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Cited by 755Bioinformatics and Genomic NetworksBiomedical Text Mining and OntologiesScientific Computing and Data Management

The BioPAX community standard for pathway data sharing

Open access
Demir, Emek, Cary, Michael P, Paley, Suzanne, Fukuda, Ken, Lemer, Christian, Vastrik, Imre, Wu, Guanming, D'Eustachio, Peter +82 more·2010·Nature Biotechnology
DOI 10.1038/nbt.1666PMC PMC3001121
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

BioPAX is a community-developed OWL-based standard language for exchanging biological pathway data, covering metabolic and signaling pathways, molecular and genetic interactions, and gene regulation. It aims to reduce fragmentation across pathway databases and tools by making pathway data computable for visualization, analysis, and integration.

Key findings

  • BioPAX provides an ontology, OWL-based syntax, and a validator; it supports metabolic pathways, signaling pathways, gene regulatory networks, molecular interactions, and genetic interactions, with Level 3 currently recommended.
  • The paper reports that pathway and molecular interaction online resources grew from 190 in 2006 to 325 in 2010, a 70% increase, and that over 300 pathway or molecular interaction related data resources existed.
  • Through BioPAX, “millions of interactions organized into thousands of pathways across many organisms” are available in computable form from a growing number of sources.
  • BioPAX levels evolved incrementally: Level 1 supports metabolic pathways; Level 2 adds molecular interactions and post-translational modifications via PSI-MI; Level 3 adds signaling pathways, molecular state, gene regulation, and genetic interactions, but broke backwards compatibility.

Methods

  • Not an empirical study; the paper describes a community consensus process, including more than 15 BioPAX workshops since November 2002, mailing lists, a community wiki, and incremental language levels.
  • It describes ontology design, scope, validation, and coordination with related standards such as PSI-MI, SBGN, SBML, and CellML; no statistical analysis is reported.
  • Evidence comes from referenced pathway databases, software tools, and use cases rather than a formal sample or experimental dataset.

Limitations

  • The paper states that BioPAX does not support dynamic and quantitative aspects of biological processes, including temporal aspects of feedback loops and calcium waves; it coordinates with SBML and CellML for these.
  • The paper states that experimental evidence is included only for molecular interactions because PSI-MI already defined it; visualization is not standardized by BioPAX but coordinated with SBGN; semantic integration remains difficult due to multiple abstractions, different controlled vocabularies, data incompleteness, or errors; and Level 3 broke backwards compatibility.
  • Evident from the text: no empirical evaluation or benchmarking of adoption, interoperability, or user outcomes is reported; the paper is a descriptive community and standard report.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/nbt.1666

Cites

85 of 85 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingreasoning

    A range of BioPAX-aware software has been developed, including browsers, visualizers, querying engines, editors and converters.

    “Using Paxtools and other tools, a range of BioPAX-aware software has been developed, including browsers, visualizers, querying engines, editors and converters (Table 2).”
    Quote in the paperNot a substantial claim
  • Interpretationreasoning

    Researchers waste much time collecting information from different sources and converting its representation from one system to another.

    “As a result, researchers waste much time collecting information from different sources and converting its representation from one system to another.”
    Quote in the paperSubstantial claim
  • Interpretationreasoning

    BioPAX makes pathway data substantially easier to collect, index, interpret and share.

    “BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share.”
    Quote in the paperSubstantial claim
  • Interpretationcitation

    BioPAX can be used to aggregate large pathway datasets by reducing required collection and translation effort.

    “BioPAX can be used to help aggregate large pathway datasets by reducing the required collection and translation effort, for instance using software such as cPath43.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] 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). source

      Not checked in the free run.

  • Interpretationreasoning

    The growth of pathway data poses a formidable challenge for pathway data collection and curation and for database, visualization and analysis software because the data are often fragmented.

    “However, this growth poses a formidable challenge for pathway data collection and curation as well as for database, visualization and analysis software, as these data are often fragmented.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 47
  • May combine two claims. 17

  • Classified as probably not a substantial claim.

