Supplementary Table S1. An example BioPAX file describing the phosphorylation and activation of CHK2 by ATM in human. Data was originally obtained from the Reactome database8.
Nature Biotechnology: doi:10.1038/nbt.1666 Nature Biotechnology: doi:10.1038/nbt.1666 >EQUAL
Nature Biotechnology: doi:10.1038/nbt.1666
Nature Biotechnology: doi:10.1038/nbt.1666
Nature Biotechnology: doi:10.1038/nbt.1666
Nature Biotechnology: doi:10.1038/nbt.1666 Supplementary Table S2. An example BioPAX file describing the two reactions involved in glucose metabolism in Escherichia coli. Data was originally obtained from the EcoCyc database14.
>MTKYALVGDVGGTNARLALCDIASGEISQAKTYSGLDYPSLEAVIRVYLEEHKVEVKDGCIAIACPITGDWVAMTNHTWAFSIAE MKKNLGFSHLEIINDFTAVSMAIPMLKKEHLIQFGGAEPVEGKPIAVYGAGTGLGVAHLVHVDKRWVSLPGEGGHVDFAPNSEEEA IILEILRAEIGHVSAERVLSGPGLVNLYRAIVKADNRLPENLKPKDITERALADSCTDCRRALSLFCVIMGRFGGNLALNLGTFGG VFIAGGIVPRFLEFFKASGFRAAFEDKGRFKEYVHDIPVYLIVHDNPGLLGSGAHLRQTLGHIL
Nature Biotechnology: doi:10.1038/nbt.1666 >[CH]3(n1(c2(c(nc1)c(N)ncn2)))(O[CH]([CH](O)[CH](O)3)COP(=O)(O)OP(O)(=O)OP(O)(=O)O)
Nature Biotechnology: doi:10.1038/nbt.1666 Nature Biotechnology: doi:10.1038/nbt.1666 >SMILES
Nature Biotechnology: doi:10.1038/nbt.1666 >c12(n(cnc(c(N)ncn1)2)[CH]3(O[CH]([CH](O)[CH](O)3)COP(=O)(O)OP(O)(=O)O))
Nature Biotechnology: doi:10.1038/nbt.1666 >KTFSEAIISGEWKGYTGKAITDVVNIGIGGSDLGPYMVTEALRPYKNHLNMHFVSNVDGTHIAEVLKKVNPETTLFLVASKTFTT QETMTNAHSARDWFLKAAGDEKHVAKHFAALSTNAKAVGEFGIDTANMFEFWDWVGGRYSLWSAIGLSIVLSIGFDNFVELLSGAH AMDKHFSTTPAEKNLPVLLALIGIWYNNFFGAETEAILPYDQYMHRFAAYFQQGNMESNGKYVDRNGNVVDYQTGPIIWGEPGTNG QHAFYQLIHQGTKMVPCDFIAPAITHNPLFDHHQKLLSKFFAQTEALAFGKSREVVEQEYRDQGKDPAT
Nature Biotechnology: doi:10.1038/nbt.1666
Nature Biotechnology: doi:10.1038/nbt.1666 Nature Biotechnology: doi:10.1038/nbt.1666 >Glycolysis Pathway
Nature Biotechnology: doi:10.1038/nbt.1666
Supplementary Table S3: BioPAX covers five main types of biological pathways and coverage has increased over time with new levels of the ontology.
Type of Main BioPAX Classes Used Introduced Biological Pathway Metabolic All types of physical entities (most common use of protein, Level 1 pathways small molecule, complex), All types of conversion events (most common use of BiochemicalReaction, ComplexAssembly and Transport), Catalysis, Modulation and Pathway Signaling All types of physical entities (most common use of protein, Level 2 pathways complex), All types of conversion events (most common use of BiochemicalReaction, ComplexAssembly, Transport and Degradation), Control, Catalysis, Modulation, MolecularInteraction, Pathway Molecular All types of physical entities (most common use of protein, Level 2 interactions complex, small molecule), MolecularInteraction, Pathway Gene All types of physical entities, TemplateReaction, Level 3 regulatory TemplateReactionRegulation networks Genetic Gene, GeneticInteraction Level 3 interactions
Nature Biotechnology: doi:10.1038/nbt.1666 Supplementary Table S4: Databases and software supporting BioPAX. Note, PSI- MI data sources can be converted to BioPAX Level 2 using the PSI-MI to BioPAX converter.
