Annotation consistency: 'Response to' terms: Difference between revisions

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The advantage would be that it would encourage curators to consider what part of the response process their protein is involved in.
The advantage would be that it would encourage curators to consider what part of the response process their protein is involved in.
Emily: I agree that the standard definition of 'response to' terms is too broad, and enables a wide range of gene products to be annotated.
- producing annotations such as: IDA annotations where curators have read evidence of their protein seen to change subcellular location (movement) as a result of a specific stimulus, IDA annotations where investigators have measured the increase of a particular protein's catalytic activity in response to some stimulus.
- perhaps such annotations should only be created if there is additional information on the roles the proteins are involved in with regards to such a response, so in a similar vein with Ruth, I'd be tempted to encourage curators to annotate more often to more descriptive terms underneath a 'response to x' term, and for this term to only be used by external users for slimming purposes.
Requiring annotation to such granular terms would, I imagine, reduce the frequency with which IEP annotations could made to such terms en masse..?


==2. Proposed solution(s)==
==2. Proposed solution(s)==

Revision as of 09:47, 14 October 2008

Group Members

(anyone can add themselves)

  • Tanya Berardini, Emily Dimmer, Pascale Gaudet, Ruth Lovering, Alexander Diehl

1. Issue

The 'response' terms have been in GO since the very beginning. Examples:

   GO:0006950	OS	stress response
   GO:0006951	OS	heat shock response

The definitions of the 'response to x' terms are quite broad and have been this way since they were first introduced. (as far as I can tell from going back in time in the GO.defs files back to Sept. 2001)

"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 ..."

The broadness of the definition leads to questions like these:

  • When do we annotate to these terms?
    • When a gene product is up-regulated following a stimulation should it be annotated to 'response to this stimulus'?

For example, should cell cycle genes up-regulated by insulin be included in 'response to insulin stimulus'?

Possibly the definition is so broad that all up-regulated genes could be included. But is this the intention of GO?

    • How far down a series of events do we annotate a protein to the process?

For example GO:0032868 response to insulin stimulus Definition: 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 an insulin stimulus.

If we look at wikipedia's comments on the effects of insulin: http://en.wikipedia.org/wiki/Insulin then we would expect that insulin stimulation will cause changes to a wide variety of metabolic pathways and transport systems and increases in cell division associated pathways (replication, protein synthesis, cell cycle etc) etc.

I would have thought that the proteins associated with the 'response to insulin stimulus' would be: receptors detecting the stimulus, transducers ensuring that the response to insulin is initiated by the cell and that proteins involved in the change of the cell itself would not be included, ie not including proteins involved in the storage of glucose in liver (and muscle) cells in the form of glycogen.

Should insulin be associated with GO:0032868 response to insulin stimulus?

    • Is there inconsistency in the annotation of proteins to these terms? If there is, is this related to whether the annotation is to multicellular organism or singled cell organism?
  • Are there certain evidence codes that should/should not be used when annotating to these terms?
    • Review of existing evidence codes used


From GO database:

   +-----------------+
   | code | count(*) |
   +------+----------+
   | IEA  |    82721 |
   | IEP  |     2849 |
   | IMP  |     2246 |
   | ISS  |     2492 |
   | IDA  |     1233 |
   | NAS  |      207 |
   | RCA  |      443 |
   | TAS  |      469 |
   | IGI  |      394 |
   | IC   |      126 |
   | IPI  |       21 |
   | ISO  |       13 |
   | NR   |        8 |
   +------+----------+

TAIR case: mostly IEP (majority are from Northern or RT-PCR experiments, fewer microarray), then about equal amounts of IMP (treat the mutant with a substance, don't get a response where you get one in the wild type or the reverse), ISS (TIGR inherited), IEA (INTERPRO2GO), fewer annotations with IGI, TAS, IDA, NAS

Ruth: I am starting to change my mind a bit on this one. I wondered if perhaps what is needed is more child terms to the response_to terms so that it is clearer whether the gene is involved in the signal transduction from receptor to transcription or in the effector side, covering morphological changes, apoptosis, cytokine synthesis etc. With appropriate regulation terms included. At present the use of 'response_to' terms are being lost because such a large number of genes are being annotated to them. If we have slightly more specific terms (but still quite general otherwise we will just be duplicating all the signal transduction terms etc) then the association of (for example) a gene product involved in sensing a specific stress will not get lost amongst apoptotic genes.

I realise that GO terms often only get created when the term is needed, but I think it would be useful to try to standardise the available options for these terms. So how about all response to terms have the following set up where appropriate):

response to x > detection of x > cellular response to x >> x mediated signaling pathway >> regulation of transcription in response to (or by) x >> regulation of protein synthesis/post-transcriptional modifications in response to x >> change in cell state in response to x (eg morphology, apoptosis, activation, rigidity, motility, cell growth) > regulation of response to x > negative regulation of response to x > positive regulation of response to x

I guess the problem is that this would create a massive increase in terms if we took this to all possible regulation terms etc. Or even just adding these children to all the major response to terms (The majority of these terms already exist for at least one of the current response to terms and some are just listed under the response to extracellular stimulus term.)

The advantage would be that it would encourage curators to consider what part of the response process their protein is involved in.

Emily: I agree that the standard definition of 'response to' terms is too broad, and enables a wide range of gene products to be annotated.

- producing annotations such as: IDA annotations where curators have read evidence of their protein seen to change subcellular location (movement) as a result of a specific stimulus, IDA annotations where investigators have measured the increase of a particular protein's catalytic activity in response to some stimulus.

- perhaps such annotations should only be created if there is additional information on the roles the proteins are involved in with regards to such a response, so in a similar vein with Ruth, I'd be tempted to encourage curators to annotate more often to more descriptive terms underneath a 'response to x' term, and for this term to only be used by external users for slimming purposes. Requiring annotation to such granular terms would, I imagine, reduce the frequency with which IEP annotations could made to such terms en masse..?

2. Proposed solution(s)

Review the intention of the 'response to' GO terms. Consider identifying start and finish of the 'response to' process. More broadly, refine the scope of these terms to be more clear.

Come up with guidelines of what experimental assays would provide supporting evidence for annotations using these terms.

Should this go to the annotation group? Should this go on the Montreal agenda?

3. Comments/counter arguments

SourceForge issue opened: 'response to stimulus' http://sourceforge.net/tracker/index.php?func=detail&aid=2094943&group_id=36855&atid=440764 (Alex: I have now added comment to this entry.)

Other related SF items:

'response to stimulus' http://sourceforge.net/tracker/index.php?func=detail&aid=1601609&group_id=36855&atid=440764

'protein stimulus' http://sourceforge.net/tracker/index.php?func=detail&aid=1601557&group_id=36855&atid=440764

'regulation of response to tumor necrosis factor' http://sourceforge.net/tracker/index.php?func=detail&aid=2129906&group_id=36855&atid=440764

4. Proposed resolution

Back to Reference_Genome_Annotation_Project