Annotating from phenotypes: Difference between revisions

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=Introduction=
=Introduction=
Mutants can provide useful insights into a protein's function. GO annotations based on a phenotype should represent the normal function that can be inferred from the mutant. GO does not aim to capture individual phenotypes; use phenotype annotation resources for this purpose. The following guidelines should help determine how to annotate the function of a protein that can be inferred from its observed phenotypes.  
Mutants can provide useful insights into a protein's function. GO annotations based on a phenotype should represent the normal function that can be inferred from the mutant. GO does not aim to capture individual phenotypes; use phenotype annotation resources for this purpose. The following guidelines should help determine how to annotate the function of a protein that can be inferred from its observed phenotypes.  


===What is the normal molecular function ?===
===What is the normal molecular function ?===
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===Being ‘required for’ a process does not mean a protein is ‘part of’ a process===
===Being ‘required for’ a process does not mean a protein is ‘part of’ a process===
apoE example? https://www.uniprot.org/uniprot/P02649
apoE example? https://www.uniprot.org/uniprot/P02649


===Pleiotropic effects should not usually be captured===
===Pleiotropic effects should not usually be captured===

Revision as of 09:52, 6 November 2018

Introduction

Mutants can provide useful insights into a protein's function. GO annotations based on a phenotype should represent the normal function that can be inferred from the mutant. GO does not aim to capture individual phenotypes; use phenotype annotation resources for this purpose. The following guidelines should help determine how to annotate the function of a protein that can be inferred from its observed phenotypes.

What is the normal molecular function ?

  • Remember that annotations are inferences from the evidence to a normal function/process.
  • If there is no MF known, any phenotype can only be annotated to ‘acts upstream of or within’ OR consider not making a GO annotation - it’s OK!
    • Q: Is it possible to have a gene product with a novel or unknown MF that is otherwise well characterized genetically such that it could be placed within a given pathway or process?

You can only annotate to a process if the MF can be placed in the process, for example in a GO-CAM model (or in a pathway model from a paper) Example: nuclear pore: BRR6 is involved in nuclear envelope organization, when mutated, causes nucleocytoplasmic transport defects, but is NOT involved in nuclear transport

Being ‘required for’ a process does not mean a protein is ‘part of’ a process

apoE example? https://www.uniprot.org/uniprot/P02649

Pleiotropic effects should not usually be captured

Pleiotropy and ‘required for’ a process does not mean a protein is ‘part of’ a process

For example: splicing factors are often required for cell cycle transition, but they are not part of the cell cycle transition A good clue is viability of mutants: inviable mutants often have pleiotropic phenotypes or they have a strong terminal phenotype that can easily be misinterpreted (cell cycle transition blocks/checkpoints, chromosome mis-segregation, etc) Beware of read-outs: DNA replication, apoptotic DNA fragmentation, etc)

Cell proliferation, cell migration and apoptosis

Mutants showing increased/decreased cell proliferation, cell migration and apoptosis need to be analyzed carefully. If we don’t know the underlying molecular/cellular mechanism, these annotations should not be made Mutually exclusive terms: cell proliferation should not be used for proteins involved generally in growth or division

Mutants and regulation

Mutants annotated to ‘regulation’ with no molecular function annotation (sometimes an annotation to a protein complex of with a known function) should be examined closely) should be reviewed When there is new knowledge, older IMP annotation should be reviewed and removed as required