
The Venture Challenge is a ‘must-do’ opportunity for all aspiring Life Sciences entrepreneurs, it is the way to receive coaching and advice on essential elements of setting up a business, thereby paving the way for your future success. It is also superb preparation for the next stage: acquiring financing, such as the Life Sciences Pre-Seed Grant. In two 3-day workshops, the facilitators and other ‘competing’ teams will challenge you to focus your business idea to create optimal customer value, and you will learn to pitch your business case. At the end of the Challenge, the team with the best venture plan and pitch is awarded € 25,000. Apply for the NGI Venture Challenge by filling in the enclosed Venture Proposal Form - before 1 March 2011, 12:00 hrs - and send it to: info@venturechallenge.nl If your idea passes the pre-screening, you and your team are in for a fascinating experience. For additional information and an overview of the important dates, please check: www.venturechallenge.nl

Boolean modelling sheds light on regulatory circuits

Thu, 16 Dec 2010 15:35:00 +0100

Pairs of almost similar genes have long been thought to act as back up for each other. But in their paper published in Cell on December 10, shared first authors Patrick Kemmeren and Sake van Wageningen and their colleagues from the group of Frank Holstege (NBIC /UMC Utrecht) show that such gene pairs actually form regulatory circuits that influence different combinations of cellular processes. This way, an organism can efficiently couple or decouple processes, for example when dealing with altered environmental conditions. The ability to use genetic information in such an efficient way may also explain the high level of conservation of some of these gene pairs during evolution. The group analysed 150 deletion mutants of kinases and phosphatases in baker's yeast (Saccharomyces cerevisiae) using DNA microarrays to study relationships between phosphorylation-based signalling pathways. They particularly focused on genetic buffering relationships such as redundancy. To this end, they selected double mutants that exhibited a markedly different effect on growth compared to the effect of each single mutant. This resulted in the identification of three types of genetic buffering mechanisms: mixed epistasis, complete redundancy and quantitative redundancy.

Modelling the module
In mixed epistasis there is only partial overlap in function between the two genes and their coupling usually involved additional regulatory mechanisms such as repression of one by the other. This allows the gene pair to operate as a regulatory module that can control different processes under different circumstances. To unravel the mode of action of such a module, the researchers zoomed in on the FUS3-KSS1 kinase pair. "Our starting point was to define the regulatory module as a model consisting of four nodes: two regulators and two responses. We defined a number of boundary conditions, for example that each node was controlled by a maximum of two inputs and that there should always be at least one route to the responses, R1 and R2", Patrick Kemmeren explains. "This resulted in 794,176 possible models. Using Boolean modelling, Philip Lijnzaad reduced these to 106 models that would actually lead to the minimal mixed epistatic effect. Further pruning left us with 28 root models that all exhibit the experimentally observed mixed epistasis." Although the modelling concentrated on one particular gene pair, the approach revealed important information on how gene pairs with only partial overlap in function can operate as an effective regulatory module that has the ability to act as a multi-process control unit. In turn, this would explain their evolutionary conservation.

Sake van Wageningen, Patrick Kemmeren, et al., Functional Overlap and Regulatory Links Shape Genetic Interactions between Signaling Pathways, Cell, 143, 991-1004, December 10, 2010 http://www.cell.com/abstract/S0092-8674(10)01301-2

BioCatalogue: The 'Yellow Pages' of web services

Mon, 21 Jun 2010 17:10:00 +0200

The continuous flow of newly developed web services is of course great news for anyone working in bioinformatics and computational biology. But the overwhelming array of possibilities makes it also hard to identify the web service that suits your needs best. To assist researchers in their search for web services, the group of Carole Goble at the University of Manchester (UK) and the European Bioinformatics Institute have developed BioCatalogue – a common interface for registering, browsing and annotating web services.

One of the co-authors of the BioCatalogue-paper is Marco Roos (Leiden University Medical Centre/University of Amsterdam/NBIC), who acts as a liaison between NBIC and the Goble group. "BioCatalogue offers an overview of web services that are relevant to the life sciences community", Marco explains. "Right now, main sources for BioCatalogue are EMBRACE and Taverna, but as users start registering tools and web services themselves, the scope of BioCatalogue will expand. " He emphasises the role users play in making an interface like BioCatalogue work. "In the end, websites are made by the users. Social community mechanisms are driving the development and the relevance of a website. Your additions, feedback and annotations are important to other users and vice versa."

