[Annotation] phenotype or GO-still struggling
Judith Blake
jblake at informatics.jax.org
Tue Jul 15 12:38:32 PDT 2008
I'm sorry if I said or implied that all phenotype evidence should be
annotated with GO. I think I was responding to the idea that SGD was
*not* using IMP or phenotype data because of lack of specificity. MGD
has LOTS of phenotypic experimental data, and certainly not even a tiny
bit is reflected in a GO annotation. A given paper may result in 10 MP
(mammalian phenotype ontology ) term assignments, and one, maybe two
rather high-level IMP GO annotation. But if the GO annotations were
missing, folks looking at data analysis using the GO would miss that
connection also. I only suggest that IMP annotations are useful.
Judy
Biological Process regulation of long-term neuronal synaptic plasticity
<http://www.informatics.jax.org/searches/GO.cgi?id=GO:0048169> IMP
MGI:1928283
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283>|MGI:1928284
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928284>
J:62289 <http://www.informatics.jax.org/searches/reference.cgi?63233>
Biological Process adult locomotory behavior
<http://www.informatics.jax.org/searches/GO.cgi?id=GO:0008344> IMP
MGI:1928283
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283>|MGI:1928284
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928284>
J:62289 <http://www.informatics.jax.org/searches/reference.cgi?63233>
Biological Process startle response
<http://www.informatics.jax.org/searches/GO.cgi?id=GO:0001964> IMP
MGI:1928283
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283>|MGI:1928284
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928284>
J:62289 <http://www.informatics.jax.org/searches/reference.cgi?63233>
http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=markerGO&key=9271
the J:62289 links to the PubMed Abstract
vs
Allele Symbol: Grin1^tm1Blt
Name: targeted mutation 1, Horst Bluethmann
ID: MGI:1928283
Synonyms Grin1^D481N , Grin1^tm1Jnck
Allele details
Allele Type: Targeted (knock-in)
Strain of Origin: 129P2/OlaHsd
ES Cell Line: E14
Mutation: Disruption caused by insertion of vector
Point mutations were introduced by homologous recombination which
altered the sequence corresponding to codon 481 from aspartic acid
to asparagine. A loxP flanked neomycin/thymidine kinase cassette in
intron 10 was removed by transient Cre recombinase expression,
leaving one loxP site in the intron. (/J:62289
<http://www.informatics.jax.org/searches/reference.cgi?63233>/)
International Mouse Strain Resource: (Search for IMSR strains
<http://www.informatics.jax.org/imsr/fetch?page=imsrSummary&op:gsymname=%3D&gsymname=Grin1&gsymnameBreadth=C>
with Grin1 mutations)
References and Additional Notes: (See Below
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283#Additional_Info>)
Gene
information Symbol: Grin1
<http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=markerDetail&key=9271>
Name: glutamate receptor, ionotropic, NMDA1 (zeta 1)
Chromosome: 2
Genetic Position: 12.0 cM
Genome Coordinates: Chr2:25146701-25174707 bp, - strand (From VEGA
annotation of NCBI Build 37)
Human Ortholog: GRIN1
<http://www.informatics.jax.org/searches/homology_report.cgi?_Marker_key=21602>
Phenotypes
Phenotypic details for all genotypes that include at least one
Grin1^tm1Blt allele
Allelic Composition Genetic Background
Grin1^tm1Blt
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283>/Grin1^tm1Blt
<http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1928283>
involves: 129P2/OlaHsd * C57BL/6
behavior/neurological
abnormal spatial learning
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001463>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* acquisition of a task in a water maze is impaired, with
significantly lower escape latencies, however they achieve a
similar final level of performance as controls
increased startle reflex
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001488>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* significantly higher startle response to 90 and 110 dB and a
lower threshold for startle reactivity
impaired coordination
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001405>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* impaired motor coordination in hanging wire test, with
homozygotes unable to lift hindpaws onto the wire
* reduced activity in horiontal open field test
abnormal locomotor activity
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001392>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* spend significantly more time in the center of a cage than
controls
resistance to pharmacologically induced seizures
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0002887>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* less sensitive to intracerebroventricular NMDA-induced convulsions
nervous system
abnormal nervous system physiology
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0003633>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* exhibit reduced NMDA receptor glycine affinity, but not
glutamate affinity, and do not have any gross CNS abnormalities
resistance to pharmacologically induced seizures
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0002887>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* less sensitive to intracerebroventricular NMDA-induced
convulsions
reduced long term potentiation
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001473>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* exhibit a deficit in hippocampal theta burst-induced LTP
hearing/vestibular/ear
increased startle reflex
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0001488>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* significantly higher startle response to 90 and 110 dB and a
lower threshold for startle reactivity
homeostasis/metabolism
resistance to pharmacologically induced seizures
<http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0002887>
(/J:62289/
<http://www.informatics.jax.org/searches/reference.cgi?63233>)
* less sensitive to intracerebroventricular NMDA-induced convulsions
Karen Christie wrote:
> There's a big difference between saying some GO annotations with IMP
> evidence are valid and that all IMP evidence should be annotated in GO.
