has_part in GO
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The document discusses the part-of relationship in ontologies and how it can be used incorrectly if additional context is not provided. While part-of indicates a location, it does not necessarily mean all instances of the parts are included. The document proposes adding a qualifier like "integral_to" to capture when a part is essential to a complex or process in a given species. This would allow reliable propagation of annotations while avoiding incorrect inferences from a simple part-of relationship alone.
has_part in GO
- 1. has_part : a new twist Original thinking gene products would not propagate over has_part has_part used as a navigational aid or in probabilistic inference has_part could be omitted from main ontology files with no loss of information In fact: There are situations where has_part can be used in annotation propagation
- 2. Motivation for has_part : An example of an incorrect use of part_of chromosome nucleus mitochondrion part_of part_of all chromosome part_of some nucleus all chromosome part_of some mitochondrion
- 3. Current GO: part-specific subtypes chromosome nucleus mitochondrion part_of nuclear chromosome miotchondrial chromosome part_of ABF1 MGM101 is_a is_a
- 4. propagation over part_of chromosome nucleus mitochondrion part_of nuclear chromosome miotchondrial chromosome part_of ABF1 MGM101 is_a is_a ABF1 MGM101
- 5. part-specific subtype pattern A common ‘design pattern’ in GO If p is located in w 1 or w 2 then create part-specific subtypes: p-in-w 1 is_a p and part_of w 2 p-in-w 2 is_a p and part_of w 2 Cons: ‘ clutters up’ ontology but terms can be managed automatically using reasoner Annotators may not see subtypes and annotate too generally Easy to fix with correct tooling? Pros: greater discriminative power, more specific annotations Logically coherent, easy to implement rules Then why not implement this universally?
- 6. Another example: erroneous use of part_of with complexes core TFIIH complex holo TFIIH complex NEF3 complex part_of TFB1 part_of we would not do this!!
- 7. core TFIIH complex (CURRENT GO) core TFIIH complex holo TFIIH complex NEF3 complex TFB1 part_of part_of core TFIIH portion of holo TFIIH complex core TFIIH portion of NEF3 complex is_a is_a
- 8. Problem: annotations to more generic term core TFIIH complex holo TFIIH complex NEF3 complex TFB1 part_of part_of core TFIIH portion of holo TFIIH complex core TFIIH portion of NEF3 complex is_a is_a
- 9. Problem: additional semi-redundant annotations required to capture necessary gene products core TFIIH complex holo TFIIH complex NEF3 complex TFB1 part_of part_of core TFIIH portion of holo TFIIH complex core TFIIH portion of NEF3 complex is_a is_a TFB1 TFB1 ABF1 MGM101
- 10. core TFIIH with has_part core TFIIH complex holo TFIIH complex NEF3 complex has_part has_part TFB1 Logically correct Can we propagate gene products?
- 11. We would like to propagate gene products in this case – but can we do this universally ? core TFIIH complex holo TFIIH complex NEF3 complex has_part has_part TFB1 TFB1 TFB1
- 12. thought experiment: use has_part for location-specific chromosomes chromosome nucleus mitochondrion has_part has_part ABF1 MGM101
- 13. no reliable propagation of gene products over has_part chromosome nucleus mitochondrion has_part has_part ABF1 MGM101 ABF1 MGM101 MGM101 ABF1
- 14. So what’s the difference in ontology structure? core TFIIH complex holo TFIIH complex NEF3 complex has_part has_part TFB1 chromosome nucleus mitochondrion has_part has_part ABF1 MGM101
- 15. So what’s the difference in ontology structure? there is no structural difference the computer needs some additional knowledge that is currently IMPLICIT core TFIIH complex holo TFIIH complex NEF3 complex has_part has_part TFB1 chromosome nucleus mitochondrion has_part has_part ABF1 MGM101
- 16. What’s the difference in annotations? core TFIIH complex TFB1 chromosome ABF1 MGM101 SOME instances of MGM10 proteins are part of SOME chromosomes SOME instances of TFB1 proteins are part of SOME core TFIIH complexes
- 17. What’s the difference in annotations? core TFIIH complex TFB1 chromosome ABF1 MGM101 SOME instances of MGM10 proteins are part of SOME chromosomes SOME instances of TFB1 proteins are part of SOME core TFIIH complexes ALL instances of core TFIIH complexes proteins has_part SOME TFB1 protein (in this species) TFB1 is integral to core TFIIH complex complex This crucial piece of knowledge is IMPLICIT NOT ALL instances of chromosome has_part SOME MGM10
- 18. Solution Add additional qualifier to GAF name TBD. integral_to? Semantics: ALL instances of this complex in this species have this gene product as part This is stronger than an existing annotation: some instance of this gene product in this species are found in this complex Also works for BP ALL instances of this process in this species require this gene product Example: spermatogenesis, meiosis, MSH standard annotation: some instance of this gene product actively participate in this process Works using standard DL reasoning technology Requires change in annotation practice