    Findingnone given

    Through BioPAX, millions of interactions organized into thousands of pathways across many organisms from a growing number of sources are available.

    “Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingnone given

    BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks.

    “BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks.”
    • Also stated in: § Implementation: the BioPAX biological pathway exchange language · plain
      “BioPAX supports representation of metabolic and signaling pathways, molecular and genetic interactions and gene regulation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX covers all major concepts familiar to biologists studying pathways, including metabolic and signaling pathways, gene regulatory networks and genetic and molecular interactions.

    “BioPAX covers all major concepts familiar to biologists studying pathways, including metabolic and signaling pathways, gene regulatory networks and genetic and molecular interactions (Table 3).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Reactome BioPAX formatted pathways are imported by the NCI/Nature Pathway Information Database (PID).

    “For example, Reactome8 BioPAX formatted pathways are imported by the NCI/Nature Pathway Information Database (PID)9.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Matthews, L. et al. Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 37, D619–D622 (2009). source

      Not checked in the free run.

    • cites [9] Schaefer, C.F. et al. PID: the Pathway Interaction Database. Nucleic Acids Res. 37, D674–D679 (2009). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    BioPAX has been used in a number of studies to collect and integrate large amounts of pathway information from multiple databases for analysis.

    “BioPAX has been used in a number of these studies to collect and integrate large amounts of pathway information from multiple databases for analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Many core BioPAX classes have remained compatible with previous levels since Level 1.

    “many core classes have remained compatible with previous levels since Level 1”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX Level 2 adds support for molecular interactions and post-translational protein modifications by integrating PSI-MI data structures.

    “Level 2 adds support for molecular interactions and post-translational protein modifications by integrating data structures from the PSI-MI format”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    In BioPAX, Molecular Weight must be a positive number.

    “Molecular Weight must be a positive number.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Broader input into BioPAX came from mailing lists and a community wiki.

    “Broader input came from mailing lists and a community wiki.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    PSI-MI to BioPAX and SBML to BioPAX converters are available.

    “For instance, PSI-MI to BioPAX and SBML to BioPAX converters are available (Table 2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Software is provided for updating older BioPAX pathways to Level 3 via Paxtools.

    “software is provided for updating older BioPAX pathways to Level 3 (via Paxtools).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    All BioPAX material is made freely available under open source licenses via a central website.

    “All BioPAX material (Table 1) is made freely available under open source licenses via a central website (http://www.biopax.org) in order to encourage broad adoption.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX Level 3 involved a major redesign that necessitated breaking backwards compatibility.

    “Level 3 involved a major redesign that necessitated breaking backwards compatibility.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX is compatible with semantic web technologies through use of the W3C standard Web Ontology Language, OWL.

    “BioPAX is compatible with them through use of the W3C standard Web Ontology Language, OWL.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    ChiBE and VisANT pathway visualization tools read BioPAX format.

    “For instance, the ChiBE and VisANT pathway visualization tools read BioPAX format22 and the WikiPathways website53, a community wiki for pathways, is working on using BioPAX to help import pathways from numerous sources, including manually edited pathways from biologists.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Hu, Z. et al. VisANT 3.0: new modules for pathway visualization, editing, prediction and construction. Nucleic Acids Res. 35, W625–W632 (2007). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX Level 1 supports metabolic pathways.

    “Level 1 supports metabolic pathways”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    WikiPathways is working on using BioPAX to import pathways from numerous sources.

    “For instance, the ChiBE and VisANT pathway visualization tools read BioPAX format22 and the WikiPathways website53, a community wiki for pathways, is working on using BioPAX to help import pathways from numerous sources, including manually edited pathways from biologists.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Pico, A.R. et al. WikiPathways: pathway editing for the people. PLoS Biol. 6, e184 (2008). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    In BioPAX, a Small Molecule is related to the Chemical Structure class by the property structure.

    “a Small Molecule is related to the Chemical Structure class by the property structure.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    BioPAX defines the classes, properties, and restrictions required to represent biological pathways and leaves creation of individuals to users.

