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Protein Ontology: Addressing the need for precision in representing protein networks

Protein Ontology: Addressing the need for precision in representing protein networks. Workshop on Ontologies of Cellular Networks March 2008. Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant Professor, GUMC. TGF- b signaling pathway.

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Protein Ontology: Addressing the need for precision in representing protein networks

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  1. Protein Ontology: Addressing the need for precision in representing protein networks Workshop on Ontologies of Cellular Networks March 2008 Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant Professor, GUMC

  2. TGF-b signaling pathway Example from: INOH Event Ontology IEV_0000090 IEV_0000157 1 Phosphorylation of R-smad by TGF beta receptor I TGF beta receptor I R-smad IEV_0000159 2 Complex formation of R-smad and Smad4 Cytoplasm R-smad Smad4 IEV_0000158 m b me rane 3 Nuclear import of R-smad:smad4 lear R-smad: nuc smad4 Nucleus IEV_0000156 4 Binding of R-smad:smad4 complex and responsive element R-smad: smad4 responsive element IEV_0000155 5Transcription by R-smad:smad4 smad4 R-smad: part_of Actions Roles Locations

  3. The Roles Played Example from: INOH Molecule Role Ontology IMR_0100315 Smad4 IMR_0100310 Smad1 IMR_0100312 Smad3 IMR_0000372 Co-Smad IMR_0000369 Txn regulator IMR_0000370 SMAD IMR_0000371 R-Smad IMR_0100311 Smad2 IMR_0704004 SMAD2_HUMAN IMR_0000373 I-Smad IMR_0100313 Smad5 IMR_0100314 Smad8 is_a sequence_of

  4. Mothers against decapentaplegic homolog 2 Smad 2 GO annotation of SMAD2_HUMAN: Cellular Component: - nucleus Molecular Function: - protein bindingBiological Process: - signal transduction - regulation of transcription, DNA-dependent

  5. TGF-b TGF-beta receptor II I Smad 2 1 phosphorylation Smad 4 Smad 2 P P ERK1 CAMK2 2 complex formation Smad 2 P P P P Smad 2 P P P P Smad 4 Cytoplasm 3 nuclear translocation Smad 2 P P P Smad 4 Nucleus 4 DNA binding 5 Transcription Regulation ++

  6. Smad 2 P P Smad 2 P P P Smad 2 P P P Smad 2 P P x Smad 2 SMAD2_HUMAN Smad 2 SMAD2_HUMAN SMAD2_HUMAN SMAD2_HUMAN SMAD2_HUMAN Smad 2 SMAD2_HUMAN SMAD2_HUMAN

  7. %PRO:00000010 Smad2 %PRO:00000011 Smad2 isoform 1 (long form) %PRO:00000012 Smad2 isoform 1 phosphorylated form %PRO:00000013 Smad2 isoform 1, TGF-b receptor I-phosphorylated %PRO:00000014 Smad2 isoform 1, TGF-b receptor I and ERK1-phosphorylated has_modificationMOD:O-phosphorylated L-serine has_modificationMOD:O-phosphorylated L-threonine has_function GO: TGF-b receptor, pathway-specific cytoplasmic mediator activity has_function GO:SMAD binding has_function GO:transcription coactivator activity participates_in GO:signal transduction participates_in GO:SMAD protein heteromerization participates_in GO:regulation of transcription, DNA-dependent located_in GO:nucleus part_of GO:transcription factor complex %PRO:00000015 Smad2 sequence 1, TGF-b receptor I and CAMK2-phosphorylated %PRO:00000016 Smad2 sequence 2 (short form) - splice variant %PRO:00000017 Smad2 sequence 2 phosphorylated form %PRO:00000018 Smad2 sequence 2, TGF-b receptor I-phosphorylated %PRO:00000019 Smad2 sequence 3 - genetic variant related to colorectal carcinoma %PRO:00000015 Smad2 isoform 1, TGF-b receptor I and CAMK2-phosphorylated %PRO:00000016 Smad2 isoform 2 (short form) - splice variant %PRO:00000017 Smad2 isoform 2 phosphorylated form %PRO:00000018 Smad2 isoform 2, TGF-b receptor I-phosphorylated %PRO:00000019 Smad2 isoform 3 - genetic variant related to colorectal carcinoma arises_fromSO: amino_acid_substitution NOT has_modificationMOD: phosphorylated residue NOT has_function GO: transcription coactivator activity gives_rise_toDO: carcinoma of the large intestine

  8. Pfam Domain PRO http://pir.georgetown.edu/pro protein domain protein Root Level is_a has_part GOGene Ontology • Family-Level Distinction • In common: specific ancestor • Source: PIRSF family translation product of an evolutionarily-related gene molecular function is_a has_function • Gene-Level Distinction • In common: specific gene • Sources: PIRSF subfamily, Panther subfamily biological process translation product of a specific gene participates_in is_a cellular component • Sequence-Level Distinction • In common: specific allele or splice variant • Source: UniProtKB part_of (for complexes) located_in(for compartments) translation product of a specific mRNA is_a DO/UMLS Disease • Modification-Level Distinction • In common: specific translation product • Source: UniProtKB disease cleaved/modified translation product agent_of SOSequence Ontology Example: TGF-b receptor phosphorylated smad2 isoform1 is a phosphorylated smad2 isoform1 is a smad2 isoform 1 is a smad2 is a TGF-b receptor-regulated smad is a smad is aprotein ProForm sequence change Modification Level Sequence Level arises_from(sequence change) gives_rise_to (effect on function) Gene Level ProEvo PSI-MODModification Family Level Root Level protein modification has_modification

  9. TGF-b signaling pathway Example from: INOH Event Ontology IEV_0000090 IEV_0000157 P P 1 Phosphorylation of R-smad by TGF beta receptor I TGF beta receptor I smad2 R-smad P IEV_0000159 P P 2 Complex formation of R-smad and Smad4 Cytoplasm R-smad Smad4 smad2 P has_participantPRO:smad4 has_participantPRO:TGF-b receptor-phosphorylated smad2 has_participantPRO:smad4 has_participantPRO:TGF-b receptor & ERK1-phosphorylated smad2 IEV_0000158 m b me rane P P 3 Nuclear import of R-smad:smad4 lear R-smad: nuc smad2: smad4 P Nucleus IEV_0000156 P P 4 Binding of R-smad:smad4 complex and responsive element R-smad: smad2: smad4 responsive element P IEV_0000155 P P 5Transcription by R-smad:smad4 Transcription smad4 smad2: R-smad: Actors part_of P Actions Roles Locations

  10. http://pir.georgetown.edu/pro PRO Team (so far…) • Principle Investigators • Cathy Wu (PIR at GUMC) • Judith Blake (The Jackson Laboratory) • Barry Smith (SUNY Buffalo) • Curators & Developers • Cecilia Arighi (PIR at GUMC) • Winona Barker (PIR at GUMC) • Harold Drabkin (The Jackson Laboratory) • Zhang-zhi Hu (PIR at GUMC) • Hongfang Liu (GUMC) • Darren Natale (PIR at GUMC) Official Launch: March 31, 2008

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