2010 GO-camp Response to terms issues

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1. Background

(from old source forge item: [1])

The GO definition for response to stimulus (and similarly for many response to XXX terms) is, “ A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a specified stimulus.”

This definition seems to imply that a wide array of proteins, including receptors, intracellular proteins directly bound to the receptor, subsequent downstream signaling molecules, transcription factors and the genes that they regulate may all be considered as part of a response to a stimulus.

We desire clarification on this point, whether all these classes of proteins may be considered for curation of terms within the response to stimulus hierarchy, or should curation within this hierarchy be limited to only certain classes of proteins?


2. Review of current GO annotation practices

(Review of the annotation guidelines, questions/discussions)

Previous discussions:

  • Annotation_consistency:_'Response_to'_terms: In summary: how is 'response to' x different from 'x signaling pathway'?
  • Very good overview of the problem by Alex : Use_of_Response_To_Terms_in_Annotation
  • Evidence codes: Some people had annotated 'response to heat' by IDA for the heat shock protein; while what was measured was the level of transcript/protein. There are 38 genes annotated to 'response to heat shock' with IDA in the GO database. Those should be checked? (From July 18 Jamboree [2])
  • What experiment would provide valid IDA data for 'response to xx'? (From July 18 Jamboree [3])
  • Minutes from May 13th 2010 call

What's out there?

For June 2nd conference call

  • Annotations to response to stimulus and children:
    • total = 740 K annotations
    • IEP: 7663 annotations

Response to stimulus GO:0050896

    • IDA: 154 annotations by PseudoCAP
    • IC: 38 annotations by Gramene
    • IEP: 1 annotation by RGD
    • IMP: 2 annotations by MGI
    • There are also > 100 ISS/ISO, mostly by PseudoCAP
    • 25 pages (x how many per page? ) IEA
  1. Cellular response to stimulus GO:0051716
    • IDA: 5 annotations UniProt
    • ISS: 26 from UniProt
  2. response to external stimulus > 1,300 direct annotations
  3. response to extracellular stimulus: ~ 10 annotations, human, rat (including IEA)


Question 1: Are "cellular response and response to stimulus grouping terms? Is there any use to have annotations to that?

Children of cellular response to stimulus and related 'unqualified' responses

    • GO:0043482 : cellular pigment accumulation [view gene products] : no annotations to either GO:0043482 or its children
    • GO:0071214 : cellular response to abiotic stimulus [view gene products] no direct annotations
    • GO:0071216 : cellular response to biotic stimulus [view gene products] no direct annotations
    • GO:0070887 : cellular response to chemical stimulus [view gene products] 10 annotations
      • IEP: 5 annotations (4 RGD, 1 ASPGD)
      • IEA: 3 ensembl
      • IMP: 1 BHF-UCL
      • ISO: 1 RGD (based on human IMP)
    • GO:0031668 : cellular response to extracellular stimulus [view gene products] ~ 75 direct annotations
      • IDA: 32 MGI; 2 RGD
      • IEP: 5 RGD
      • IMP: 2 BHF-UCL; 3 MGI
      • IEA: 82 ensembl
      • ISS and related: 7 ISS, 18 ISO
    • GO:0033554 : cellular response to stress : 357 direct annotations
    • GO:0006950 response to stress ~ 300 direct annotations by EXP codes
      • IC: 3 annotations - pombe
        • IDA: 4 annotations by different groups
      • IEP: 260 annotations, >90% pombe
      • IGI: 8 annotations, pombe
      • IMP 40 annotations, mostly pombe, but also wormbase, EcoCyc, CGD
      • ISS, etc: 18: pombe, RGD, UniProt
      • RCA, TAS; 20, pombe
      • 3 IEA: hamap, CGD, ensembl

Question 2: should we make it a guideline that response to x annotations must be to more granular terms? ie, at lest response to UV, response to calcium, etc. We need to know what was tested.

    • GO:0034644 : cellular response to UV [view gene products]
    • GO:0007602 : phototransduction [view gene products]

3. Proposed annotation policy

  1. Avoid annotations to 'response to' terms by microarray experiments.
  2. High level 'Response to' terms *should not* be used *directly *for annotation. This includes the following terms:
    • GO:0050896 : response to stimulus
    • GO:0051716 : cellular response to stimulus
    • GO:0009628 : response to abiotic stimulus
    • GO:0009607 : response to biotic stimulus
    • GO:0042221 : response to chemical stimulus
    • GO:0009719 : response to endogenous stimulus
    • GO:0009605 : response to external stimulus
    • GO:0006950 : response to stress
    • GO:0048585 : negative regulation of response to stimulus
    • GO:0048584 : positive regulation of response to stimulus
    • GO:0048583 : regulation of response to stimulus

4. Examples (papers) and discussion of GO annotation issues

Transcription factors: O35780 (BHE40_RAT) is annotated to "entrainment of circadian clock" from PMID 12397359. The experiments show it is a transcription factor for genes involved in the circadian clock. Two questions: (i) is the term correct? or should it be annotated to the parent (regulation of circadian rhythm); or to both? (ii) is the IDA evidence code correct?

  • The F/P transcription regulator activity IDA annotations are missing. Is there any way we could have checks that would catch that?


  • PMID: 2071672 (proposed by Pascale)

What evidence code should be used to 'response to' annotations?

    • (A) For example in PMID: 2071672, the authors say "Exposure of the latter cells to 45 degrees C resulted in over 15-fold increase in the apparent level of the 25-kD IAP protein, confirming that its expression is regulated by heat shock". Should this protein (Q00649) be annotated to "response to heat" by IDA or IEP?
    • (B) Similar to (A) example: "Two highly divergent human MHC class I genes, MICA (Q29983) and MICB (Q29980), are regulated by promoter heat shock elements", protein: PMID: 8901601. Should this protein (Q00649) be annotated to "response to heat" by IDA or IEP?
    • (C) Q16576 Sc RBBP7 (aka RBAP46) is annotated to "cellular heat acclimation" by IDA from PMID:7503932. Is this annotation correct?

5. Suggestions for Quality Control procedures

  1. Check for all IDA annotations for the broad 'response to x terms'
  2. Check for cellular response vs response. Not sure of the best way to do this.
  3. High level 'Response to' terms *should not* be used *directly *for annotation. This includes the following terms:
    • GO:0050896 : response to stimulus
    • GO:0051716 : cellular response to stimulus
    • GO:0009628 : response to abiotic stimulus
    • GO:0009607 : response to biotic stimulus
    • GO:0042221 : response to chemical stimulus
    • GO:0009719 : response to endogenous stimulus
    • GO:0009605 : response to external stimulus
    • GO:0006950 : response to stress
    • GO:0048585 : negative regulation of response to stimulus
    • GO:0048584 : positive regulation of response to stimulus
    • GO:0048583 : regulation of response to stimulus



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