    “BioPAX defines the classes, properties and restrictions required to represent biological pathways and leaves creation of the individuals to users (data providers and consumers).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Descriptions of millions of interactions in thousands of pathways across many organisms from multiple databases are now available in BioPAX format.

    “the descriptions of millions of interactions in thousands of pathways across many organisms from multiple databases are now available in BioPAX format.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BioPAX Level 2 is backwards compatible with Level 1.

    “Level 2 is backwards compatible with Level 1”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Cytoscape network visualization software can read and display BioPAX formatted data as a network.

    “For example, the Cytoscape network visualization software20 can read and display BioPAX formatted data as a network.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Community members participated in developing functionality they were interested in, which was integrated into specific levels.

    “Community members participated in developing functionality they were interested in, which was integrated into specific levels (See Supplementary Table S1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    Pathway Tools software and CellDesigner pathway editor are developing support for BioPAX-based data exchange.

    “The Pathway Tools software21 and CellDesigner pathway editor54 are developing support for BioPAX-based data exchange.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] 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). source

      Not checked in the free run.

    • cites [54] Kitano, H., Funahashi, A., Matsuoka, Y. & Oda, K. Using process diagrams for the graphical representation of biological networks. Nat. Biotechnol. 23, 961–966 (2005). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    More than 15 BioPAX workshops have been held since November 2002, with diverse participants.

    “More than 15 BioPAX workshops have been held since November 2002, attended by a diverse set of participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    BioPAX Level 3 adds support for signaling pathways, molecular state, gene regulation, and genetic interactions.

    “Level 3 adds support for signaling pathways, molecular state, gene regulation and genetic interactions (Table 3).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    In BioPAX, the Biochemical Reaction class is a subclass of the Conversion class.

    “in BioPAX, the Biochemical Reaction class is a ‘subclass of’ the Conversion class.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Incremental BioPAX versions were developed at workshops to focus on attainable intermediate goals.

    “Incremental versions (or levels) of the BioPAX language were progressively developed at these workshops to focus the group’s efforts on attainable intermediate goals.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    A common, inclusive and computable pathway data language is necessary to share knowledge about pathway maps and facilitate integration and use for hypothesis testing in biology.

    “A common, inclusive and computable pathway data language is necessary to share knowledge about pathway maps and to facilitate integration and use for hypothesis testing in biology24.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Racunas, S.A., Shah, N.H., Albert, I. & Fedoroff, N.V. HyBrow: a prototype system for computer-aided hypothesis evaluation. Bioinformatics 20 Suppl 1, i257–i264 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Over 300 pathway or molecular interaction related data resources and many visualization and analysis software tools have been developed.

    “Over 300 pathway or molecular interaction related data resources17 and many visualization and analysis software tools3,20-22 have been developed.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [17] Bader, G.D., Cary, M.P. & Sander, C. Pathguide: a pathway resource list. Nucleic Acids Res. 34, D504–D506 (2006). source

      Not checked in the free run.

    • cites [3] Demir, E. et al. PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways. Bioinformatics 18, 996–1003 (2002). source

      Not checked in the free run.

    • cites [20] Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003). source

      Not checked in the free run.

    • cites [21] 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). source

      Not checked in the free run.

    • cites [22] Hu, Z. et al. VisANT 3.0: new modules for pathway visualization, editing, prediction and construction. Nucleic Acids Res. 35, W625–W632 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Visualization and analysis tools developed for one pathway database cannot be reused for others, making software development efforts more expensive.

    “For instance, visualization and analysis tools developed for one pathway database cannot be reused for others, making software development efforts more expensive.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Most pathway databases and tools were originally developed with their own pathway representation language, resulting in a heterogeneous set of resources that are extremely difficult to combine and use.

    “Unfortunately, most of these databases and tools were originally developed to use their own pathway representation language, resulting in a heterogeneous set of resources that are extremely difficult to combine and use.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    A shared language facilitates communication by reducing the number of translations required to exchange data between multiple sources.

