1 / 16

Gene3D, Orthology and Homology-Based Inheritance of Protein-Protein Interactions

Gene3D, Orthology and Homology-Based Inheritance of Protein-Protein Interactions. Corin Yeats yeats@biochem.ucl.ac.uk http://gene3d.biochem.ucl.ac.uk/. The Gene3D Protein Family and Annotation Resource:. Identify sequence homologues of CATH domains

sho
Download Presentation

Gene3D, Orthology and Homology-Based Inheritance of Protein-Protein Interactions

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Gene3D, Orthology and Homology-Based Inheritance of Protein-Protein Interactions Corin Yeats yeats@biochem.ucl.ac.uk http://gene3d.biochem.ucl.ac.uk/

  2. The Gene3D Protein Family and Annotation Resource: • Identify sequence homologues of CATH domains • HMMs & hit resolution protocol DomainFinder. • UniProt, RefSeq, Ensembl (with generous help of SIMAP at MIPS). • Integrate with sequence annotation resources. • Pfam, GO, KEGG, UniProt annotation, IntAct, String • Flexible cross-resource comparisons, including CATH PDB domains. • Import sequence families - In-house OrthoFams, HAMAP, SIMAP clusters.

  3. {A} Last Common Ancestor A’ A Species 1 Species 2 Defining Orthology W.M. Fitch (1970) Distinguishing homologous from analogous proteins. Syst. Zool.19:99–113.

  4. {A} Last Common Ancestor {a} A’ A a’ Species 1 Species 2 Defining Paralogy W.M. Fitch (1970) Distinguishing homologous from analogous proteins. Syst. Zool.19:99–113. a

  5. {A} Last Common Ancestor A’’ A A’’’ A’ Co-orthologues Species 1 Species 2 Co-orthology

  6. Updating The Terminology: * E.L.L. Sonnhammer & E.V. Koonin (2002) Orthology, paralogy and proposed classification for paralog subtypes. TiG18:619-620. • InParalogues: • “paralogs in a given lineage that all evolved by gene duplications that happened after the radiation (speciation) event that separated the given lineage from the other lineage under consideration” • OutParalogues: • “paralogs in the given lineage that evolved by gene duplications that happened before the radiation (speciation) event”

  7. Defining “Ortholog Families”: • Strict Definition: • Families split at every duplication event. • Many small families. • Normal Definition: • Set root at appropriate level of interest. • Accept inparalogues. • More useful for function prediction.

  8. Some Example Resources:

  9. APC Prot A CD-HIT Prot C …. Near Identical Creating the OrthoFams: SIMAP protein similarity matrix UniProt & RefSeq Prot A Prot B Prot C Prot D ….

  10. A Simple Test of the OrthoFams: • 99.9% OrthoFams map to one HAMAP family in bacteria. • Each HAMAP family tends to map to several OrthoFams => Too conservative? • >80% map to a single KEGG Orthologue term.

  11. Inheriting Protein-Protein Interactions: • Protein-protein interactions (including mechanism) can be conserved after gene duplication and speciation events. • Some interactions are ancient and well conserved, many are not. • Interactions within species are better conserved between homologues than between species. • Interactions are not binary, but are based on affinity • Not all detectable interactions are biologically relevant. Refs: Mika & Rost 2006, Shoemaker & Panchenko 2007

  12. Interaction Inheritance Approaches: • Homology-based approaches have struggled… • Mika & Rost, 2007 • Problems: • High coverage or high quality input, not both. • Interaction networks re-arrange rapidly • No simple universal accurate sequence identity threshold can be found. • Need to separate those that can be inherited reliably, and those that can’t.

  13. The hiPPI Idea:homology inferred Protein-Protein Interactions • Assume OrthoFams provide more reliable functional groupings than simple similarity measures. • Assume high affinity ~= high conservation ~= low experimental false positive rate. • Require more than one piece of supporting evidence.

  14. iLevel cLevel S30 …. S100 Hs Mm Ce ? Hs ? Mm Mm S30 …. S100 Hs Mm Ce Hs ? Mm Ofam A Ofam B

  15. Interactions derived from MIPS, IntAct and MINT. • GO Term semantic similarity calculated with the Lord method (Lord et al, 2003).

  16. Links and References http://gene3d.biochem.ucl.ac.uk/ “Gene3D: comprehensive structural and functional annotation of genomes” Corin Yeats, Jonathan Lees, Adam Reid, Paul Kellam, Nigel Martin, Xinhui Liu, and Christine Orengo NAR (2008) 36:D414–D418.

More Related