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Bio onttalk 30minutes-june2003[1]


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Early talk on BioPAX at Bio-Ontologies

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Bio onttalk 30minutes-june2003[1]

  1. 1. BioPAX A Data Exchange Format for Biological Pathways BioPAX Workgroup
  2. 2. Introduction <ul><li>BioPAX = Biopathways Exchange Language </li></ul><ul><li>A data exchange format intended to facilitate sharing of pathway data </li></ul><ul><li>BioPAX will provide a consistent format for pathway data so it will be easier for consumers of pathway data (e.g. tool developers, DB curators) to integrate data from multiple sources. </li></ul>
  3. 3. Exchange Formats in the Pathway Data Space BioPAX Molecular Interactions Pro:Pro All:All PSI Biochemical Reactions SBML, CellML Regulatory Pathways Low Detail High Detail Genetic Interactions Interaction Networks Molecular Non-molecular Pro:Pro TF:Gene Genetic Metabolic Pathways Low Detail High Detail Database Exchange Formats Simulation Model Exchange Formats Small Molecules (CML) Rate Formulas
  4. 4. High Throughput Experimental Methods Expression, Interaction Data, Function, Protein modifications PubMed Existing Literature Multiple Pathway Databases Integration Nightmare! Microarray Two-Hybrid Mass Spectrometry Genetics
  5. 5. Goals <ul><li>Accommodate representations used in existing databases such as BioCyc, BIND, WIT, aMAZE, KEGG, etc. </li></ul><ul><li>Include support for these pathway types: </li></ul><ul><ul><li>Metabolic pathways </li></ul></ul><ul><ul><li>Signaling pathways </li></ul></ul><ul><ul><li>Protein-protein interactions </li></ul></ul><ul><ul><li>Genetic regulatory pathways </li></ul></ul>
  6. 6. Goals <ul><li>Extensible : Specific classes of data in BioPAX have been marked as extensible to allow addition of new types of data in the future </li></ul><ul><li>Encapsulation : An entire pathway can be encapsulated in a single BioPAX record </li></ul><ul><li>Compatible : BioPAX will try to use existing standards for encoding biological pathway related information wherever possible </li></ul><ul><li>Flexible : Different preferred representations of pathway data can be described using BioPAX </li></ul>
  7. 7. Ontology Syntax <ul><li>Ontology and data exchange format (DEF) are not identical </li></ul><ul><li>Ontology is implemented as the DEF </li></ul><ul><li>Multiple implementations are possible… </li></ul><ul><ul><li>Multiple syntax languages to choose from </li></ul></ul><ul><ul><li>Multiple ways to organize the data within each syntax </li></ul></ul>
  8. 8. Syntax Languages <ul><li>Currently translating BioPAX ontology into: </li></ul><ul><ul><li>An XML Schema </li></ul></ul><ul><ul><ul><li>Widely used syntax language </li></ul></ul></ul><ul><ul><li>An OWL Ontology </li></ul></ul><ul><ul><ul><li>More powerful data representation abilities </li></ul></ul></ul><ul><ul><ul><li>Community appears to be moving toward OWL (e.g. GO) </li></ul></ul></ul><ul><li>Both are XML-based </li></ul><ul><li>Both versions will be compatible with and fully translatable to each other </li></ul><ul><li>Rationale for dual syntaxes: BioPAX must be widely accepted to be useful, dual syntaxes will facilitate this </li></ul>