    “A shared language facilitates communication by reducing the number of translations required to exchange data between multiple sources (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    BioPAX reuses standard controlled vocabularies, including Gene Ontology for cellular location, PSI-MI vocabularies for evidence codes and interaction types, and Sequence Ontology for sequence regions.

    “BioPAX reuses a number of standard controlled vocabularies defined by other groups. For example, Gene Ontology40 is used to describe cellular location, PSI-MI vocabularies38 are used to define evidence codes, experimental forms, interaction types, relationship types and sequence modifications, and Sequence Ontology41 is used to define types of sequence regions, such as a promoter region on DNA in”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [40] Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25–29 (2000). source

      Not checked in the free run.

    • cites [38] Kerrien, S. et al. Broadening the horizon—level 2.5 of the HUPO-PSI format for molecular interactions. BMC Biol. 5, 44 (2007). source

      Not checked in the free run.

    • cites [41] Eilbeck, K. et al. The Sequence Ontology: a tool for the unification of genome annotations. Genome Biol. 6, R44 (2005). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    BioPAX is a standard language for representing biological pathways at the molecular and cellular levels.

    “BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Community coordination and agreement on one or a few standard sets of semantics is necessary to efficiently integrate pathway data from multiple sources on a large scale.

    “While independent research efforts are needed to find the best ways to represent pathways, community coordination and agreement on one or a few standard sets of semantics is necessary to be able to efficiently integrate pathway data from multiple sources on a large scale.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Molecular profiling methods provide large amounts of information about dynamics of cellular pathway components and increase power of pathway analysis techniques.

    “In addition, molecular profiling methods, such as RNA profiling using microarrays or protein quantification using mass spectrometry, provide large amounts of information about the dynamics of cellular pathway components and increase the power of pathway analysis techniques18,19.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Huang, W., Sherman, B.T. & Lempicki, R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1–13 (2009). source

      Not checked in the free run.

    • cites [19] Chuang, H.Y., Lee, E., Liu, Y.T., Lee, D. & Ideker, T. Network-based classification of breast cancer metastasis. Mol. Syst. Biol. 3, 140 (2007). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    BioPAX is implemented as an ontology.

    “It is implemented as an ontology, a formal system of describing knowledge (Box 1) that helps structure pathway data so that it is more easily processed by computer software (Figure 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Typical biological queries generate more complete answers when querying larger pathway datasets.

    “Typical biological queries, such as “What reactions involve my protein of interest?” generate more complete answers when querying these larger pathway datasets.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    BioPAX provides a validator that uses rules to verify whether a BioPAX document is complete, consistent and free of common errors.

    “Finally, it provides a validator that uses a set of rules to verify whether a BioPAX document is complete, consistent and free of common errors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A number of recent papers have used pathway analysis workflow to highlight genes and pathways active in specific model organisms or diseased tissues.

    “A number of recent papers have used this pathway analysis workflow to highlight genes and pathways that are active in specific model organisms or diseased tissues, such as breast cancer, using gene and protein expression, copy number variants (CNVs) and SNPs19,44-49.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [19] Chuang, H.Y., Lee, E., Liu, Y.T., Lee, D. & Ideker, T. Network-based classification of breast cancer metastasis. Mol. Syst. Biol. 3, 140 (2007). source

      Not checked in the free run.

    • cites [44] Cline, M.S. et al. Integration of biological networks and gene expression data using Cytoscape. Nat. Protoc. 2, 2366–2382 (2007). source

      Not checked in the free run.

    • cites [45] Efroni, S., Carmel, L., Schaefer, C.G. & Buetow, K.H. Superposition of transcriptional behaviors determines gene state. PLoS ONE 3, e2901 (2008). source

      Not checked in the free run.

    • cites [46] Ideker, T., Ozier, O., Schwikowski, B. & Siegel, A.F. Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 18 Suppl 1, S233–S240 (2002). source

      Not checked in the free run.

    • cites [47] Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008). source

      Not checked in the free run.

