Publications by authors named "Martijn van Iersel"

24 Publications

  • Page 1 of 1

The systems biology format converter.

BMC Bioinformatics 2016 Apr 5;17:154. Epub 2016 Apr 5.

EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, CB10 1SD, Cambridge, Hinxton, UK.

Background: Interoperability between formats is a recurring problem in systems biology research. Many tools have been developed to convert computational models from one format to another. However, they have been developed independently, resulting in redundancy of efforts and lack of synergy.

Results: Here we present the System Biology Format Converter (SBFC), which provide a generic framework to potentially convert any format into another. The framework currently includes several converters translating between the following formats: SBML, BioPAX, SBGN-ML, Matlab, Octave, XPP, GPML, Dot, MDL and APM. This software is written in Java and can be used as a standalone executable or web service.

Conclusions: The SBFC framework is an evolving software project. Existing converters can be used and improved, and new converters can be easily added, making SBFC useful to both modellers and developers. The source code and documentation of the framework are freely available from the project web site.
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http://dx.doi.org/10.1186/s12859-016-1000-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820913PMC
April 2016

The Systems Biology Markup Language (SBML) Level 3 Package: Qualitative Models, Version 1, Release 1.

J Integr Bioinform 2015 Sep 4;12(2):270. Epub 2015 Sep 4.

Quantitative methods for modelling biological networks require an in-depth knowledge of the biochemical reactions and their stoichiometric and kinetic parameters. In many practical cases, this knowledge is missing. This has led to the development of several qualitative modelling methods using information such as, for example, gene expression data coming from functional genomic experiments. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding qualitative models, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The SBML Qualitative Models package for SBML Level 3 adds features so that qualitative models can be directly and explicitly encoded. The approach taken in this package is essentially based on the definition of regulatory or influence graphs. The SBML Qualitative Models package defines the structure and syntax necessary to describe qualitative models that associate discrete levels of activities with entity pools and the transitions between states that describe the processes involved. This is particularly suited to logical models (Boolean or multi-valued) and some classes of Petri net models can be encoded with the approach.
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http://dx.doi.org/10.2390/biecoll-jib-2015-270DOI Listing
September 2015

Automatically visualise and analyse data on pathways using PathVisioRPC from any programming environment.

BMC Bioinformatics 2015 Aug 23;16:267. Epub 2015 Aug 23.

Department of Bioinformatics - BiGCaT, Maastricht University, P.O. Box 616, UNS 50 Box 19, 6200, MD, Maastricht, The Netherlands.

Background: Biological pathways are descriptive diagrams of biological processes widely used for functional analysis of differentially expressed genes or proteins. Primary data analysis, such as quality control, normalisation, and statistical analysis, is often performed in scripting languages like R, Perl, and Python. Subsequent pathway analysis is usually performed using dedicated external applications. Workflows involving manual use of multiple environments are time consuming and error prone. Therefore, tools are needed that enable pathway analysis directly within the same scripting languages used for primary data analyses. Existing tools have limited capability in terms of available pathway content, pathway editing and visualisation options, and export file formats. Consequently, making the full-fledged pathway analysis tool PathVisio available from various scripting languages will benefit researchers.

Results: We developed PathVisioRPC, an XMLRPC interface for the pathway analysis software PathVisio. PathVisioRPC enables creating and editing biological pathways, visualising data on pathways, performing pathway statistics, and exporting results in several image formats in multiple programming environments. We demonstrate PathVisioRPC functionalities using examples in Python. Subsequently, we analyse a publicly available NCBI GEO gene expression dataset studying tumour bearing mice treated with cyclophosphamide in R. The R scripts demonstrate how calls to existing R packages for data processing and calls to PathVisioRPC can directly work together. To further support R users, we have created RPathVisio simplifying the use of PathVisioRPC in this environment. We have also created a pathway module for the microarray data analysis portal ArrayAnalysis.org that calls the PathVisioRPC interface to perform pathway analysis. This module allows users to use PathVisio functionality online without having to download and install the software and exemplifies how the PathVisioRPC interface can be used by data analysis pipelines for functional analysis of processed genomics data.

Conclusions: PathVisioRPC enables data visualisation and pathway analysis directly from within various analytical environments used for preliminary analyses. It supports the use of existing pathways from WikiPathways or pathways created using the RPC itself. It also enables automation of tasks performed using PathVisio, making it useful to PathVisio users performing repeated visualisation and analysis tasks. PathVisioRPC is freely available for academic and commercial use at http://projects.bigcat.unimaas.nl/pathvisiorpc.
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http://dx.doi.org/10.1186/s12859-015-0708-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546821PMC
August 2015

PathVisio 3: an extendable pathway analysis toolbox.