Database Type URL Format License Statistics BIND 1 Protein http://tap.med.utoron PSI-MI Free to >85,000 interactions interactions to.ca/~bind/ Level 1 all BioCyc Metabolic and http://biocyc.org BioPAX Free to ~500 mostly databases signaling Level 3 all computationally predicted 2,3 pathway databases BioGRID 4,5 Protein- http://www.thebiogri PSI-MI Free to >265,000 interactions protein and d.org/ Level 1 all genetic and 2.5 interactions BioModels 6 Metabolic and http://biomodels.net/ SBML, Free to >450 pathways, >240 signaling BioPAX all curated pathways, Level 2 >40,000 interactions Cancer Cell Signaling http://cancer.cellmap BioPAX Free to Pathways: 10 Map Pathways .org Level 2 all Interactions: 2,104 Physical Entities: 899
DIP 7,8 Protein- http://dip.doe- PSI-MI Free for >57,000 interactions protein mbi.ucla.edu/ Level 1 Academi interactions cs Ecocyc 9 Metabolic and http://ecocyc.org/ BioPAX, Free to Pathways: 246 Signaling Level 3 all Regulatory interactions: Pathways 5,000 Metabolic reactions: 1400 Physical Entities: 3,606
HPRD 10 Protein- http://hprd.org/ PSI-MI Free for >38,000 interactions protein Level Academi interactions 2.5 cs IMID Signaling http://www.sbcny.org BioPAX Free to >2000 interactions /data.htm Level 2 all INOH Signaling http://www.inoh.org/ BioPAX Free to >60 pathways Level 2 all IntAct 11 Protein- http://www.ebi.ac.uk/ PSI-MI Free to >200,000 interactions protein intact Level 1 all interactions and 2.5 KEGG Metabolic http://www.genome.j BioPAX Free for >330 reference pathways Pathway 12 p/kegg/ Level 1 Academi cs MetaCyc 13 Metabolic and http://metacyc.org/ BioPAX Free to 1399 curated pathways, signaling Level 3 all >8,100 reactions MINT 14 Protein- http://mint.bio.uniro PSI-MI Free to >80,000 interactions protein ma2.it/mint Level 1 all interactions and 2.5 MIPS Protein- http://mips.gsf.de/ge PSI-MI Free to >12,000 interactions MPact 15 protein nre/proj/mpact/ Level 1 all interactions and 2.5 NCI/Nature Signaling http://pid.nci.nih.gov/ BioPAX Free to >400 curated pathways Pathway Level 2 all >12800 interactions
Nature Biotechnology: doi:10.1038/nbt.1666 Interaction Database 16 NetPath 17 Signaling http://netpath.org/ BioPAX Free to 20 large curated pathways Level 2 all OPHID 18 Protein- http://ophid.utoronto. PSI-MI Free for >424,000 interactions protein ca Level 1 Academi interaction cs Pathway Pathways and http://www.pathwayc BioPAX Free to >1,400 collected pathways Commons interactions ommons.org Level 2 all >421,000 interactions Reactome Metabolic and http://reactome.org/ BioPAX, Free to >50 curated pathways 19 Signaling Level 2 all Pathways RegulonDB Regulatory http://regulondb.ccg. BioPAX Free to Regulatory interactions: 20 Network unam.mx Level 3 all 2,594 Physical Entities: 18,371 Pathways: 2,660 Rhea Metabolic http://www.ebi.ac.uk/ BioPAX, Free to >11,000 reactions Reactions rhea Level 2 all Software Type URL Format License Language BiNoM 21 Editor/Convert http://bioinfo- BioPAX Free to Java er out.curie.fr/projects/ Level 1 all (open binom/ and 2 source) BioPAX Validator http://www.ohsucanc BioPAX Free to Java validator er.com/biopaxvalidat Level 1 all (open or/index.html and 2 source) BioPAX Validator http://www.biopax.or BioPAX Free to Java validator g/biopax-validator/ Level 3 all (open source) BioUML Editor/Simulat http://www.biouml.or BioPAX Free to Java or g/ Level 2 all (open source) Biowarehou Biological data http://biowarehouse. BioPAX Free to C and Java se warehouse ai.sri.com/ Level 1 all (open software and 2 source) ChiBE 79 Visualization http://www.bilkent.ed BioPAX Free for Java and analysis u.tr/~bcbi/chibe.html Level 1 Academi and 2 cs cPath 22 Pathway http://cbio.mskcc.org BioPAX Free to Java database /dev_site/cpath/ Level 1 all (open software and 2 source) Cytoscape Visualization http://cytoscape.org BioPAX Free to Java 23 and analysis Level 1, all (open 2, 3 source) ExPlain Pathway http://www.biobase- BioPAX Commerc Analysis analysis international.com/pa Level 1 ial System ges/index.php?id=28 and 2 6 GeneSpring Pathway http://www.agilent.co BioPAX Commerc Java GX analysis m/chem/genespring Level 1 ial and 2 Navigator 24 Visualization http://ophid.utoronto. BioPAX Free for Java and analysis ca/navigator/ Level 1 Academi and 2 cs Pathway Pathway http://bioinformatics. BioPAX Free for Lisp Tools 25 prediction, ai.sri.com/ptools/ Level 3 Academi