>
> -Karen
>
> On Tue, 15 Jul 2008, Judith Blake wrote:
>
>> Frankly I don't understand why we are having this discussion when we
>> agree that IMPs are valid annotations. Of course one might
>> re-evaluate IMPs with new data. I don't understand why this is big
>> news.
>>
>> Judy
>>
>> Karen Christie wrote:
>>> Hi,
>>>
>>> I completely agree with what Val said, including that in both Judy's
>>> and Harold's examples, I agree that it is appropriate to make
>>> annotations based on current knowledge.
>>>
>>> I also sometimes come across genes where there is evidence that
>>> shows/suggests that it has multiple roles. Most recently REX2, which
>>> is involved in 3'-end processing of various different
>>> nuclear/nucleolar RNAs, and is also localized to the mitochondrion
>>> where its role is not clear but it interacts genetically with TRZ1,
>>> the tRNA 3'-end processing endonuclease. In cases like these, we
>>> make all the annotations that are supported by experimental
>>> evidence, even those that may be surprising.
>>>
>>> However, much more frequently, I come across cases where the
>>> original idea about what a gene did, based solely on its mutant
>>> phenotype, is later shown to be due to a downstream effect of the
>>> mutation or to an artifact of the experimental system. In these
>>> types of cases, we choose not to represent these mutant phenotypes
>>> as GO annotations. Some examples of known cases for cerevisiae are
>>> below.
>>>
>>> So, as more is known about a given gene, it seems it is often
>>> appropriate to reevaluate whether old annotations based on IMP are
>>> still valid. Sometimes they are and other times they really seem
>>> inappropriate in light of new knowledge. For multicellular
>>> organisms, many of these developmental mutants may well turn out to
>>> be genes specifically involved in that developmental process. I went
>>> to a talk a couple months ago that said that mammals have 100-1000
>>> fold more specific regulatory transcription factors than yeast. A
>>> mutant in one of these might be quite informative as to which
>>> processes it regulates.
>>>
>>> However, there will surely also be cases where there is something
>>> else is occurring. For example, a human disease called SCID (Severe
>>> Combined Immune Deficiency) is caused by deficiency of the enzyme
>>> adenosine deaminase (ADA). However, I'm not sure one would want to
>>> say that ADA is involved in immune cell development; it is generally
>>> active through the body. Rather, when ADA is defective, a toxic
>>> intermediate builds up and immune and other rapidly dividing cells
>>> are most sensitive. As the specific effect of ADA mutantions on
>>> immune cells is a pathology, rather than a normal process, it seems
>>> outwith the scope of GO to annotate the immune cell effect of ADA
>>> mutants.
>>>
>>> SGD has also started having large sets of high-throughput mutant
>>> phenotypes data. We have found that many of these screens identify
>>> large sets of genes with a given phenotype. However, based on the
>>> knowledge of what many of these genes do, we have become rather
>>> leary of making GO annotations wholesale from these large mutant
>>> phenotype studies because the mutant phenotype doesn't seem to be a
>>> very specific indicator of the process the gene is involved in.
>>> We're seeing a lot of these now. We've basically decided that though
>>> we are quite happy to put these into our phenotype curation
>>> wholesale, we are not comfortable in making GO annotations based on
>>> these large scale phenotype screens.