PLoS Comput Biol 2015 Feb 23;11(2):e1004085. Epub 2015 Feb 23.

Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands.

PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways. Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application. PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel.
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http://dx.doi.org/10.1371/journal.pcbi.1004085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338111PMC
February 2015

BridgeDb app: unifying identifier mapping services for Cytoscape.

F1000Res 2014 1;3:148. Epub 2014 Jul 1.

Gladstone Institutes, San Francisco, CA 94158, USA.

The BridgeDb app for Cytoscape allows users to map and annotate identifiers of genes, proteins and metabolites in the context of biological networks. The app greatly simplifies the identifier mapping process in Cytoscape by providing a unified interface to different mapping resources and services. The app also provides a programming interface via Cytoscape Commands that can be utilized for identifier mapping by other Cytoscape apps. In this article we provide a technical guide to the BridgeDb app for mapping identifiers in Cytoscape.
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http://dx.doi.org/10.12688/f1000research.4521.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111116PMC
August 2014

Integrated visualization of a multi-omics study of starvation in mouse intestine.

J Integr Bioinform 2014 Mar 28;11(1):235. Epub 2014 Mar 28.

Dept. Bioinformatics - BiGCaT, Maastricht University, The Netherlands.

Our understanding of complex biological processes can be enhanced by combining different kinds of high-throughput experimental data, but the use of incompatible identifiers makes data integration a challenge. We aimed to improve methods for integrating and visualizing different types of omics data. To validate these methods, we applied them to two previous studies on starvation in mice, one using proteomics and the other using transcriptomics technology. We extended the PathVisio software with new plugins to link proteins, transcripts and pathways. A low overall correlation between proteome and transcriptome data was detected (Spearman rank correlation: 0.21). At the level of individual genes, correlation was highly variable. Many mRNA/protein pairs, such as fructose biphosphate aldolase B and ATP Synthase, show good correlation. For other pairs, such as ferritin and elongation factor 2, an interesting effect is observed, where mRNA and protein levels change in opposite directions, suggesting they are not primarily regulated at the transcriptional level. We used pathway diagrams to visualize the integrated datasets and found it encouraging that transcriptomics and proteomics data supported each other at the pathway level. Visualization of the integrated dataset on pathways led to new observations on gene-regulation in the response of the gut to starvation. Our methods are generic and can be applied to any multi-omics study. The PathVisio software can be obtained at http://www.pathvisio.org. Supplemental data are available at http://www.bigcat.unimaas.nl/data/jib-supplemental/ , including instructions on reproducing the pathway visualizations of this manuscript.
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http://dx.doi.org/10.2390/biecoll-jib-2014-235DOI Listing
March 2014

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools.

BMC Syst Biol 2013 Dec 10;7:135. Epub 2013 Dec 10.

Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.

Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models.

Conclusions: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.
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http://dx.doi.org/10.1186/1752-0509-7-135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892043PMC
December 2013

Path2Models: large-scale generation of computational models from biochemical pathway maps.

BMC Syst Biol 2013 Nov 1;7:116. Epub 2013 Nov 1.

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

Background: Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.

Results: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from pathway representations using a suite of freely available software. Data sources include KEGG, BioCarta, MetaCyc and SABIO-RK. Depending on the source data, three types of models are provided: kinetic, logical and constraint-based. Models from over 2 600 organisms are encoded consistently in SBML, and are made freely available through BioModels Database at http://www.ebi.ac.uk/biomodels-main/path2models. Each model contains the list of participants, their interactions, the relevant mathematical constructs, and initial parameter values. Most models are also available as easy-to-understand graphical SBGN maps.

Conclusions: To date, the project has resulted in more than 140 000 freely available models. Such a resource can tremendously accelerate the development of mathematical models by providing initial starting models for simulation and analysis, which can be subsequently curated and further parameterized.
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http://dx.doi.org/10.1186/1752-0509-7-116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228421PMC
November 2013

PathVisio-Faceted Search: an exploration tool for multi-dimensional navigation of large pathways.

Bioinformatics 2013 Jun 1;29(11):1465-6. Epub 2013 Apr 1.

Computer Engineering, University of Maryland, College Park, MD 20740, USA.

Purpose: The PathVisio-Faceted Search plugin helps users explore and understand complex pathways by overlaying experimental data and data from webservices, such as Ensembl BioMart, onto diagrams drawn using formalized notations in PathVisio. The plugin then provides a filtering mechanism, known as a faceted search, to find and highlight diagram nodes (e.g. genes and proteins) of interest based on imported data. The tool additionally provides a flexible scripting mechanism to handle complex queries.