  9. 9. Data stream organization <ul><li>Simple data packets for each object </li></ul><ul><ul><li>No nesting </li></ul></ul><ul><ul><li>Fully normalized (no repeat data) </li></ul></ul><ul><ul><li>Many internal pointers (i.e. “extra” data) needed </li></ul></ul><ul><ul><li>Objects (i.e. instances) are not self-contained </li></ul></ul><ul><li>Fully defined objects at every occurrence </li></ul><ul><ul><li>Highly nested </li></ul></ul><ul><ul><li>Not normalized (much repetition of data) </li></ul></ul><ul><ul><li>No internal pointers needed </li></ul></ul><ul><ul><li>Self-contained objects, even those of complex classes like “interaction” and “pathway” </li></ul></ul><ul><li>Ultimate structure of BioPAX record will likely lie between these two extremes </li></ul>
  10. 10. BioPAX Ontology : Root <ul><li>Root class: Entity </li></ul><ul><ul><li>Any concept that we will refer to as a discrete unit when describing the biology of pathways. </li></ul></ul><ul><ul><li>Does not include metadata </li></ul></ul><ul><ul><ul><li>E.g. “DB source”, “PubMed ID”, “Experimental technique”, etc. </li></ul></ul></ul>
  11. 11. BioPAX Ontology : Root <ul><li>Entity Subclass: Part </li></ul><ul><ul><li>A building block of simple interactions </li></ul></ul><ul><ul><li>E.g. Small molecules, Proteins, DNA, RNA </li></ul></ul><ul><li>Entity Subclass: Interaction </li></ul><ul><ul><li>A set of entities and some relationship between them </li></ul></ul><ul><ul><li>E.g. Reactions, Molecular Associations, Catalyses </li></ul></ul><ul><li>Entity Subclass: Pathway </li></ul><ul><ul><li>A set of interactions </li></ul></ul><ul><ul><li>E.g. Glycolysis, MAPK, Apoptosis </li></ul></ul>IS A HAS A
  12. 12. BioPAX Ontology: Parts <ul><li>Cell </li></ul><ul><ul><li>A specific type of cell (e.g. cardiac myocyte, B lymphocyte). </li></ul></ul><ul><li>Cell Component </li></ul><ul><ul><li>Part of a cell (e.g. nucleus, mitochondrion). The Gene Ontology contains a large list in the ‘cellular component’ ontology. </li></ul></ul><ul><li>DNA </li></ul><ul><ul><li>Deoxyribonucleic acid (e.g. the EGFR DNA sequence; see GenBank for more examples). </li></ul></ul><ul><li>Environment </li></ul><ul><ul><li>A physical or environmental effect (e.g. calcium wave, electric shock, heat, mechanical stress). </li></ul></ul><ul><li>Photon </li></ul><ul><ul><li>Light at some intensity and wavelength (e.g. UV light). </li></ul></ul><ul><li>Protein </li></ul><ul><ul><li>A protein (e.g. the EGFR protein sequence; see Swiss-Prot for more examples). </li></ul></ul><ul><li>RNA </li></ul><ul><ul><li>Ribonucleic acid (e.g. messengerRNA, microRNA, ribosomalRNA) </li></ul></ul><ul><li>Small Molecule </li></ul><ul><ul><li>A non-polymeric biomolecule. Generally, any bioactive molecule that is not a peptide, protein, DNA, RNA or possibly not a complex carbohydrate (e.g. glucose, penicillin) </li></ul></ul>
  13. 13. BioPAX Ontology: Interactions <ul><li>Control </li></ul><ul><ul><li>The control of a process (e.g. enzyme catalysis controls a biochemical reaction, gene regulation controls gene expression). </li></ul></ul><ul><li>Conversion </li></ul><ul><ul><li>A conversion process, which converts one set of entities to another set (e.g. a biochemical reaction converts substrates to products, the process of complex assembly converts single molecules to a complex, transport converts entities in one compartment to the same entities in another compartment). </li></ul></ul><ul><li>Molecular Association </li></ul><ul><ul><li>An