Feedback
He describes his own role in the project as that of a 'super-user'. "The developers of BioCatalogue are strongly user-oriented. They operate in short development cycles that immediately incorporate user feedback. Working with the different versions of BioCatalogue in my own research, I provided feedback that they used as input for the next development cycle. Pieter Neerincx of the NBIC proteomics platform also contributed feedback as one of the curators." This interactive approach is beneficial for both developers and users, says Marco. "They make the best software, so that we can get the best software."

Taverna plug-in
To increase easy of use, there is no shortage of plans for further development of BioCatalogue. Marco: "I am a Taverna user and we are currently testing a Taverna plug-in that enables you to use BioCatalogue as the search tool within Taverna. What I already like is that the search result presents you with a number of suggestions to explore further." Other plans include a combination of BioCatalogue and MyExperiment, monitoring web services to notify users when changes occur and the possibility to run services in BioCatalogue.

Protein structure bioinformaticians unite

Mon, 12 Apr 2010 16:37:00 +0200

Providing a platform for researchers active in protein structure bioinformatics in the Netherlands - that is in short the goal of the brand new Netherlands Society on Biomolecular Modelling (NSBM). Following the successful Protein Structure Bioinformatics meeting on March 1st at the CMBI in Nijmegen, a few enthousiastic researchers discussed the possibility of setting up a more structured format for contacts within the protein structure bioinformatics field in the Netherlands. The discussions quickly led to the idea of a new society, the NSBM, which is supported by NBIC. The NSBM aims to become an active discussion partner in the various policy-making boards that are relevant to the protein structure bioinformatics field. Through organising regular meetings, the NSBM plans to stimulate contacts between researchers and sharing of ideas. The formal process of founding the society is ongoing. The board of the NSBM will at first consist of Gerry Nicolaes (Maastricht University, chairman), Gert Vriend (CMBI, Nijmegen), Rob Hooft (NBIC, Nijmegen) en Tassos Perakis (Netherlands Cancer Institute, Amsterdam). On September 20, the next meeting on protein structure bioinformatics, entitled "Mutations in proteins: structure, function and dynamics", is organised at the CMBI in Nijmegen.

Lude Franke wins NBIC Young Bioinformatician Award 2010

Mon, 22 Mar 2010 13:32:00 +0100

Dr. Lude Franke of the University of Groningen has won the first edition of the NBIC Young Bioinformatician Award. NBIC yearly presents this award for a young researcher who has significantly contributed to bioinformatics or the bioinformatics community in the Netherlands. Lude was nominated by Ritsert Jansen for his excellent work during his PhD research which resulted in 24 papers (including 4 in Nature Genetics and 4 in the American Journal of Human Genetics) and a cum laude graduation. In close collaboration with researchers in biology and medicine he has developed novel bioinformatics methods for the identification of susceptibility genes in complex diseases. Lude will be awarded with a cash prize of 2.500 Euro. The prize winning ceremony will take place at the NBIC conference on March 30th in Lunteren followed by a lecture by the winner.

Participate in the NGI Venture Challenge Spring 2010!

Sun, 07 Feb 2010 14:04:00 +0100

The Netherlands Genomics Initiative invites all Life Sciences researchers to participate in the NGI Venture Challenge Spring 2010. The Venture Challenge is an opportunity for all aspiring Life Sciences entrepreneurs, it is the way to receive coaching and advice on essential elements of setting up a business. It also prepares you for the next stage: acquiring financing, such as the Life Sciences Pre-Seed Grant. In two 3-day workshops, the facilitators and other ‘competing’ teams will challenge
you to focus your business idea to create optimal customer value, and you will learn
to pitch your business case. At the end of the Challenge, the team with the best venture plan and pitch is awarded €25,000. You can apply for the NGI Venture Challenge by filling in the Venture Proposal Form - before 26 March 2010, 12:00 hrs - and send it to: info@venturechallenge.nl

For the Venture Proposal Form and additional information and an overview of the important dates, please check www.venturechallenge.nl.