Availability: The PathVisio-Faceted Search plugin is compatible with PathVisio 3.0 and above. PathVisio is compatible with Windows, Mac OS X and Linux. The plugin, documentation, example diagrams and Groovy scripts are available at http://PathVisio.org/wiki/PathVisioFacetedSearchHelp. The plugin is free, open-source and licensed by the Apache 2.0 License.
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http://dx.doi.org/10.1093/bioinformatics/btt146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661049PMC
June 2013

CySBGN: a Cytoscape plug-in to integrate SBGN maps.

BMC Bioinformatics 2013 Jan 16;14:17. Epub 2013 Jan 16.

EMBL - European Bioinformatics Institute, Cambridge, UK.

Background: A standard graphical notation is essential to facilitate exchange of network representations of biological processes. Towards this end, the Systems Biology Graphical Notation (SBGN) has been proposed, and it is already supported by a number of tools. However, support for SBGN in Cytoscape, one of the most widely used platforms in biology to visualise and analyse networks, is limited, and in particular it is not possible to import SBGN diagrams.

Results: We have developed CySBGN, a Cytoscape plug-in that extends the use of Cytoscape visualisation and analysis features to SBGN maps. CySBGN adds support for Cytoscape users to visualize any of the three complementary SBGN languages: Process Description, Entity Relationship, and Activity Flow. The interoperability with other tools (CySBML plug-in and Systems Biology Format Converter) was also established allowing an automated generation of SBGN diagrams based on previously imported SBML models. The plug-in was tested using a suite of 53 different test cases that covers almost all possible entities, shapes, and connections. A rendering comparison with other tools that support SBGN was performed. To illustrate the interoperability with other Cytoscape functionalities, we present two analysis examples, shortest path calculation, and motif identification in a metabolic network.

Conclusions: CySBGN imports, modifies and analyzes SBGN diagrams in Cytoscape, and thus allows the application of the large palette of tools and plug-ins in this platform to networks and pathways in SBGN format.
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http://dx.doi.org/10.1186/1471-2105-14-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599859PMC
January 2013

CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms.

BMC Syst Biol 2012 Oct 18;6:133. Epub 2012 Oct 18.

European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.

Background: Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce.

Results: Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities.

Conclusions: Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.
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http://dx.doi.org/10.1186/1752-0509-6-133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605281PMC
October 2012

Software support for SBGN maps: SBGN-ML and LibSBGN.

Bioinformatics 2012 Aug 10;28(15):2016-21. Epub 2012 May 10.

EMBL European Bioinformatics Institute, Hinxton, UK.

Motivation: LibSBGN is a software library for reading, writing and manipulating Systems Biology Graphical Notation (SBGN) maps stored using the recently developed SBGN-ML file format. The library (available in C++ and Java) makes it easy for developers to add SBGN support to their tools, whereas the file format facilitates the exchange of maps between compatible software applications. The library also supports validation of maps, which simplifies the task of ensuring compliance with the detailed SBGN specifications. With this effort we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner.

Availability And Implementation: Milestone 2 was released in December 2011. Source code, example files and binaries are freely available under the terms of either the LGPL v2.1+ or Apache v2.0 open source licenses from http://libsbgn.sourceforge.net.

Contact: sbgn-libsbgn@lists.sourceforge.net.
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http://dx.doi.org/10.1093/bioinformatics/bts270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400951PMC
August 2012

PathVisio-Validator: a rule-based validation plugin for graphical pathway notations.

Bioinformatics 2012 Mar 22;28(6):889-90. Epub 2011 Dec 22.

Keshav Memorial Institute of Technology, Hyderabad, Andhra Pradesh, India.

Purpose: The PathVisio-Validator plugin aims to simplify the task of producing biological pathway diagrams that follow graphical standardized notations, such as Molecular Interaction Maps or the Systems Biology Graphical Notation. This plugin assists in the creation of pathway diagrams by ensuring correct usage of a notation, and thereby reducing ambiguity when diagrams are shared among biologists. Rulesets, needed in the validation process, can be generated for any graphical notation that a developer desires, using either Schematron or Groovy. The plugin also provides support for filtering validation results, validating on a subset of rules, and distinguishing errors and warnings.
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http://dx.doi.org/10.1093/bioinformatics/btr694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307104PMC
March 2012

WikiPathways: building research communities on biological pathways.

Nucleic Acids Res 2012 Jan 16;40(Database issue):D1301-7. Epub 2011 Nov 16.