association between a set of molecules (e.g. Arp2-Arp3 protein-protein interaction; protein complex e.g. the result of a co-immunoprecipitation experiment; hexokinase-glucose). </li></ul></ul><ul><li>Co-occurrence </li></ul><ul><ul><li>The co-occurrence of entities in some context. That context could be time, space, a sentence, sequence similarity space, etc. (e.g. Colocalization of a few receptors e.g. in a GPI anchored lipid raft; co-migration of cells; genes expressed at the same time). </li></ul></ul><ul><li>Equivalence Class </li></ul><ul><ul><li>A set of entities that can be considered equivalent in some context (e.g. a set of paralogs that can replace each other as enzymes in a biochemical reaction, a set of enzymes that may not be homologs, but are functionally identical e.g. glucose-6-phosphatase). </li></ul></ul><ul><li>Genetic </li></ul><ul><ul><li>A genetic interaction (e.g. a synthetic lethal interaction). An interaction between elements of a genotype that results in a change in phenotype. </li></ul></ul>
  14. 14. BioPAX Ontology <ul><li>Current structure of class hierarchy: </li></ul><ul><li>Will be implemented in: </li></ul><ul><ul><li>XML Schema </li></ul></ul><ul><ul><ul><li>Widely used </li></ul></ul></ul><ul><ul><li>OWL </li></ul></ul><ul><ul><ul><li>Powerful data representation </li></ul></ul></ul>
  15. 15. Use Cases <ul><li>A scientist studies particular Pathway </li></ul><ul><li>Toxicology study: given a pathway, are new compound/analogs connected? </li></ul><ul><ul><li>Requires: compounds/analogs, cross database search </li></ul></ul><ul><li>RNAi, KO: know genes, construct network, identify functional disruptor genes </li></ul>
  16. 16. Representing Metabolic Data in BioPAX EcoCyc: Reaction BioPAX Class: Reaction Glucose-6-p to fructose-6-p Name EC 0.4 kcal/mole Delta G <cml>fructose-6-phosphate</cml> Product <cml>glucose-6-phosphate</cml> Substrate 1 ID Reaction
  17. 17. Representing Metabolic Data in BioPAX (cont 1) EcoCyc: Enzyme Catalysis BioPAX Class: Catalysis 2 ID Low pH Inhibitors BioPAX ID=1 Reaction glucose-6-phosphate isomerase Enzyme Catalysis of glucose-6-p to fructose-6-p Name Catalysis
  18. 18. Representing Metabolic Data in BioPAX (cont 2) EcoCyc: Pathway BioPAX Class: Pathway 10 ID 1. BioPAX ID=2 2. BioPAX ID=4 3. BioPAX ID=6 etc. Interactions Glycolysis Name Pathway
  19. 19. Converting PSI Data into BioPAX PSI XML BioPAX Class: Molecular Association PDB:3HHR DB Source PMID = 1549776 Reference X-ray Crystallography Experiment Description hGHR binds to hGH Name hGRH; hGH Participants 1 ID Molecular Association
  20. 20. Signal Transduction DBs <ul><li>CSNDB </li></ul><ul><ul><li>Stores signal events as interactions between two proteins. </li></ul></ul><ul><ul><ul><li>E.g. “Grb2 -> Sos” </li></ul></ul></ul><ul><ul><li>Generates pathways automatically by: </li></ul></ul><ul><ul><ul><li>Displaying downstream interactions within a specific distance from a starting point </li></ul></ul></ul><ul><ul><ul><li>Or, finding the shortest path between two proteins </li></ul></ul></ul><ul><li>TRANSPATH – no longer publicly available; based on CSNDB </li></ul>CSNDB Pathway