More than 1000 users downloaded StatQuant

Fri, 05 Feb 2010 14:11:00 +0100

This week NBIC has registered the 1000st download of the software tool StatQuant from the NBIC Gforge software repository. StatQuant offers a set of statistical tools to process, filter, compare and represent data from several quantitative proteomics software packages. It is developed in a collaborative project of NBIC and the Netherlands Proteomics Centre (NPC). Mass spectrometric protein quantitation has emerged as a high-throughput tool to yield large amounts of data on peptide and protein abundances. Currently differential abundance data can be calculated from peptide intensity ratios by several automated quantitation software packages available. There is, however, still a great need for additional processing to validate and refine the quantitation results. The software tool StatQuant offers a set of statistical tools to process, filter, compare and represent data from several quantitative proteomics software packages such as MSQuant. StatQuant offers the researcher post processing methods to achieve improved confidence on the obtained protein ratios. More information can be found at the NBIC Wiki: https://wiki.nbic.nl /index.php?title=StatQuant StatQuant can be downloaded from the NBIC software repository: https://gforge.nbic.nl/projects/statquant/

NGI sponsors Postdoc Retreat

Mon, 18 Jan 2010 14:35:00 +0100

The Postdoc Career Development Initiative (PCDI) supports postdocs and
final year PhD students at career orientation and realising young researchers' potential. On 21-23 April 2010, PCDI's best known event, the annual Postdoc Retreat, will be held for the 4th time. This three-day event is dedicated to career development: identifying your skills and talents, improving your transferable skills, orientation of career paths in Life Sciences, both within and outside academia and focussing on the future. The programme includes keynote lectures, training sessions, workshops and meet & greets with potential employers. The Postdoc Retreat is a career development event unique in the Netherlands. Because it is exclusively open to postdocs and final year PhD students in Life Sciences, you can expect activities tailored to be immediately relevant to your career stage. It has been attended by over 300 early career scientists, including researchers from abroad! The Netherlands Genomics Initiative aims to actively encourage its young researchers to participate: 1000 euro per person has been made available for NGI funded researchers to cover a great share of the 1200 euro registration fee. SoFoKles will finance the remaining 200 euro upon demonstration of a dialogue with the P.I./supervisor about career development i.e. handing in this completed form. Send a scan of the completed and signed registration form to info@pcdi.nl, cc to donselaar@genomics.nl. Attention! NGI will fund 25 NGI-funded postdocs/final year PhD students to register for Postdoc Retreat 2009 on a first come, first served basis! For more information: visit website below.

Life Sciences Pre-Seed Grant: Call open for submissions

Mon, 18 Jan 2010 09:53:00 +0100

The fifth round of the Life Sciences Pre-Seed Grant, is now open for submissions. All Life Sciences researchers thinking about starting up a company are invited to submit an application. The Life Sciences Pre-Seed Grant is financed and supported by the Netherlands Genomics Initiative (NGI), Life Sciences and Health Innovation Program (LSH) and ZonMw (The Netherlands Organisation for Health Research and Development). The Life Sciences Pre-Seed Grant offers a great opportunity for applied researchers associated with a Dutch university or research institution. Worth up to € 250,000, it offers superb prospects for those looking to exploit their fundamental research commercially by starting up a new business.

Being awarded a Pre-Seed Grant sets the scene for creating a commercial platform for exploiting your research. The grant may be used to validate your research, perform (further) clinical or pre-clinical research, or to fund practical issues concerning starting up a company, such as acquiring knowledge on legal or IP aspects, or for technology transfer. The final objective is to ensure there is an effective and powerful business plan in place, making the new company viable, profitable and attractive to possible further investors.

Go to www.preseedgrant.nl. There you will find all the information you need for checking your eligibility for the grant and for submitting an application. Submission deadline: 2 March 2010, 15:00 h.

