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Regulating the Gene Ontology

This article discusses the regulation of gene ontology and the issues with current implementation, as well as proposed solutions and future directions. It presents the use of logical definitions and new relationships to accurately portray biological processes.

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Regulating the Gene Ontology

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  1. Regulating the Gene Ontology Where we’ve been and where we’re going

  2. Chris Mungall Berkeley Jane Lomax Cambridge David Hill Bar Harbor Tanya Berardini Palo Alto The Culprits

  3. In the Beginning, There Were Two Relationships • is_a: denotes a subtype of its parent. • chloroplast is_a organelle • part_of: denotes a portion of a parent • chloroplast stroma part_of chloroplast

  4. Regulatory functions made our lives difficult Protein kinase activity can be broken down into a catalytic function and a regulatory function Used part-of relationship to solve the 'protein kinase' (multipart protein function) problem. E.g. protein kinase activity part_of: protein kinase catalyst activity part_of: protein kinase regulator activity Gene Ontology Meeting February 25-26, 2000 We discussed how to handle regulatory activities in enzymes. Although the implementation is no longer valid for molecular function, the idea of using part_of to describe ‘regulators’ stuck.

  5. So, what’s the issue with regulates? • Regulation is not always an inherent part of the process that it regulates A speed-bump regulates the velocity of my car 50 mph 5 mph

  6. All along we’ve been making ‘regulation’ Terms

  7. We made the ‘regulation of X’ a part_of ‘X’ But it’s not really part_of

  8. We needed a better way to express ‘regulates’ • Regulation of X = “Any process that modulates the frequency, rate or extent of X.” • Where X can be: • a Biological Process • a Molecular Function • a Biological Quality

  9. Step 1: The is_a complete project All process in the Biological Process Ontology are subtypes of other biological processes. What types of regulatory processes are in the ontology?

  10. Chris ran an analysis on the live ontology to see if whenever we had a regulation of a biological process, it was a valid biological process. Step 2: Reality Check

  11. Step 3: Lots of Skype and WebEx between Maine and California

  12. Step 4: Using the Reasoner • Decomposed all the regulates terms into regulates and the process they are regulating (created logical definitions)

  13. A ‘Decomposed’ Term [Term] id: GO:0000019 name: regulation of mitotic recombination namespace: biological_process def: "Any process that modulates the frequency, rate or extent of DNA recombination during mitosis." [GOC:go_curators] synonym: "regulation of recombination within rDNA repeats" NARROW [] is_a: GO:0000018 ! regulation of DNA recombination intersection_of: GO:0065007 ! biological regulation intersection_of: regulates GO:0006312 ! mitotic recombination relationship: regulates GO:0006312 ! mitotic recombination The intersection tags make up the logical definition. This places the ‘regulation’ term in the context of mitotic recombination.

  14. Decomposition is good! DNA metabolic process --[i] DNA recombination ----[i] meiotic recombination regulation of DNA metabolic process --[i] regulation of DNA recombination ----[i] regulation of meiotic recombination

  15. Step 4: Using the Reasoner • Identified inconsistencies between the ‘regulates’ hierarchy and the rest of biological process • Identified missing links • Identified more specific and complete is_a parentage for ‘regulation’ terms.

  16. Now the ‘regulates of mitotic recombination’ part of the graph is consistent with ‘mitotic recombination’ This is the way the biological process ontology looks today!

  17. Step 5: In person meeting, 3 brains in one room are better than one • We used the reasoner to ‘check’ all of the is_a links in ‘regulation’ vs the target processes • Stats: • 969 new links • 302 deleted links

  18. regulates regulates regulates The Future!

  19. On March 25th [Term] id: GO:0000019 name: regulation of mitotic recombination namespace: biological_process def: "Any process that modulates the frequency, rate or extent of DNA recombination during mitosis." [GOC:go_curators] narrow_synonym: "regulation of recombination within rDNA repeats" [] is_a: GO:0000018 ! regulation of DNA recombination relationship: part_of GO:0006312 ! mitotic recombination [Term] id: GO:0000019 name: regulation of mitotic recombination namespace: biological_process def: "Any process that modulates the frequency, rate or extent of DNA recombination during mitosis." [GOC:go_curators] synonym: "regulation of recombination within rDNA repeats" NARROW [] is_a: GO:0000018 ! regulation of DNA recombination intersection_of: GO:0065007 ! biological regulation intersection_of: regulates GO:0006312 ! mitotic recombination relationship: regulates GO:0006312 ! mitotic recombination

  20. What does this buy us? • The new relationships portray the biology more accurately than part_of currently does • Regulates • Positively regulates • Negatively regulates • The new logical definitions allow automated consistency checks as the ontology is developed. • The first implementation of cross-products in GO • Sets the stage for: • Molecular function -> biological process • Cell type -> biological process • CheBI -> biological process

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