Annotation 29Apr10

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IMP evidence code needs clarfication.

The issue is whether IMP GO annotations should be made from chemical inhibition studies in which a drug is used on whole cells to inhibit a specific protein. (Note, this is distinct from chemical genomics studies where a chemical is used in combination with a mutant collection; we do already curate these as mutant phenotypes.) An example is in this paper

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000294

C. albicans Tor1p is essential and there are no available reduction-of-function alleles, so they use the inhibitor rapamycin to reduce Tor1p function. Rapamycin-treated cells have increased expression of adhesin genes, so the authors conclude that Tor1p negatively regulates adhesion. Is an annotation to "negative regulation of adhesion" with IMP evidence justified? GOC documentation says that IMP can be used based on

"any procedure that disturbs the expression or function of the gene, including RNAi, anti-sense RNAs,
 antibody depletion, or the use of any molecule or experimental condition that may disturb or affect 
the normal functioning of the gene, including: inhibitors, blockers, modifiers, any type of antagonists,
temperature jumps, changes in pH or ionic strength." 

Rapamycin has a lot of effects, such as inhibiting expression of genes involved in ribosome biogenesis and other processes, which may or may not be due to its inhibition of Tor1p.

So, annotating based on chemical inhibition is not a good idea unless you know the chemical is very specific. This bit should be highlighted in the evidence code documentation.


Pascale: tor is widely accepted as the Target of Rapamycin. tor has a very central role in regulation of protein synthesis, so one would expect pleiotropic effects from its inactivation. In other words, I can see how this is very downstream, but it's not inconsistent with annotating RNA polymerase to embryonic development. I'll add this in the 'downstream effect discussion.


Management of WG email lists

  • Could the WG email lists be administered by a person in addition to Mike? As it would be handy to keep an eye on who has signed up/ who has not when sending emails round (Emily)

ATP catabolism for Kinase activity

If a geneproduct has kinase activity, would you make ATP binding and ATP catabolic process annotations? Pascale will email David, Tanya, Chris.