Call for papers: Transactions on Computational Systems Biology

Mon, 21 Dec 2009 11:40:00 +0100

LNBI Transactions on Computational Systems Biology calls for paper submissions for a special issue on “Computational Models for Cell Processes”. Original papers and surveys are sought in all areas that relate to the relevance and potential of formal methods and computational modeling and simulation in systems biology. Of special interest are contributions that present biological processes requiring special tools and techniques that have not been investigated so far in the context of formal methods, as well as extensions of already existing formalisms introduced to improve their applicability in the life sciences. Topics of interest include, but are not limited to:

Formal models for cellular pathways
Qualitative biological modeling
Quantitative formal methods
Theoretical comparison of formalisms for biological processes
Biologically-inspired extensions to formal methods and concurrency
theory
Differential, discrete and/or stochastic modeling languages
Reconstruction of biological networks based on empirical data
Decomposition and modularization of large biological networks
Applications of formal methods and computational modeling
Membrane systems as a modeling platform

Important dates:

Paper submissions: March 31, 2010
Acceptance notification: June 30, 2010
Final papers: August 31, 2010

NBIC PhD Course Algorithms for Biological Networks now open for registration

Fri, 13 Nov 2009 10:44:00 +0100

The PhD Course Algorithms for Biological Networks of the NBIC PhD School will take place on 11-15 January 2010 in Delft. More information about the content of the course can be found at the course website. Registration is now open.

NBIC@the museum

Tue, 10 Nov 2009 15:55:00 +0100

During 'Oktober Kennismaand' (October: Month of Knowledge), NBIC was present at Scientific, a science festival hosted by Science Centre NEMO in Amsterdam. The festival was themed 'Travelling into the unknown' and focused on the study of things that are for example very far away, happened in the past or are extremely small, such as DNA. NBIC and the Cancer Genomics Centre were invited by NEMO to demonstrate their respective 'DNA-labs on the road' (in Dutch: Reizende DNA Labs) to the audience, but with an additional request for NBIC to focus its bioinformatics@school material on the younger children aged 6-12. Candy molecules
NBIC presented three computer-based demo's that stimulate children to think about DNA in a very playful manner. "With the DNA Balance, you can calculate how many grams of DNA you have in your body based on characteristics like age, height and weight", explains Hienke Sminia, officer education at NBIC. "We also presented a game called DNA Inclusive, in which the children have to decide whether familiar products like apple juice or peanut butter contain DNA or not. And in the third demo, we used the Yasara programme to show the children very small molecules, which they had to build using candy and cocktail sticks." Expand audience
According to Hienke, the NBIC demo's were a big hit with the children. Not surprisingly, building molecules out of candy was especially popular. "Of course, at this young age they do not completely understand what they are doing, but they were already very good at the DNA Inclusive game. And they do realise that the world around them is made up out of tiny little particles." This type of spin-off from the bioinformatics@school project is definitely something that NBIC will actively pursue, says Hienke. "We are currently working out the best way to expand our audience and also include primary school pupils in our bioinformatics@school activities." Suited for adults
Next to presenting bioinformatics to children and teens, NBIC also readily springs to action when it comes to 'educating' adults. Recently, NBIC was present during a lecture on genetic descent organised by the Centre for Society and Genomics at the Boerhaave Museum in Leiden. The various demo's are definitely suitable for adults as well, says Hienke. "They are also curious to learn how much DNA they carry around in their body." All NBIC activities relating to education and public communication are regularly posted on the Events calendar.

PathVisio 2.0 released

Mon, 26 Oct 2009 13:12:00 +0100

An elegant new feature of PathVisio 2.0 (http://www.pathvisio.org/) is the ability to import experimental datasets and visualize them on top of biological pathways. Large microarray, proteomics or metabolomics datasets can be explored in a way that is more interesting and understandable than by using just a huge spreadsheet. Microarray reporters will be automatically converted to gene or protein identifiers. Visualization can be customized using gradients, boolean colour rules or coloured icons. Perform over-representation analysis to identify the pathway most affected by experimental conditions. A Visual Tour of new and existing features of PathVisio is available at http://www.pathvisio.org/wiki/VisualTour About PathVisio
PathVisio is a tool for creating and analysing biological pathway diagrams. Stay organized by using PathVisio as a notebook to collect the various bits of information related to a biological research subject. Create images suitable for presentation or publication. Draw pathways, export them to many image formats, annotate them with links to online biological databases such as Ensembl or Entrez gene, and add comments and literature references from Pubmed. PathVisio is fully compatible with WikiPathways (http://www.wikipathways.org/), a wiki where researchers can contribute pathway knowledge. Information for developers
PathVisio has a plug-in interface that allows customization by users to accommodate new analysis types, new visualization methods and new pathway formats. PathVisio is fully open source, and we are always looking for Java developers who are interested in contributing, either to new plug-ins or to the core of the program. Contact us through our mailing list: http://www.pathvisio.org/wiki/MailingLists PathVisio was developed by the BiGCaT Bioinformatics group at Maastricht University, the Netherlands, within the NBIC BioRange programme.