Nature Biotechnology: doi:10.1038/nbt.1666 editing, cs visualization, network analysis, gene expression analysis PATIKA 26 Visualization http://web.patika.org BioPAX Free for Java and analysis Level 1 Academi and 2 cs Paxtools BioPAX http://www.biopax.or BioPAX Free to Java input/export g/paxtools/ Level all (open library 1,2,3 source) PSI-MI to BioPAX BioPAX Free to Java BioPAX translator Level all (open converter 2,3 source) QPACA 27 Gene https://cabig.nci.nih. BioPAX Free to Java expression gov/tools/QPACA Level 1 all analysis and 2 SBML tp BioPAX http://www.ebi.ac.uk/ BioPAX Free to Java BioPAX translator compneur- Level 2 all (open converter srv/sbml/convertors/ source) SBMLtoBioPax.html SHARKvie Pathway http://www.bioinform BioPAX Free to Java w 28 visualizer atics.leeds.ac.uk/sha Level 1 all rk/ and 2 The Pathway http://jlab.calumet.pu BioPAX Free to Java Gateway to query web rdue.edu/theGatewa Level 1 all Biological service y/ and 2 Pathways VisANT 29,30 Visualization http://visant.bu.edu/ BioPAX Free to Java and analysis Level 1 all and 2
Nature Biotechnology: doi:10.1038/nbt.1666 Supplementary Table S5 - Author Contributions Developed BioPAX: Author Name Email Affiliation Level 1 Level 2 Level 3 Data provider Computational Biology, Memorial Sloan-Kettering Cancer Center, Emek Demir [email protected] New York, NY 10065 1 1 1 1 Computational Biology, Memorial Sloan-Kettering Cancer Center, Michael P. Cary [email protected] New York, NY 10065 1 1 1 1 SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025, Suzanne Paley [email protected] USA. 1 1 1 1 Institute for Bioinformatics Research and Development Japan Ken Fukuda [email protected] Science and Technology Agency Tokyo Japan. 1 1 1 1 Université libre de Bruxelles, boulevard du Triomphe CP 263, B- Christian Lemer [email protected] 1050 Bruxelles, Belgium 0 1 1 1 European Bioinformatics Institute, Wellcome Trust Genome Imre Vastrik [email protected] Campus, Hinxton, Cambridge CB10 1SD, UK 0 1 1 1 Ontario Institute for Cancer Research, Toronto, ON, Canada Guanming Wu [email protected] M5G0A3 0 1 1 1 Peter D'Eustachio Peter.D'[email protected] NYU School of Medicine, New York, NY 10016, USA 0 1 1 1 National Cancer Institute, Center for Biomedical Informatics and Carl F Schaefer [email protected] Information Technology, Rockville MD, USA 0 0 1 1 Frank Schacherer [email protected] BIOBASE Corporation 0 1 1 1 Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Irma Martinez-Flores [email protected] Cuernavaca, Morelos, Mexico. 0 0 1 1 Biomolecular Systems Laboratory, Boston University, Boston, MA, Zhenjun Hu [email protected] USA. 0 0 1 0 Programa de Genómica Computacional, Centro de Ciencias Veronica Jimenez- Genómicas, Universidad Nacional Autónoma de México, Jacinto [email protected] Cuernavaca, Morelos, Mexico 0 0 1 1 Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, Geeta Joshi-Tope [email protected] NY 11724 0 1 1 1 McKusick-Nathans Institute of Genetic Medicine and the Departments of Biological Chemistry, Pathology and Oncology, Kumaran Kandasamy [email protected] Johns Hopkins University, Baltimore, MD 21205, USA 0 0 1 1 Programa de Genómica Computacional, Centro de Ciencias Alejandra C. Lopez- Genómicas, Universidad Nacional Autónoma de México, Fuentes [email protected] Cuernavaca, Morelos, Mexico 0 0 1 1 Joanne Luciano [email protected] Predictive Medicine, Belmont, Massachusetts 02478, USA 1 1 1 0 Evolutionary Systems Biology Group, Artificial Intelligence Center, Huaiyu Mi [email protected] SRI International, Menlo Park, CA 94025, USA 0 0 1 1 Elgar Pichler [email protected] 0 1 1 0 Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Igor Rodchenkov [email protected] Toronto, Ontario, Canada 0 0 1 0 UPRES-EA 3888-Laboratoire d'Informatique Médicale, Faculté de Andrea Splendiani [email protected] Médecine, Université Rennes 1, Rennes FR-35043, France. 