>>>
>>> -Karen
>>>
>>> Some specific examples for cerevisiae:
>>>
>>> 1. cell cycle arrest phenotypes: people looked for things with cell
>>> division cycle (cdc) arrest phenotypes in order to find cell cycle
>>> regulators. Some cdc mutants actually are cell cycle regulators.
>>> However,
>>> the collection of cdc mutants also includes:
>>> - tRNAs
>>> - tRNA synthetases
>>> - an Hsp90 co-chaperone
>>> - general transcription regulators, e.g. components of the Paf1
>>> transcription regulatory complex, members of the CCR4/NOT
>>> complex
>>> - things involved in response to mating pheromone (which do cause G1
>>> arrest, but which are not thought to be cell cycle regulators)
>>> - eIF4E cytoplasmic mRNA cap binding protein required for translation
>>>
>>> Inhibition of ribosome synthesis can also produce cell cycle arrest. A
>>> couple different U3 snoRNA associated complexes involved in the first
>>> stages of rRNA processing and small ribosomal subunit assembly have
>>> recently been characterized in yeast. U3 and many, if not most, of the
>>> proteins are conserved. Depeleting for most of the individual protein
>>> components of these complexes produces cell cycle arrest.
>>>
>>> So, while SGD would be quite happy to have a cell cycle arrest
>>> -phenotype-
>>> annotated for every gene, we don't really want to go on and make a GO
>>> process annotation to cell cycle for many of these genes.
>>>
>>> 2. splicing vs translation - A lot of things that turn out to be
>>> involved in splicing of nuclear mRNAs were originally characterized
>>> as being involved in translation. This turns out to be due to the
>>> unusual distribution of introns in S. cerevisiae. Only about 270
>>> genes, out of 6000, contain introns, and these are predominantly
>>> found in protein coding genes. Thus splicing defects have a very
>>> immediate effect on translation due to loss of production of
>>> ribosomal proteins.
>>>
>>> In light of the knowledge of why splicing mutants cause translation
>>> defects, we don't want to make GO process annotations to
>>> translation-related terms for splicing genes even if they do produce
>>> a translation-specific phenotype.
>>>
>>> 3. AAR2 - This gene was originally thought to be specifically
>>> required for splicing of MATa1 mRNA because mutant extracts appeared
>>> specifically defective in splicing this mRNA. It turns out to be due
>>> to the fact that MATa1 has 2 introns, while almost all other genes
>>> only have 1, which meant that the assay system ran out of splicing
>>> components when MATa1 was used, but not when any of the other test
>>> pre-mRNAs were used. There was actually a specific GO term
>>> (GO:0006377 - MATa1 (A1) pre-mRNA splicing) based on the original
>>> mutant characterization of this gene.
>>>
>>> It turns out that Aar2 is actually part of general splicing factor U5
>>> snRNP, and thus required for splicing generally. GO:0006377 was
>>> obsoleted
>>> because a MATa1-specific splicing process does not occur.
>>>
>>>
>>>
>>> On Fri, 11 Jul 2008, Valerie Wood wrote:
>>>
>>>>
>>>> Hi Judy/ Harold,
>>>>
>>>> In both of these examples (your heart development in the power
>>>> point, and Harolds ribosomal example), we would make these
>>>> annotations using current practices (so I don't think we are being
>>>> inconsistent here). I have a similar example to Harolds where a
>>>> subunit of RNA polymerase II plays a specialized role in cell
>>>> separation. This is what the data shows and this is fine.
>>>>
>>>> What Karen and I are saying is that not EVERY annotation which can
>>>> be made from a phenotype deserves a process annotation in the
>>>> context of all of the available information.
>>>>
>>>> Some processes which initially appear to be due to a particular
>>>> phenotype turn out to be downstream effects based on subsequent
>>>> information. We feel in these cases, where the effect is *known* to
>>>> be *indirect* effect of an upstream process, then the process
>>>> annotation based on this phenotype should be removed. It seems
>>>> increasingly that it is not helpful for our communities using GO to
>>>> make every annotation for the phenotype, if they are subsequently
>>>> shown to be a result of an upstream process. This is the feedback I
>>>> have got from my community, and makes more sense of global analysis.
