Protein Ontology (PRO)

Amherst, NYMay 15, 2013

Cathy H. Wu, Ph.D.Director, Protein Information Resource (PIR)

Edward G. Jefferson Chair and DirectorCenter for Bioinformatics & Computational Biology, University of Delaware

Professor of Biochemistry & Molecular Biology, Georgetown University

PRO-PO-GO Meeting

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 complexesNatale 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]

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)

3

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

PRO in Biological Context

Representation of protein forms & complexes in pathways/networks

9

TGF-b Signaling Pathway

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

Plant PRO Terms

10

Plant PRO Terms

Arabidopsis thaliana: Protein classes, forms and complexes related to cullin-containing complexes and brassinosteroid (BR) signaling

Cullin-Related PRO Terms

11

Hierarchical View: Cullin-Related Terms

12

13

Cytoscape View: Cullin-Related Terms

13

Cytoscape & Entry Views: Cullin-Related Terms

14

Cullin-1 in SCF complexes

• SCF Complexes formed in response to auxin and jasmonate signaling

• Link to ChEBI for small molecule-containing complexes

Cullin-1 Rubylated

15

Core proteins and other associated proteins annotated with GO related to BR signaling pathway (blue)

BR Signaling Pathway

16

Connecting protein forms and complexes with annotation => Modeling biology

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?

iPTM Network

Coupled with functional annotation and biological context (homology, disease, tissue/cell..)=> Hypothesis generation and discovery

17

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