0 1 1 0 Sasha Tkachev [email protected] Cell Signaling Technology, Inc. Danvers, MA, USA. 0 0 1 1 Jeremy Zucker [email protected] Broad Institute 1 1 1 0 Center for Food Safety and Applied Nutrition, US Food and Drug Gopal Gopinath [email protected] Adminsitration, 8301 Muirkirk Road, Laurel, Maryland, 20708. USA 0 0 1 1 Virginia Bioinformatics Institute, Virginia Polytechnic Institute and Harsha Rajasimha [email protected] State University, Blacksburg, VA 24061, USA. 0 1 1 0 Division of Neuroscience. Oregon Health & Science University, Ranjani Ramakrishnan [email protected] Portland, OR 97239-3098, USA 0 0 1 0 Imran Shah [email protected] U.S. Environmental Protection Agency Durham, NC USA. 1 0 0 0 Mathematics & Computer Science Division, Argonne National Mustafa Syed [email protected] Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA 1 0 0 1 Computational Biology, Memorial Sloan-Kettering Cancer Center, Nadia Anwar [email protected] New York, NY 10065 0 0 1 0 Computational Biology, Memorial Sloan-Kettering Cancer Center, Ozgun Babur [email protected] New York, NY 10065 0 0 1 0 Michael Blinov [email protected] University of Connecticut Health Center, Farmington, CT, USA. 0 0 1 0
Nature Biotechnology: doi:10.1038/nbt.1666 Supplementary Table S5 - Author Contributions Developed BioPAX: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, SGMB-322, Erik Brauner [email protected] Boston, Massachusetts 02115 1 0 0 0 Dan Corwin [email protected] Lexikos Corporation, USA 0 1 1 0 Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Sylva Donaldson [email protected] Toronto, Ontario, Canada 0 0 1 0 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Longwood Avenue, Boston, Massachusetts Frank Gibbons [email protected] 02115, USA 0 1 0 0 Biotechnology Division, National Institute of Standards and Robert Goldberg [email protected] Technology, Gaithersburg, MD 20899, USA. 1 0 0 0 Cell Signaling Technology, 3 Trask Lane, Danvers, Massachusetts Peter Hornbeck [email protected] 01923, USA 0 0 1 1 National Cancer Institute, National Institute of Health, Washington Augustin Luna [email protected] DC USA. 0 0 1 0 Unilever Centre for Molecular Sciences Informatics, Department of Peter Murray-Rust [email protected] Chemistry, University of Cambridge, Cambridge CB2 1EW, UK 1 0 0 0 Eric Neumann [email protected] Clinical Semantics Group, Lexington, MA 02420, USA 1 1 0 0 Center for Cell Analysis and Modeling, University of Connecticut Oliver Reubenacker [email protected] Health Center, Storrs, CT, USA. 0 0 1 0 Digital Enterprise Research Institute, National University of Ireland, Galway, Ireland // Konrad Lorenz Institute for Evolution and Matthias Samwald [email protected] Cognition Research, Altenberg, Austria 0 0 1 0 Martijn van Iersel [email protected] University Maastricht 0 0 1 1 Sarala Wimalaratne [email protected] University of Auckland 0 0 1 0 Keith Allen [email protected] Syngenta Biotech Inc., Research Triangle Park, North Carolina, USA. 0 0 1 0 Burk Braun [email protected] BIOBASE Corporation 0 0 1 0 Yale Center for Medical Informatics, Yale University, New Haven, CT Kei-Hoi Cheung [email protected] USA 06511, USA 0 0 1 0 PharmGKB, Department of Genetics, Stanford University, Stanford, Michelle Whirl-Carrillo [email protected] California 