Department of Bioinformatics-BiGCaT, Maastricht University, Maastricht, The Netherlands.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. 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 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. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. 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.
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http://dx.doi.org/10.1093/nar/gkr1074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245032PMC
January 2012

PathVisio-MIM: PathVisio plugin for creating and editing Molecular Interaction Maps (MIMs).

Bioinformatics 2011 Aug 2;27(15):2165-6. Epub 2011 Jun 2.

Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Motivation: A plugin for the Java-based PathVisio pathway editor has been developed to help users draw diagrams of bioregulatory networks according to the Molecular Interaction Map (MIM) notation. Together with the core PathVisio application, this plugin presents a simple to use and cross-platform application for the construction of complex MIM diagrams with the ability to annotate diagram elements with comments, literature references and links to external databases. This tool extends the capabilities of the PathVisio pathway editor by providing both MIM-specific glyphs and support for a MIM-specific markup language file format for exchange with other MIM-compatible tools and diagram validation.

Availability: The PathVisio-MIM plugin is freely available and works with versions of PathVisio 2.0.11 and later on Windows, Mac OS X and Linux. Information about MIM notation and the MIMML format is available at http://discover.nci.nih.gov/mim. The plugin, along with diagram examples, instructions and Java source code, may be downloaded at http://discover.nci.nih.gov/mim/mim_pathvisio.html.
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http://dx.doi.org/10.1093/bioinformatics/btr336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137219PMC
August 2011

Increasing soy isoflavonoid content and diversity by simultaneous malting and challenging by a fungus to modulate estrogenicity.

J Agric Food Chem 2011 Jun 31;59(12):6748-58. Epub 2011 May 31.

Laboratory of Food Chemistry, Wageningen University , P.O. Box 8129, 6700 EV Wageningen, The Netherlands.

Soybeans were germinated on a kilogram-scale, by the application of malting technology used in the brewing industry, and concomitantly challenged with Rhizopus microsporus var. oryzae. In a time-course experiment, samples were taken every 24 h for 10 days, and the isoflavonoid profile was analyzed by RP-UHPLC-MS. Upon induction with R. microsporus, the isoflavonoid composition changed drastically with the formation of phytoalexins belonging to the subclasses of the pterocarpans and coumestans and by prenylation of the various isoflavonoids. The pterocarpan content stabilized at 2.24 mg of daidzein equivalents (DE) per g after ∼9 days. The levels of the less common glyceofuran, glyceollin IV, and V/VI ranged from 0.18 to 0.35 mg DE/g and were comparable to those of the more commonly reported glyceollins I, II, and III (0.22-0.32 mg DE/g) and glycinol (0.42 mg DE/g). The content of prenylated isoflavones after the induction process was 0.30 mg DE/g. The total isoflavonoid content increased by a factor of 10-12 on DW basis after 9 days, which was suggested to be ascribable to de novo synthesis. These changes were accompanied by a gradual increase in agonistic activity of the extracts toward both the estrogen receptor α (ERα) and ERβ during the 10-day induction, with a more pronounced activity toward ERβ. Thus, the induction process yielded a completely different spectrum of isoflavonoids, with a much higher bioactivity toward the estrogen receptors. This, together with the over 10-fold increase in potential bioactives, offers promising perspectives for producing more, novel, and higher potency nutraceuticals by malting under stressed conditions.
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http://dx.doi.org/10.1021/jf2010707DOI Listing
June 2011

The BioPAX community standard for pathway data sharing.

Nat Biotechnol 2010 Sep 9;28(9):935-42. Epub 2010 Sep 9.

Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.
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http://dx.doi.org/10.1038/nbt.1666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001121PMC
September 2010

The BridgeDb framework: standardized access to gene, protein and metabolite identifier mapping services.

BMC Bioinformatics 2010 Jan 4;11. Epub 2010 Jan 4.

Department of Bioinformatics-BiGCaT, Maastricht University, Maastricht, the Netherlands.

Background: Many complementary solutions are available for the identifier mapping problem. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services.

Results: Here we present BridgeDb, a software framework for gene, protein and metabolite identifier mapping. This framework provides a standardized interface layer through which bioinformatics tools can be connected to different identifier mapping services. This approach makes it easier for tool developers to support identifier mapping. Mapping services can be combined or merged to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb provides its own ready-to-go mapping services, both in webservice and local database forms. However, the framework is intended for customization and adaptation to any identifier mapping service. BridgeDb has already been integrated into several bioinformatics applications.

Conclusion: By uncoupling bioinformatics tools from mapping services, BridgeDb improves capability and flexibility of those tools. All described software is open source and available at http://www.bridgedb.org.
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http://dx.doi.org/10.1186/1471-2105-11-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824678PMC
January 2010

Mining biological pathways using WikiPathways web services.

