Yesterday, Andrew Su and I were wondering about disjointness in the Gene Ontology. We mused, "are there concepts in the GO that are mutually exclusive from the perspective of the gene products that they are associated with?" In other words, if a gene is anointed with a particular annotation, are there any other annotations that are thus rendered impossible for that gene?
With a small amount of searching, I found that the GO consortium is researching the addition of declarations of disjointness such as "intracellular is disjoint from extracellular". However, such statements about cellular space don't necessarily transfer to statements about the genes that occupy those spaces. This is clearly illustrated by 390 human proteins that are annotated as both 'intracellular' and 'extracellular' (and is stated explicitly in the GOC definition of 'Disjoint from'). So, even when/if that gets finished, its not going to help with our question. Furthermore, it seems that searching for the strict, perfect boundaries of formal logic might not be the right approach to this anyway.
What we would really like to see is a probability. Given that a gene is annotated with a particular concept from the GO, what is the probability that it could also be annotated with another GO concept? Concept pairs where the probability of co-annotation approaches zero would represent the (probably) disjoint biological classes that we were originally thinking about.
Naively, it seems this would be fairly easy to generate using the GO annotation database. Just build a contingency table for each pair of GO concepts (avoiding sub/superclasses) with counts for numbers of genes annotated with each concept and compute the statistics. If anyone would like to implement this (even better implement it in a non-naive way that accounted correctly for priors and chose the best test statistic) we would:
- be very happy to use the results in the context of another investigation that is already in progress and that motivated the question...
- be very happy to share authorship on any papers that might come out of the probabilistic partitioning service or the mysterious study already in progress...
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Partially related efforts but not quite what we are after...
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