    • cites [48] Wu, G., Feng, X. & Stein, L. A human functional protein interaction network and its application to cancer data analysis. Genome Biol. 11, R53 (2010). source

      Not checked in the free run.

    • cites [49] Pinto, D. et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368–372 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Community workshops support a positive feedback cycle of knowledge sharing that has led to an accepted BioPAX language and development of better software and databases.

    “Thus, community workshops support a positive feedback cycle of knowledge sharing that has led to an accepted BioPAX language and development of better software and databases.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Solutions are discovered in independent research groups and incorporated in new data models and community best practices, which then enable identification of new issues.

    “Solutions are discovered in independent research groups and incorporated in new data models and community best practices, which then enable identification of new issues.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    BioPAX is developed through community consensus among data providers, tool developers, and pathway data users.

    “BioPAX is developed via community consensus among data providers, tool developers and pathway data users.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Community consensus is an effective way to develop a standard.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Linked, structured data form the basis of the semantic web, an extension of the WWW that promises improved information management and search capability.

    “Such linked, structured data form the basis of the semantic web, an extension of the WWW that promises improved information management and search capability61.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Berners-Lee, T. & Hendler, J. Publishing on the semantic web. Nature 410, 1023–1024 (2001). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The process of achieving community consensus spurs innovation in pathway informatics.

    “the process of achieving community consensus spurs innovation in the field of pathway informatics.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Advantages of implementing BioPAX using OWL include that both the ontology and the individuals and values can be stored in the same XML-based format, which makes data transmission easier.

    “Advantages of implementing BioPAX using OWL are that both the ontology and the individuals and values can be stored in the same XML-based format, which makes data transmission easier.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Representing and sharing knowledge using ontologies is simplified by the availability of OWL.
    • Rests on an assumption: OWL is a standard ontology language supported by useful software tools for editing, transmitting, querying, reasoning, and visualizing.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Community discussion helps resolve technical knowledge representation issues and facilitates convergence to common terminology and representation.

    “Community discussion helps resolve technical knowledge representation issues faced by many data providers and users and facilitates the convergence to common terminology and representation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    BioPAX does not support dynamic and quantitative aspects of biological processes, but coordinates with SBML and CellML mathematical modeling languages.

    “BioPAX does not support this, but coordinates with the SBML and CellML mathematical modeling languages55,56 and a growing software toolset supporting biological process simulation57 which cover these aspects.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [55] Lloyd, C.M., Halstead, M.D. & Nielsen, P.F. CellML: its future, present and past. Prog. Biophys. Mol. Biol. 85, 433–450 (2004). source

      Not checked in the free run.

    • cites [56] Hucka, M. et al. The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19, 524–531 (2003). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The database and tool support of a common language aids the creation, analysis, visualization, and interpretation of integrated pathway maps.

    “The database and tool support (Table 2) of a common language aids the creation, analysis, visualization and interpretation of integrated pathway maps.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Because Reactome data were available in BioPAX format and Cytoscape could already read BioPAX format, a new pathway visualization feature was easy to implement.

    “Because Reactome data were available in BioPAX format, and Cytoscape could already read BioPAX format, this new feature was easy to implement.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Tools to edit OWL, such as Protégé, have been developed by the Semantic Web community and adopted in the life sciences.

    “Tools to edit OWL, such as Protégé65, have been developed by the Semantic Web community and adopted in the life sciences.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Wheeler, D.L. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 35, D5–D12 (2007). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Protein expression data combined with pathway information highlighted the importance of apoptosis in a mouse model of heart disease.

    “For instance, protein expression data was combined with pathway information to highlight the importance of apoptosis in a mouse model of heart disease50.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Isserlin, R. et al. Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps. Proteomics 10, 1316–1327 (2010). source

      Not checked in the free run.

53 of 53

  • The paper relies on this without support.

    BioPAX is the only community standard for biological pathway exchange to and from databases.

    “BioPAX is the only community standard for biological pathway exchange to and from databases, but coordinates with other standards in related areas (Figure 6).”