  21. 21. BioPAX Subgroups <ul><li>Created for multiple purposes: </li></ul><ul><ul><li>Tackling specific conceptual problems </li></ul></ul><ul><ul><li>Developing spin-off projects </li></ul></ul><ul><ul><ul><li>Small Molecule Database </li></ul></ul></ul><ul><ul><ul><li>Database of Pathway Resources </li></ul></ul></ul><ul><ul><li>Gathering specific resources for core group </li></ul></ul><ul><li>Typically consist of: </li></ul><ul><ul><li>Core group members (1-3) </li></ul></ul><ul><ul><li>Experts from external community (1-2) </li></ul></ul>
  22. 22. BioPAX Subgroups: Small Molecule <ul><li>Evaluated CML 2.0 as means for exchanging small molecules </li></ul><ul><ul><li>No comprehensive small molecule DB exists </li></ul></ul><ul><ul><ul><li>Need to transfer entire small molecule structure, not just DB x-ref </li></ul></ul></ul><ul><ul><li>Proof of concept: </li></ul></ul><ul><ul><ul><li>EcoCyc small molecules CML 2.0 file </li></ul></ul></ul><ul><ul><ul><li>CML 2.0 file Shah lab visualization program </li></ul></ul></ul><ul><ul><ul><ul><li>No loss of information </li></ul></ul></ul></ul>
  23. 23. BioPAX Subgroups: States <ul><li>Determining best mechanism to represent biological states </li></ul><ul><ul><li>E.g. post-translational modification states of proteins, cell-cycle states </li></ul></ul>
  24. 24. BioPAX Subgroups: Examples <ul><li>Gathering sample data from various sources to illustrate use cases, promote practical development of BioPAX </li></ul>
  25. 25. Current Status <ul><li>Holding biweekly conference calls, bimonthly meetings </li></ul><ul><li>Finishing Level 1 Ontology </li></ul><ul><ul><li>Finishing slot definitions on Level 1 main-tree classes </li></ul></ul><ul><ul><li>Finishing class structure of side-trees </li></ul></ul><ul><ul><ul><li>States, provenance, evidence, timing </li></ul></ul></ul><ul><li>Working feverishly on presentation materials for ISMB 2003 </li></ul>
  26. 26. Next Steps <ul><li>Finish level 1 ontology in GKB </li></ul><ul><li>Implement ontology </li></ul><ul><ul><li>In OWL (easy) </li></ul></ul><ul><ul><li>In XML Schema (slightly less easy) </li></ul></ul><ul><li>Translate data from a few major DBs into BioPAX Level 1 </li></ul><ul><ul><li>Make revisions if necessary </li></ul></ul><ul><li>Release Level 1 </li></ul><ul><ul><li>By end of summer 2003 (hopefully) </li></ul></ul>
  27. 27. How to Contribute <ul><li>Participate in email list discussions to make your views heard </li></ul><ul><ul><li>sign up via web site: http://www. biopax .org </li></ul></ul><ul><li>Join a subgroup (if space) </li></ul><ul><li>Make your data available in BioPAX format, when complete </li></ul>
  28. 28. BioPAX Supporting Groups <ul><li>Groups </li></ul><ul><li>Memorial Sloan-Kettering Cancer Center: C. Sander, J. Luciano, M. Cary, G. Bader </li></ul><ul><li>University of Colorado Health Sciences Center: I. Shah </li></ul><ul><li>SRI Bioinformatics Research Group: P. Karp, S. Paley, J. Pick </li></ul><ul><li>BioPathways Consortium: J. Luciano ( ) </li></ul><ul><li>Argonne National Laboratory: N. Maltsev </li></ul><ul><li>Samuel Lunenfeld Research Insitute: C. Hogue </li></ul><ul><li>Harvard Medical School: Aviv Regev </li></ul><ul><li>Biopathways Consortium: Eric Neumann, Vincent Schachter </li></ul><ul><li>Collaborating Organizations: </li></ul><ul><li>Proteomics Standards Initiative ( </li></ul><ul><li>Chemical Markup Language ( ) </li></ul><ul><li>SBML ( </li></ul><ul><li>CellML ( </li></ul><ul><li>Databases </li></ul><ul><li>BioCyc ( </li></ul><ul><li>BIND ( </li></ul><ul><li>WIT ( </li></ul><ul><li>Grants </li></ul><ul><li>Department of Energy </li></ul>