>>>>
>>>> Sometimes the observations initially attributed to cell division
>>>> defects are actually known to be due to defects in DNA repair or
>>>> replication because replication is late and cytokinesis too early
>>>> cell division is compromised. There are many more dependencies on
>>>> rRNA processing and translation.
>>>>
>>>> If it is NOT clear (reported) that the phenotype is due to the
>>>> upstream process, then the IMP process from phenotype would still
>>>> be valid.This shows a different level of knowledge which can be
>>>> captured by a curator when more information is available. The
>>>> phenotypes in these cases are still captured as appropriate.
>>>>
>>>> Probably we have more cases like this because yeast are better
>>>> studied, and there are many dependencies in cell biology. SGD may
>>>> have some better examples as they have more legacy data.
>>>>
>>>> Val
>>>>
>>>>
>>>>
>>>>
>>>>
>>>> Judith Blake wrote:
>>>>> Hi,
>>>>> I sent a response with ppt and it's waiting to be moderated
>>>>>
>>>>> J
>>>>>
>>>>> Harold Drabkin wrote:
>>>>>>
>>>>>> On the other hand, we have to be careful about applying what we
>>>>>> think we know to ignore what a mutant phenotypes is telling you,
>>>>>> because things can be complicated. .I just finished looking at
>>>>>> one of the ribosomal proteins, Rpl10. There is very little mouse
>>>>>> data, but from skimming some other references (human), it appears
>>>>>> to be originally identified in a screen for tumor suppressors. It
>>>>>> is unclear why. It appears to be a protein that associates with
>>>>>> the large subunit after the subunit is exported from the
>>>>>> nucleus. However, there is some reference to it's release from
>>>>>> the 60S ribosomal subunit as a mechanism of transcript-specific
>>>>>> translational control. This might have been reflected in the
>>>>>> search for tumor suppressors. Yet another paper describes it is a
>>>>>> zinc-binding transcription regulatory protein: which can bind to
>>>>>> c-Jun i ( this binding is dependent upon zinc ions and
>>>>>> phosphorylation by protein kinase C ). Haven't looked at those
>>>>>> papers in detail; But there is something interesting going on
>>>>>> (no one has done a KO in mouse that I can find which might tell
>>>>>> us a bit more), and I'm not at all sure one should rule out that
>>>>>> it participates in other processes other than the one obvious
>>>>>> from it's name. Just grist for the mill.
>>>>>>
>>>>>> h
>>>>>>
>>>>>>
>>>>>> Valerie Wood wrote:
>>>>>>> I agree completely with Karen/SGD and this has been the
>>>>>>> procedure I have always followed.
>>>>>>> In the absence of any other information, a mutant phenotype is
>>>>>>> frequently used to infer a specific process. Once more
>>>>>>> information is available it often becomes clear that this is a
>>>>>>> downstream (indirect affect).
>>>>>>> For example defects in ribosome biogenesis and translation and
>>>>>>> general translation will often have plieotrophic affects which
>>>>>>> are indirect, as it will affect nearly every process downstream
>>>>>>> (for example there are associated downstream effects in
>>>>>>> chromosome segregation, cell division, and in multicellular
>>>>>>> organisms, multiple developmental processes). This does not
>>>>>>> mean that a biologist would expect to see the annotations to
>>>>>>> these processes once the upstream process is known. If we did
>>>>>>> follow this logic, then we would find that all genes involved in
>>>>>>> translation, ribosome biogenesis and general replication would
>>>>>>> eventually become annotated to most other processes.
>>>>>>>
>>>>>>> Another classic example from yeast is vacuolar targeting. Many
>>>>>>> mutants result in defects which result in proteins usually
>>>>>>> localized to the vacuole becoming mislocalised and were
>>>>>>> initially interpreted as a defect in protein targeting. It has
>>>>>>> since become clear that many of these defects are very far
>>>>>>> upstream of the vacuolar targeting pathway, and this is just a
>>>>>>> downstream consequence of things being mis folded, mis
>>>>>>> transcribed etc. Subsequently these annotations have gradually
>>>>>>> been removed as better information has become available.