PLoS One 2009 Jul 30;4(7):e6447. Epub 2009 Jul 30.

Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands.

WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714472PMC
July 2009

Bioinformatics for the NuGO proof of principle study: analysis of gene expression in muscle of ApoE3*Leiden mice on a high-fat diet using PathVisio.

Genes Nutr 2008 Dec 26;3(3-4):185-91. Epub 2008 Nov 26.

Department of Bioinformatics-BiGCaT, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands,

Insulin resistance is a characteristic of type-2 diabetes and its development is associated with an increased fat consumption. Muscle is one of the tissues that becomes insulin resistant after high fat (HF) feeding. The aim of the present study is to identify processes involved in the development of HF-induced insulin resistance in muscle of ApOE3*Leiden mice by using microarrays. These mice are known to become insulin resistant on a HF diet. Differential gene expression was measured in muscle using the Affymetrix mouse plus 2.0 array. To get more insight in the processes, affected pathway analysis was performed with a new tool, PathVisio. PathVisio is a pathway editor customized with plug-ins (1) to visualize microarray data on pathways and (2) to perform statistical analysis to select pathways of interest. The present study demonstrated that with pathway analysis, using PathVisio, a large variety of processes can be investigated. The significantly regulated genes in muscle of ApOE3*Leiden mice after 12 weeks of HF feeding were involved in several biological pathways including fatty acid beta oxidation, fatty acid biosynthesis, insulin signaling, oxidative stress and inflammation.
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http://dx.doi.org/10.1007/s12263-008-0100-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593012PMC
December 2008

Presenting and exploring biological pathways with PathVisio.

BMC Bioinformatics 2008 Sep 25;9:399. Epub 2008 Sep 25.

Department of Bioinformatics, BiGCaT Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands.

Background: Biological pathways are a useful abstraction of biological concepts, and software tools to deal with pathway diagrams can help biological research. PathVisio is a new visualization tool for biological pathways that mimics the popular GenMAPP tool with a completely new Java implementation that allows better integration with other open source projects. The GenMAPP MAPP file format is replaced by GPML, a new XML file format that provides seamless exchange of graphical pathway information among multiple programs.

Results: PathVisio can be combined with other bioinformatics tools to open up three possible uses: visual compilation of biological knowledge, interpretation of high-throughput expression datasets, and computational augmentation of pathways with interaction information. PathVisio is open source software and available at http://www.pathvisio.org.

Conclusion: PathVisio is a graphical editor for biological pathways, with flexibility and ease of use as primary goals.
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http://dx.doi.org/10.1186/1471-2105-9-399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569944PMC
September 2008

Distinct gene expression profiles in adult rat brains after acute MK-801 and cocaine treatments.

Eur Neuropsychopharmacol 2006 Apr 20;16(3):211-9. Epub 2005 Oct 20.

Department of Neurobiology, A.I. Virtanen Institute, Kuopio 70211, Finland.

Uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists have been suggested to attenuate the self-administration and rewarding effects of psychostimulants. Microarrays containing 14,500 rat cDNAs were hybridized to identify alterations in gene expression levels in rat brain regions elicited by the uncompetitive NMDA receptor antagonist MK-801 (dizocilpine, 1 mg/kg), the dopamine agonist cocaine (20 mg/kg), or combined treatment (MK-801 15 min prior to cocaine) 4 h after injections. Total genes up regulated (Z-ratio >2) in parietal cortex and nucleus accumbens were 111 and 158, respectively. Total genes down regulated (Z-ratio <2) in the same tissues were 360 and 166, respectively. These genes fell into multiple molecular function gene ontology (GO) categories, but were highly represented in catalytic activities (44% of all genes), signal transduction (14%), protein (20%), nucleotide (18%), and nucleic acid (15%) binding. In nucleus accumbens, genes up regulated by MK-801 (87 genes) did not overlap those up regulated by cocaine (46 genes). Genes down regulated by MK-801 (33 genes) consisted of 2 overlapping genes with those down regulated by cocaine (89 genes). In parietal cortex, low numbers of overlapping regulated genes were also observed. Combined treatments also indicated low numbers (0-10) of genes commonly regulated when compared with single treatments alone. In situ hybridisation studies indicated significant increases in b-ZIP transcription factors (CREM, ICER, CBP, and c-fos) elicited by MK-801 and decreases in c-fos elicited by cocaine. The results indicate independent gene expression signatures following acute MK-801 and cocaine administration that appears to be largely non-overlapping and context dependent.
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http://dx.doi.org/10.1016/j.euroneuro.2005.08.007DOI Listing
April 2006