94305-5120, USA. 0 0 1 0 Loyola Marymount University, 1 LMU Drive, MS 8220, Los Angeles, Kam Dahlquist [email protected] CA 90045-2659 0 1 0 0 Physiomics PLC, Magdalen Centre, Oxford Science Park, Oxford, Andrew Finney [email protected] OX4 4GA, UK 1 0 0 0 Marc Gillespie [email protected] St. John's University, Queens NY 11439 USA 0 0 1 0 Mathematics & Computer Science Division, Argonne National Elizabeth Glass [email protected] Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA 1 0 0 0 Department of Genetics, Stanford University, Stanford, California Li Gong [email protected] 94305-5120, USA. 0 0 1 0 Robin Haw [email protected] The Ontario Institute for Cancer Research 0 0 1 1 Michael Honig [email protected] Columbia University 0 0 1 0 Université libre de Bruxelles, boulevard du Triomphe CP 263, B- Olivier Hubaut [email protected] 1050 Bruxelles, Belgium 0 0 1 0 David Kane [email protected] SRA International, USA 0 1 0 0 Shiva Krupa [email protected] Novartis Knowledge Center, Cambridge MA, USA 0 0 1 0 Martina Kutmon [email protected] University of Ottawa 0 0 1 0 Julie Leonard [email protected] Syngenta Biotech Inc., Research Triangle Park, North Carolina, USA. 0 0 0 0 Department of Systems Biology, Harvard Medical School, Boston, Debbie Marks [email protected] MA, USA 1 0 0 0 David Merberg [email protected] Vertex Pharmaceuticals 130 Waverly Street Cambridge, MA 02139 0 0 1 0 Human and Molecular Genetics Center, Medical College of Victoria Petri [email protected] Wisconsin, Milwaukee, WI, USA 0 0 1 0 Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, Alex Pico [email protected] San Francisco, CA 94158, USA 0 0 1 1 Department of Plant Breeding and Genetics, 240 Emerson Hall, Dean Ravenscroft [email protected] Cornell University, Ithaca, NY 14853, USA 0 0 1 0 Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, Liya Ren [email protected] NY 11724 0 0 1 0
Nature Biotechnology: doi:10.1038/nbt.1666 Supplementary Table S5 - Author Contributions Developed BioPAX: Centre for Biomedical Informatics, School of Medicine, Stanford Nigam Shah [email protected] University, Stanford, CA 94305, USA 0 0 1 0 National Cancer Institute, National Institute of Health, Washington Margot Sunshine [email protected] DC USA. 0 0 1 1 Department of Genetics, Stanford University Medical Center, Rebecca Tang [email protected] Stanford, CA, USA. 0 0 1 1 Department of Genetics, Stanford University, Stanford, California Ryan Whaley [email protected] 94305-5120, USA. 0 0 1 0 Computational Sciences, Informatics, Millennium Pharmaceuticals Stan Letovksy [email protected] Inc., Cambridge, Massachusetts 02139, USA 1 0 0 0 Center for Biomedical Informatics and Information Technology, Neuro-Oncology Branch, National Cancer Institute, Bethesda, MD Kenneth H. Buetow [email protected] 20892, USA. 0 0 1 1 Institute for Genomics and Systems Biology, The University of Andrey Rzhetsky [email protected] Chicago and Argonne National Laboratory, Chicago, IL 60637, USA 1 1 0 0 Vincent Schachter [email protected] Total Gas & Power 1 0 0 0 Virginia Bioinformatics Institute at Virginia Tech, Blacksburg, VA, Bruno S. Sobral [email protected] USA 0 1 1 0 Center for Bioinformatics and Computer Engineering Department, Ugur Dogrusoz [email protected] Bilkent University, Ankara, Turkey 1 1 0 1 Department of Behavioral Neuroscience. Oregon Health & Science Shannon McWeeney [email protected] University, Portland, OR 97239-3098, USA 0 0 1 1 Laboratory of Molecular Pharmacology, Center for Cancer Mirit Aladjem [email protected] Research, NCI, NIH, Bethesda, MD 20892-4255, USA. 0 1 1 0 European Bioinformatics Institute, Wellcome Trust Genome Ewan Birney [email protected] Campus, Hinxton, Cambridge CB10 1SD, UK 0 1 1 1 Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Julio Collado-Vides [email protected] Cuernavaca, Morelos, Mexico 