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Protein Ontology (PRO)

Protein Ontology (PRO). PRO-PO-GO Meeting. Amherst, NY May 15, 2013 Cathy H. Wu, Ph.D. Director, Protein Information Resource (PIR) Edward G. Jefferson Chair and Director Center for Bioinformatics & Computational Biology, University of Delaware

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Protein Ontology (PRO)

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  1. Protein Ontology (PRO) PRO-PO-GO Meeting Amherst, NY May 15, 2013 Cathy H. Wu, Ph.D. Director, Protein Information Resource (PIR) Edward G. Jefferson Chair and Director Center for Bioinformatics & Computational Biology, University of Delaware Professor of Biochemistry & Molecular Biology, Georgetown University

  2. Protein Ontology (PRO) Reference Ontology for Proteins One of the first set of six OBO Foundry ontologies PRO in OBO Foundry The Protein Ontology: a structured representation of protein forms and complexes Natale DA, Arighi CN, Barker WC, Blake JA, Bult CJ, Caudy M, Drabkin HJ, D'Eustachio P, Evsikov AV, Huang H, Nchoutmboube J, Roberts NV, Smith B, Zhang J, Wu CH. (2011) Nucleic Acids Res. 39, D539-545 [PMID:20935045]

  3. PRO in OBO Foundry Reference Ontology for Proteins Capture knowledge about proteins to model biology Three sub-ontologies: connect protein types necessary to model biology Ontology for Protein Evolution (ProEvo): Captures protein classes reflecting evolutionary relatedness of whole proteins Ontology for Protein Forms (ProForm): Captures different protein forms of a given gene locus from genetic variations, alternative splicing, proteolytic cleavage, post-translational modifications (PTMs) Ontology for Protein Complexes (ProComp): Captures distinct complexes as they exist in different species ; defines complexes through component proteins Protein Ontology (PRO)

  4. PRO Overview: ProEvo • Ontology for Protein Evolution (ProEvo): Captures protein classes reflecting evolutionary relatedness of whole proteins

  5. PRO Overview: ProForm • Ontology for Protein Forms (ProForm): Captures different protein forms of a given gene locus from genetic variations, alternative splicing, proteolytic cleavage, post-translational modifications (PTMs) => “proteoforms”

  6. PRO Overview: ProComp • Ontology for Protein Complexes (ProComp): Captures distinct complexes as they exist in different species; defines complexes through component proteins Serine Palmitoyltransferase (SPT) Complex

  7. Why PRO • Provides formalization to support precise annotation of specific protein classes/forms/complexes, allowing accurate and consistent data mapping, integration and analysis • Allows specification of relationships between PRO and other ontologies, such as GO, SO (Sequence Ontology), PSI-MOD, ChEBI, MIM/Disease Ontology, CL (Cell Ontology), PO (Plant Ontology)/cROP • Provides stable unique identifiers to distinct protein types • Provides a formal structure to support computer-based reasoning based on homology and shared protein attributes, including “ortho-isoform,” “ortho-modified form”

  8. PRO Framework • PRO (ProForm, ProEvo, ProComp) is aligned with other OBO Foundry ontologies under the umbrella of the Basic Formal Ontology (BFO) • PRO terms are defined/annotated using other ontologies and resources via definition of relations or mappings when appropriate

  9. PRO in Biological Context • Representation of protein forms & complexes in pathways/networks TGF-b Signaling Pathway

  10. Plant PRO Terms Arabidopsis thaliana: Organism-Gene level terms (UniProtKB) mapped to Gene level terms (PRO) based on PANTHER mapping of 12 reference genomes

  11. Plant PRO Terms • Arabidopsis thaliana: Protein classes, forms and complexes related to cullin-containing complexes and brassinosteroid (BR) signaling Cullin-Related PRO Terms

  12. Hierarchical View: Cullin-Related Terms

  13. CytoscapeView: Cullin-Related Terms 13

  14. Cytoscape & Entry Views: Cullin-Related Terms

  15. Cullin-1 in SCF complexes Cullin-1 Rubylated • SCF Complexes formed in response to auxin and jasmonate signaling • Link to ChEBI for small molecule-containing complexes

  16. BR Signaling Pathway Connecting protein forms and complexes with annotation => Modeling biology Core proteins and other associated proteins annotated with GO related to BR signaling pathway (blue)

  17. iPTM Network • Exploring Relations • Substrate-centric: • What PTM forms of a protein and their modifying enzymes are known? • Enzyme-centric: • What substrates are known for a given PTM enzyme? • Interaction: • What interacting partners are known for each PTM form of a given protein? • Pathway: • What protein modifications and enzymes are known in a given signaling pathway? • Coupled with functional annotation and biological context (homology, disease, tissue/cell..) • => Hypothesis generation and discovery

  18. PRO Dissemination • PRO Website (http://www.proconsortium.org) • Searching, browsing, downloading • PRO Views • Entry view • Table summary • OBO stanza, OWL • Ontology hierarchy • Cytoscape network • PRO Link: Persistent URL: http://purl.obolibrary.org/obo/PR_xxxxxxxxx • OBO Foundry (http://www.obofoundry.org/) • NCBO Bioportal (http://bioportal.bioontology.org/) • Reciprocal links from/to collaborative resources

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