[Annotation] phenotype or GO-still struggling

Wed Jul 9 15:24:20 PDT 2008

I don't think the GOC has ever had a policy, or even a recommendation, 
that process annotations should be made from all mutant phenotypes, nor do 
I think that it should.

For example, SGD is currently working on annotating phenotypes for Cell 
Division Cycle (CDC) mutants, i.e. mutations which cause a cell cycle 
arrest phenotype. Here are some of the ones I worked on yesterday:

    CDC60   leucyl tRNA synthetase
    PRT1    Subunit of eIF3
    ALA1    alanyl-tRNA synthetase
    CDC65   mitochondrial tRNA-Glu
    SPT16   Subunit FACT transcription elongation complex

I don't think that anyone in the yeast community would expect or want to 
see any of these genes annotated to a GO process related to the cell 
cycle. There are lots of examples of where a mutant phenotype is due to 
some downstream effect and not due to the primary defect.

So, at SGD, we try to focus on the primary process. Obviously, we don't 
always know, but once we do, we like to avoid making GO annotations for 
processes that are known to be downstream, rather than direct, results of 
the mutation.

For Doug's specific example, if comparative data suggested that the gene 
was a specific regulatory transcription factor, I'd probably be inclined 
to go ahead and make specific process annotations. However, if comparative 
data suggested that it was related to a Pol II general transcription 
factor, I might not want to make a GO process annotation to such a 
specific process.

At all of the Annotation Camps, we've always said that one should be 
careful when making annotations from mutant phenotypes. At both of the 
public ones, the question has come up of how much to annotate from mutant 
phenotypes. The answer we've given has been that if one only has a mutant 
phenotype to annotated from, then make the best annotations you can. 
However, be aware that as you learn more, you may find that some of the 
mutant phenotypes are indirect results rather than something the gene 
product is directly involved in, and that in these cases you may choose to 
remove process annotations based on these phenotypes.

I think this is still good advice, that curator judgement should play a 
role in deciding whether a GO process annotation is merited from any 
particular mutant phenotype.

-Karen

On Sun, 6 Jul 2008, Judith Blake wrote:

> I can understand the duplication of effort, but since the GO and phenotype 
> annotations aren't co-mingled in GOdb, the SGD genes would I think appear 
> under-annotated if the effect of the gene on phenotype is not curated in BP. 
> For comparative genomics studies using GO, this would be missing, yet 
> available in the literature, information.
>
> for mouse, the phenotype data is effectively 'disfunction' data, so the 
> phenotype annotation reflects a different view from the GO annotation.
>
> Judy
>
> Julie Park wrote:
>> Hi Doug,
>> 
>> SGD's practice on this is that if it is known that what is being observed 
>> is a secondary/downstream effect, then we only capture it via phenotypes 
>> and not as a GO process.  However, if the gene product in question is not 
>> well characterized or there is a conflict in the literature about whether 
>> it is a direct or indirect involvement then we would give it a GO 
>> annotation.
>> 
>> We've made a decision to use GO to try and capture the primary role of a 
>> gene product as much as possible and to reduce the duplication of effort 
>> required to capture data both in GO and as phenotypes.
>> 
>> Just our take on things.
>> 
>> Regards,
>> -Julie
>> 
>> 
>> On Jul 3, 2008, at 3:16 PM, Doug howe wrote:
>> 
>>> Hi David,
>>> It still seems like there is a line that has to be drawn somewhere.
>>> We've talked in the past about the scope of a process...when does it
>>> start and when does it end?  A gene that has as it's primary role
>>> regulation of transcription (perhaps binds DNA etc. etc.) may have a
>>> secondary effect upon eye morphogenesis.  However, the process of eye
>>> morphogenesis does not start with the binding of such a gene to a
>>> regulatory sequence...it is a downstream consequence....and perhaps it
>>> is the gene who's expression is being regulated that is really involved
>>> in the downstream process.  It seems like there is a significant amount
>>> of redundant curation work to do if we always annotate both GO and
>>> phenotype using the same GO process terms.  I'm not strongly opposed to
>>> such annotations, I just want to revisit the discussion and see if
>>> anyone has other views on the issue.
>>> -Doug
>>> 
>>> David Hill wrote:
>>>> Doug,
>>>> 
>>>> I do this all the time. I just finished systematically doing all the 
>>>> homeobox genes in mouse. Many of them are annotated to things like 
>>>> pattern specification. I think in the future, it will be very nice to 
>>>> know these are playing roles in regulating transcription but that 
>>>> regulation is fundamental in other processes as well.
>>>> 
>>>> David
>>>> 
>>>> Doug howe wrote:
>>>>> I'm still struggling with the issue of whether to make a GO annotation 
>>>>> (processes in particular) or only phenotype annotation.  The zebrafish 
>>>>> literature is replete with mutant papers that often describe phenotypes 
>>>>> involving eyes, otic vesicles, or pharyngeal arches, organ development 
>>>>> etc.   Often, the IEA annotations for a gene seems to indicate that the 
>>>>> gene is binding DNA, and may be some sort of transcriptional regulator. 
>>>>> Should such a gene be annotated with GO terms like 'otic vesicle 
>>>>> development', or 'eye morphogenesis', or should that be left for 
>>>>> phenotype annotations?
>>>>> 
>>>> 
>>> 
>>> -- 
>>> Doug Howe, Ph.D.
>>> ZFIN Scientific Curator
>>> Zebrafish Nomenclature Coordinator
>>> 
>>> 
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