0 0 1 1 Bioinformatics Center, Institute for Chemical Research, Kyoto Susumu Goto [email protected] University, Uji, Kyoto 611-0011, Japan 1 0 0 1 Biological Network Modeling Center, California Institute of Michael Hucka [email protected] Technology, Pasadena, CA, USA. 1 1 1 0 European Bioinformatics Institute, Wellcome Trust Genome Nicolas Le Novère [email protected] Campus, Hinxton, Cambridge CB10 1SD, UK 0 0 1 1 Mathematics & Computer Science Division, Argonne National Natalia Maltsev [email protected] Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA 1 0 0 1 McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733N Broadway, Broadway Research Building 560, Baltimore, MD 21205, United States, Department of Oncology and Pathology, Johns Hopkins University School of Medicine, 733N Broadway, Akhilesh Pandey [email protected] Broadway 0 0 0 1 Evolutionary Systems Biology Group, Artificial Intelligence Center, Paul Thomas [email protected] SRI International, Menlo Park, CA 94025, USA 0 0 1 1 [email protected]. Department of Bioinformatics, Goldschmidtstr. 1, D-37077 Edgar Wingender de Göttingen, Germany. 0 1 1 1 SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025, Peter D. Karp [email protected] USA. 1 1 1 1 Computational Biology Center, Memorial Sloan-Kettering Cancer Chris Sander [email protected] Center, New York, NY 10065 1 1 1 1 Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Gary D. Bader [email protected] Toronto, Ontario, Canada 1 1 1 1
Nature Biotechnology: doi:10.1038/nbt.1666 References 1 Bader, G. D., Betel, D. & Hogue, C. W. BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248-250, (2003). 2 Karp, P. D. et al. Expansion of the BioCyc collection of pathway/genome databases to 160 genomes. Nucleic Acids Res 33, 6083-6089, (2005). 3 Romero, P. et al. Computational prediction of human metabolic pathways from the complete human genome. Genome Biol 6, R2, (2005). 4 Breitkreutz, B. J., Stark, C. & Tyers, M. The GRID: the General Repository for Interaction Datasets. Genome Biol. 4, R23, (2003). 5 Stark, C. et al. BioGRID: a general repository for interaction datasets. Nucleic Acids Res 34, D535-539, (2006). 6 Le Novere, N. et al. BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucleic Acids Res 34, D689-691, (2006). 7 Xenarios, I. et al. DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res. 30, 303- 305, (2002). 8 Salwinski, L. et al. The Database of Interacting Proteins: 2004 update. Nucleic Acids Res 32, D449-451, (2004). 9 Keseler, I. M. et al. EcoCyc: a comprehensive view of Escherichia coli biology. Nucleic Acids Res 37, D464-470, (2009). 10 Peri, S. et al. Development of Human Protein Reference Database as an initial platform for approaching systems biology in humans. Genome Res 13, 2363- 2371, (2003). 11 Hermjakob, H. et al. IntAct: an open source molecular interaction database. Nucleic Acids Res 32, D452-455, (2004). 12 Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y. & Hattori, M. The KEGG resource for deciphering the genome. Nucleic Acids Res 32 Database issue, D277-280, (2004). 13 Caspi, R. et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 38, D473-479, (2010). 14 Zanzoni, A. et al. MINT: a Molecular INTeraction database. FEBS Lett. 513, 135-140, (2002). 15 Guldener, U. et al. MPact: the MIPS protein interaction resource on yeast. Nucleic Acids Res 34, D436-441, (2006). 16 Schaefer, C. F. et al. PID: the Pathway Interaction Database. Nucleic Acids Res 37, D674-679, (2009). 17 Kandasamy, K. et al. NetPath: a public resource of curated signal transduction pathways. Genome Biol 11, R3, (2010). 18 Brown, K. R. & Jurisica, I. Online predicted human interaction database. Bioinformatics 21, 2076-2082, (2005). 19 Joshi-Tope, G. et al. Reactome: a knowledgebase of biological pathways. Nucleic Acids Res 33, D428-432, (2005).
