Download `response to x` terms?

Response to Stimulus
Ruth Lovering
Thanks to Doug for agreeing to be slide monitor!
2. Why do we need ‘response to x’ terms?
Currently, these terms enable
curators to link a change in
morphology/phenotype following
stimulation of a cell with the stimulus
Example: Response to insulin
– Stimulation
of a cell with insulin leads to:
• uptake of glucose (GO:0046323 glucose import)
– Need distinguish set of genes:
• Involved in glucose import following insulin stimulation
• Involved in glucose import due to blood glucose levels per se
• Responsible for maintaining a basal rate of glucose uptake
– Use ‘cellular response to insulin stimulus’ and ‘glucose
import’ (column 16)
3. SourceForge Request Jesintha Maniraja
• The GO definition for ‘response to stimulus’ 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 may all be
considered as part of this process, including:
– Receptors
– Intracellular proteins directly bound to the receptor
– Subsequent downstream signaling molecules, caspase or kinase cascades
– Transcription factors
– Genes and proteins regulated by stimulus
• Genes and proteins regulated because their products are directly involved in
the morphological/phenotypical changes associated with the stimulated cell
• Gene and proteins required in the non-stimulated cell but no longer required in
the stimulated cell
– Proteins whose expression is NOT differentially regulated by stimulus, but
are necessary for response, eg proteins involved in secretion.
4. Current curation
• Need clarification of current curation practice
– Are the ‘response to x’ terms being used by curators for the
annotation of high-thoughput data following a stimulation
experiment?
– Are the ‘response to x’ terms being used by curators for the
annotation of only a limited number of specific processes?
– If both of these approaches are being taken we need to find a
solution which enables both approaches to continue but which
does not lead to a loss of information.
5. Possible approaches to resolving SF item
• If all groups are using ‘response to x’ terms for the annotation of
high-thoughput data following a stimulation experiment
– Refine GO term definition and include note to confirm this breadth
• If all groups are using ‘response to x’ terms for just a limited number
of the following proteins
– Agree on proteins to be covered, refine GO term definition and include
note to confirm the limitations (what is not to be included)
• If there is inconsistent use of ‘response to x’ across groups
– Define new child terms which can be used for specific subsets of
proteins, this would enable the broad parent terms to be used for highthroughput data, so no data would be lost.
– Agree on one or other approach and correct MOD data if required
– Refine GO term definition
6. Refine ‘response to x’ definition
• The current GO definition 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.”
• Need to clarify start and finish of process and possibly add or
remove processes/functional protein classes listed in brackets
• Which of the following to be covered by the GO term?
1. Receptors
2. Intracellular proteins directly bound to the receptor
3. Proteins involved in receptor internalisation
3. Subsequent downstream signaling molecules, caspase or kinase cascades
4. Transcription factors
5. Genes and proteins directly involved in the morphological/phenotypical changes
associated with the stimulated cell eg proteins involved in secretion, apoptosis, cell
cycle, biosynthetic processes
7. Are child terms to ‘response to x’ needed?
Based on curation practice decision is it appropriate to
consider the need for ‘response to x’ child terms? Such as:
Response to x
> x-mediated signal transduction
>> x-mediated signaling pathway
>> x-mediated intracellular signaling cascade
> Detection of x
> Regulated gene transcription in response to x
> Change in cell state in response to x
>> Production of y in response to x
>> Apoptosis in response to x
>> Cell growth in response to x
8. Summary
• Consistent curator approach to use of ‘response to x’
– High-throughput data
– limited set of proteins
• Refine definition of GO term
• Need for child terms of ‘response to x’?