Successful 1st symposium on Systems Genetics

Mon, 12 Oct 2009 14:20:00 +0200

With almost 200 participants, presentations by international experts and young researchers and an open, interactive atmosphere, the first symposium on Systems Genetics, hosted by the University of Groningen on October 1-2 and co-organised by Ritsert Jansen, professor of bioinformatics, was a successful event. Entitled 'Systems Genetics: from man to microbe, from genotype to phenotype', the symposium offered a diverse programme that matched the variety of topics covered by the field itself. Epigenetics, stress responses, the circadian clock, type 2 diabetes, the 1000 dollar genome, systems biology in the mouse – too name just a few of the topics discussed. The plenary programme consisted of presentations by renowned experts in the field mixed with short introductions by young scientists, mostly PhD students. Parallel sessions were organised in the form of master classes, in which an invited speaker and young scientists discussed their research. "That approach worked out really well", says Ritsert Jansen, professor of bioinformatics and NBIC project leader. "I was discussion leader at one of the sessions and usually you have to actively engage the audience, but here I had a very easy job. There was an interactive atmosphere and the discussions really took off." It was explicitly named the first symposium on Systems Genetics, will there be others? "We have not yet made definite plans, but it is certainly worth repeating." NBIC was one of the sponsors of the Systems Genetics symposium. More information on programme and speakers is available at http://www.systemsgenetics.nl/

Distinguished Visiting Scientist

Mon, 05 Oct 2009 14:27:00 +0200

In May 2009, the Netherlands Genomics Initiative (NGI) granted five applications for a Distinguished Visiting Scientist Stipend. NBIC BioRange researcher Prof. Ritsert Jansen received the Stipend to collaborate at Jackson Laboratory in Maine USA. New applications for the NGI Stipend may be submitted by 1 April 2010: http://www.genomics.nl/InternationalActivities/Disting_Stipend.aspx

New CLS projects awarded

Mon, 31 Aug 2009 16:41:00 +0200

The Netherlands Bioinformatics Centre (NBIC), the Netherlands Genomics Initiative (NGI) and the Netherlands Organisation for Scientific Research (NWO Physical Sciences) have launched a second round of the research programme Computational Life Sciences. Recently (June 2009) five new projects have been awarded: The evolution of stochastic heterogeneous networks as bet-hedging adaptations to fluctuating environments
Coordinator: P. Haccou, PhD (Leiden University)

Reverse physiology of the cortical microcircuit
Coordinator: A.R. Houweling, PhD (Erasmus Medical Centre, Rotterdam)

Multi-scale modelling of calcification in scleratinin corals
Coordinator: J.A. Kaandorp, PhD (University of Amsterdam)

The co-evolution of the receptor signalling network of natural killer cells with its ligands
Coordinator: Prof. R.J. de Boer (Utrecht University)

The regulatory network underlying malaria parasite-host interactions
Coordinator: T.M.H. Dijkstra, PhD (Radboud University Nijmegen)

Enlighten your research

Fri, 17 Jul 2009 14:07:00 +0200

Peter Horvatovich (BioRange researcher, University of Groningen) is one of three winners of the competition "Enlighten your research" on dynamics light paths, organised by SURFnet and NWO. Together with Bas van Breukelen (Netherlands Proteomics Centre, and participant in BioRange and BioAssist) he has described a high speed light path network for the Netherlands Bioinformatics for Proteomics Platform. The winners get free access to the light path network and 20.000 Euro to integrate light paths in their research. More information (in Dutch): http://www.surfnet.nl/nl/nieuws/Pages/SURFnetmaaktwinnaarslichtpadenwedstrijdbekend.aspx