Nature Biotechnology: doi:10.1038/nbt.1666 20 Gama-Castro, S. et al. RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation. Nucleic Acids Res 36, D120-124, (2008). 21 Zinovyev, A., Viara, E., Calzone, L. & Barillot, E. BiNoM: a Cytoscape plugin for manipulating and analyzing biological networks. Bioinformatics 24, 876-877, (2008). 22 Babur, O., Dogrusoz, U., Demir, E. & Sander, C. ChiBE: interactive visualization and manipulation of BioPAX pathway models. Bioinformatics 26, 429-431, (2010). 23 Cerami, E. G., Bader, G. D., Gross, B. E. & Sander, C. cPath: open source software for collecting, storing, and querying biological pathways. BMC Bioinformatics 7, 497, (2006). 24 Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13, 2498-2504, (2003). 25 Brown, K. R. et al. NAViGaTOR: Network Analysis, Visualization and Graphing Toronto. Bioinformatics 25, 3327-3329, (2009). 26 Karp, P. D. et al. Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology. Brief Bioinform 11, 40-79, (2010). 27 Demir, E. et al. PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways. Bioinformatics. 18, 996-1003, (2002). 28 Novak, B. A. & Jain, A. N. Pathway recognition and augmentation by computational analysis of microarray expression data. Bioinformatics 22, 233- 241, (2006). 29 Pinney, J. W., Shirley, M. W., McConkey, G. A. & Westhead, D. R. metaSHARK: software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella. Nucleic Acids Res 33, 1399-1409, (2005). 30 Hu, Z. et al. VisANT 3.0: new modules for pathway visualization, editing, prediction and construction. Nucleic Acids Res 35, W625-632, (2007). 31 Hu, Z., Mellor, J., Wu, J. & DeLisi, C. VisANT: an online visualization and analysis tool for biological interaction data. BMC Bioinformatics 5, 17, (2004).
Nature Biotechnology: doi:10.1038/nbt.1666 UtilityClass Evidence Stoichiometry Score ChemicalStructure ExperimentalForm DeltaG Xref Provenance KPrime PublicationXref BioSource RelationshipXref PathwayStep
EntityReference UnificationXref BiochemicalPathwayStep DnaReference
EntityFeature RnaReference
SequenceLocation ProteinReference FragmentFeature SmallMoleculeReference ModifcationFeature DnaRegionReference BindingFeature SequenceInterval RnaRegionReference
SequenceSite
CovalentBindingFeature ControlledVocabulary
CellularLocationVocabulary PhenotypeVocabulary
EvidenceCodeVocabulary RelationshipTypeVocabulary
CellVocabulary SequenceModificationVocabulary
EntityReferenceTypeVocabulary SequenceRegionVocabulary
ExperimentalFormVocabulary TissueVocabulary
InteractionVocabulary
Supplemental Figure S1. Diagram of BioPAX Level 3 utility classes. Nature Biotechnology: doi:10.1038/nbt.1666