  • The paper relies on this without support.

    Formal representation is required for computer software to make use of information.

    “Formal representation is required for computer software to make use of information.”

  • The paper relies on this without support.

    A formal representation allows consistent communication of knowledge between individuals or computer systems and helps manage complexity in information processing by breaking knowledge into clear concepts.

    “A formal representation allows for consistent communication of knowledge between individuals or computer systems and helps manage complexity in information processing as knowledge is broken down into clear concepts that can be considered independently.”

  • The paper relies on this without support.

    Ontologies enable integration of knowledge between independent resources linked on the WWW.

    “Ontologies also enable integration of knowledge between independent resources linked on the World Wide Web (WWW).”

  • The paper relies on this without support.

    Representing and sharing knowledge using ontologies is simplified by the availability of OWL.

    “Representing and sharing knowledge using ontologies is simplified by availability of the standard web ontology language (OWL) (http://www.w3.org/TR/owl-features/).”

  • The paper relies on this without support.

    OWL is a standard ontology language supported by useful software tools for editing, transmitting, querying, reasoning, and visualizing.

    “OWL is a standard ontology language that is supported by useful software tools for editing, transmitting, querying, reasoning and visualizing.”

  • The paper relies on this without support.

    Community consensus is an effective way to develop a standard.

    “BioPAX is developed via community consensus among data providers, tool developers and pathway data users.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Whereas SBML and CellML focus on quantitative modelling and dynamic simulation, BioPAX concentrates primarily on quantitative processes and visualization.

    “Whereas SBML and CellML focus on quantitative modelling and dynamic simulation, BioPAX concentrates primarily on quantitative processes and visualization [15, 30].”

    From Adapting modeling and simulation credibility standards to computational systems biology (2023) · cites this paper as [15]

    In “What is not covered?” (page not provided), the paper says BioPAX does not support dynamic and quantitative aspects of biological processes; SBML and CellML cover those aspects. It also says BioPAX does not aim to standardize pathway visualization. The claim gets the SBML/CellML distinction right but reverses BioPAX’s stated scope. (LLM, conf=0.92)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Systems biology model representation has become standardized using XML-based languages SBML, CellML, and BioPAX.

    “For this reason, systems biology model representation has become standardized using XML-based languages SBML [10, 13], CellML [14], and BioPAX [15].”

    From Adapting modeling and simulation credibility standards to computational systems biology (2023) · cites this paper as [15]

  • BioPAX is an ontology that describes the biological semantics of metabolic, signaling, molecular, gene-regulatory, and genetic interaction networks.

    “BioPAX (Biological Pathway Exchange) is an ontology, a formal systems of describing knowledge that structures biological pathway data making it more easily processed by computer software [15]. It describes the biological semantics of metabolic, signaling, molecular, gene-regulatory, and genetic interaction networks [15].”

    From Adapting modeling and simulation credibility standards to computational systems biology (2023) · cites this paper as [15]