>>>>>>>
>>>>>>> On the other hand, mutations in a gene may have phenotypic
>>>>>>> effects which you DO want to capture as processes (for example
>>>>>>> the effects of phenylalanine hydroxylase on skin pigmentation
>>>>>>> etc). However you would not necessarily want to curate the
>>>>>>> effect of a gene involved in all translation initation in a
>>>>>>> developmental process from a high throughput screen (once better
>>>>>>> information was avaiable). In Doug's example I would also follow
>>>>>>> Karen's suggestion and make the annotation if this is possibly
>>>>>>> specific transcription for the pathway (i.e specific to a subset
>>>>>>> of genes), but if the defect is definately general transcription
>>>>>>> I would not make the annotation.
>>>>>>>
>>>>>>> Not caputuring EVERY phenotype using biological process should
>>>>>>> not be considered underannotation. The purpose of GO process
>>>>>>> annotations is to capture processes not phenotypes. Sometimes
>>>>>>> phenotypes are direct indicators of the process a gene is
>>>>>>> involved in sometimes they are not.
>>>>>>> A major consequence of making these ubiquitous annotations is
>>>>>>> that can distort genome wide analysis (not improve it), and
>>>>>>> this is often the case when annotations come from high
>>>>>>> throughput screens and early experiments. Over the past couple
>>>>>>> of years cerevisiae and pombe have done a lot of 'tidying' of
>>>>>>> these legacy annotations, and the genome-wide GO data is much
>>>>>>> improved and useful as a result.
>>>>>>>
>>>>>>> This is also why annotations to orthologs made using ISS should
>>>>>>> only be made by a curator on a gene by gene basis and not by an
>>>>>>> automated process. A curator is able to assess all of the
>>>>>>> available information to make an ISS annotation (from different
>>>>>>> organisms) and distinguish between current annotations and
>>>>>>> legacy annotations.
>>>>>>>
>>>>>>> One way to distinguish these is whether the targets are generic
>>>>>>> (i.e every gene ) or specific (a subset of genes). If the genes
>>>>>>> targets are a subset of genes then the annotations is probably
>>>>>>> valid.
>>>>>>>
>>>>>>> Val
>>>>>>>
>>>>>>> Karen Christie <kchris at genome.stanford.edu> wrote:
>>>>>>>> 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
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>> _______________________________________________
>>>>>>>>>>> Annotation mailing list
>>>>>>>>>>> Annotation at geneontology.org
>>>>>>>>>>> http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>>>>>>>
>>>>>>>>>> _______________________________________________
>>>>>>>>>> Annotation mailing list
>>>>>>>>>> Annotation at geneontology.org
>>>>>>>>>> http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>>>>>>
>>>>>>>>> _______________________________________________
>>>>>>>>> Annotation mailing list
>>>>>>>>> Annotation at geneontology.org
>>>>>>>>> http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>>>>>
>>>>>>>>>
>>>>>>>> _______________________________________________
>>>>>>>> Annotation mailing list
>>>>>>>> Annotation at geneontology.org
>>>>>>>> http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>> ------------------------------------------------------------------------
>>>>>>> _______________________________________________
>>>>>>> Annotation mailing list
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>>>>>>>
>>>>>>
>>>>>> _______________________________________________
>>>>>> Annotation mailing list
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>>>>>> http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>
>>>>
>>>> --
>>>>
>>>> ---------------------------------------------------------------------------
>>>> Valerie Wood Tel: 01223 496909
>>>> S. pombe Genome Project Fax: 01223 494919 Wellcome Trust
>>>> Sanger Institute email: val at sanger.ac.uk
>>>> Wellcome Trust Genome Campus http://www.genedb.org/genedb/pombe
>>>> Hinxton, Cambridge, CB10 1HH
>>>> http://www.sanger.ac.uk/Projects/S_pombe
>>>>
>>>>
>>>>
>>>> --
>>>> The Wellcome Trust Sanger Institute is operated by Genome Research
>>>> Limited, a charity registered in England with number 1021457 and a
>>>> company registered in England with number 2742969, whose registered
>>>> office is 215 Euston Road, London, NW1 2BE.
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>>>>
>>
>>
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