NBIC research news

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