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Related

Authors
Demir, E., Cary, M. P., Paley, S., Fukuda, K., Lemer, C., Vastrik, I., Wu, G., D'Eustachio, P., Schaefer, C., Luciano, J., Schacherer, F., Martinez-Flores, I., Hu, Z., Jimenez-Jacinto, V., Joshi-Tope, G., Kandasamy, K., Lopez-Fuentes, A. C., Mi, H., Pichler, E., Rodchenkov, I., Splendiani, A., Tkachev, S., Zucker, J., Gopinath, G., Rajasimha, H., Ramakrishnan, R., Shah, I., Syed, M., Anwar, N., Babur, Ö., Blinov, M., Brauner, E., Corwin, D., Donaldson, S., Gibbons, F., Goldberg, R., Hornbeck, P., Luna, A., Murray-Rust, P., Neumann, E., Ruebenacker, O., Samwald, M., van Iersel, M., Wimalaratne, S., Allen, K., Braun, B., Whirl-Carrillo, M., Cheung, K.-H., Dahlquist, K., Finney, A., Gillespie, M., Glass, E., Gong, L., Haw, R., Honig, M., Hubaut, O., Kane, D., Krupa, S., Kutmon, M., Leonard, J., Marks, D., Merberg, D., Petri, V., Pico, A., Ravenscroft, D., Ren, L., Shah, N., Sunshine, M., Tang, R., Whaley, R., Letovksy, S., Buetow, K. H., Rzhetsky, A., Schachter, V., Sobral, B. S., Dogrusoz, U., McWeeney, S., Aladjem, M., Birney, E., Collado-Vides, J., Goto, S., Hucka, M., Le Novère, N., Maltsev, N., Pandey, A., Thomas, P., Wingender, E., Karp, P. D., Sander, C., & Bader, G. D.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • SRI International (US)
  • National Institute of Advanced Industrial Science and Technology (JP)
  • Université Libre de Bruxelles (BE)
  • Ontario Institute for Cancer Research (CA)
  • National Institutes of Health (US)
  • Boston University (US)
  • Johns Hopkins University (US)
  • University of Toronto (CA)
  • Rothamsted Research (GB)
  • Cell Signaling Technology (United States) (US)
  • Broad Institute (US)
  • Center for Food Safety and Applied Nutrition (US)
  • Oregon Health & Science University (US)
  • Environmental Protection Agency (US)
  • Argonne National Laboratory (US)
  • UConn Health (US)
  • Harvard University (US)
  • National Institute of Standards and Technology (US)
  • University of Auckland (NZ)
  • Syngenta (United States) (US)
  • Yale University (US)
  • Loyola Marymount University (US)
  • St. John's University (US)
  • Stanford University (US)
  • Columbia University (US)
  • SRA International (United States) (US)
  • University of Ottawa (CA)
  • Vertex Pharmaceuticals (United States) (US)
  • Medical College of Wisconsin (US)
  • Cornell University (US)
  • Cold Spring Harbor Laboratory (US)
  • Takeda Oncology (United States) (US)
  • Virginia Tech (US)
  • European Bioinformatics Institute (GB)
  • Kyoto University Institute for Chemical Research (JP)
  • California Institute of Technology (US)
  • University of Göttingen (DE)
Corresponding author
Bader, Gary D
ORCID
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2010-09
Volume
28
Issue
9
Pages
935-942
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt.1666
PMC
PMC3001121
OpenAlex
W1969709265
Semantic Scholar
1876dd0e382dd215782af61d09157646fc8eb204
Cited by
745
References
84
Citations by year
2026: 27 · 2025: 13 · 2024: 32 · 2023: 35 · 2022: 41 · 2021: 46 · 2020: 44 · 2019: 43 · 2018: 45 · 2017: 35 · 2016: 57 · 2015: 74 · 2014: 49 · 2013: 78 · 2012: 62
FWCI
26.30
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
  • Rothamsted Repository (Rothamsted Repository) (submittedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion)
  • ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion)
Funders
  • U.S. Department of Energy (FG02-04ER63931, DE‐FG02‐)
  • Genome Canada
  • Ontario Genomics
  • Ontario Genomics Institute
  • National Institutes of Health (5r13gm076939-03)
  • Biotechnology and Biological Sciences Research Council (BB/F010516/1)
  • National Human Genome Research Institute (P41HG004118, U54HG004028)
  • National Cancer Institute (P30CA069533)
  • National Institute of General Medical Sciences (R13 GM076939, 1R13GM076939, R01GM071962, R01GM070923, U24GM077678)
  • National Institute of Allergy and Infectious Diseases (U54AI081680)
  • National Center for Research Resources (R01RR022971)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
  • Social Sciences › Decision Sciences › Information Systems and Management › Scientific Computing and Data Management
Keywords
BioPAX, data exchange standards, pathway databases, metabolic pathways, signaling pathways, molecular interactions, gene regulatory networks, data interoperability
MeSH terms
Programming Languages, Software, Signal Transduction, Computational Biology, Databases as Topic, Information Dissemination, Metabolic Networks and Pathways

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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