Annotating from phenotypes: Difference between revisions
(Created page with "Complete from https://docs.google.com/presentation/d/1Akm-zNZWNXgyNOYZpgmzpzbkr8r9fNUJX8U2Yx5Guo4/edit#slide=id.g44f4f58dad_0_96 What is the normal molecular function ? Being...") |
mNo edit summary |
||
| Line 1: | Line 1: | ||
=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 ! | |||
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 | |||
[[Category: Annotation]] [[Category:Working Groups]] | [[Category: Annotation]] [[Category:Working Groups]] | ||
Revision as of 11:23, 5 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 ! 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