Category:RefGenome Electronic Jamboree 2010-02 SLIT2

See the talk page for discussion. See also Help:Annotation Jamborees

Orthoset

Ortholog set at PPOD

Participants

Annotations

Notes

Term Requests

Accepted:

1. NTR: smooth muscle cell chemotaxis GO:0071670 (SourceForge ID:2952208; Ruth)
2. NTR:regulation of smooth muscle cell chemotaxis GO:0071671
3. NTR:negative regulation of smooth muscle cell chemotaxis GO:0071672
4. NTR:positive regulation of smooth muscle cell chemotaxis GO:0071673
5. NTR:mononuclear cell migration GO:0071674 (SourceForge ID:952217; Ruth)
6. NTR:regulation of mononuclear cell migration GO:0071675
7. NTR:negative regulation of mononuclear cell migration GO:0071676
8. NTR:positive regulation of mononuclear cell migration GO:0071677
9. NTR:olfactory bulb axon guidance GO:0071678 (SourceForge ID: 2952671; Varsha)
10. NTR:commissural neuron axon guidance GO:0071679
11. NTR:Slit-Robo signaling complex GO:0071666 (SourceForge ID:2950516; Susan)
12. NTR: negative regulation of retinal ganglion cell axon guidance (SourceForge ID:2942137 [1]; Yasmin)
13. NTR: negative regulation of cellular response to growth factor (SourceForge ID:2952222; Ruth)
14. NTR: negative regulation of chemokine receptor expression (SourceForge ID:2952897; Varsha)-Rejected, David suggests making a dual annotation to negative regulation of gene expression (and using column 16) and the regulation of the signaling
15. Improving guidance and chemotaxis relationships (SourceForge ID:2952195&; Ruth)-fixed

Unresolved:

1. NTR: Roundabout receptor signaling pathway (SourceForge ID:2952646; Varsha)

• NTR: initiation of SLIT signal transduction
• NTR: termination of SLIT signal transduction

2. regulation of gene expression GO:0010468 (SourceForge ID:2952691; Varsha)

• Would it be possible to widen the name of the term GO:0010468 to include 'gene product'?
• i.e. GO:0010468 regulation of gene or gene product expression. We feel this would make it clear that the term is used for the regulation of all aspects of protein production as well as the regulation of mRNA production.

Annotation Queries

1. PMID:11748139 Paper shows that Slit causes chemorepulsion in vitro, but authors concerned about in vivo relevance. Should data from this be annotated? Annotate to chemorepulsion and then make a NOT annotation to the more specific term chemorepulsion olfactory bulb axons using this paper? (Rachael)

2. Is SLIT2 regulating axon guidance or involved in the process of axon guidance? SLIT2 negatively regulates axon migration and is a central part of axon guidance. Surely axon guidance is a regulatory pathway unlike axon migration (which can be random or directed) (Varsha).

3.'growth cone collapse' - is this negative regulation of axon guidance? If axon guidance is a regulatory process perhaps collapse should be a child of axon guidance; being part of the process of axon guidance. (Ruth) Anita Bandrowski has commented on this query, see below

Anita Bandrowski has commented on point 3 plus additional information

1.

• axon guidance should have two parts including "target selection" and "axon pathfinding" as these appear to be two processes that should not be confused
• axon guidance should be a broader term including brain wiring and growth cone guidance should be the narrower term including mainly molecular signaling, in the skos model sense
• positive and negative regulation of axon growth cone growth, and these should really be attraction and repulsion (as above)
• axon pruning - tends to be activity dependent, so it is not likely to be related to growth cones
• axon retraction - this is a term that also should be in context of a disease state as it is only visible in injury

2. (re point 3) growth cone collapse is not a physiological term as it has not been demonstrated in vivo, so it can be thought of in terms of an assay result. Growth cone collapse is a regulation term for axon guidance. Axon guidance can be thought of as being regulated mainly by the semaphorins, which are talked about as being the regulators of axon growth. In that process some semaphorins tell the growth cone to stop growing, i.e., collapse.

3. chemotaxis is the mechanism of signaling involved in migration. Ideally GO should have child terms for "axon guidance" representing the different types of 'chemotaxis' molecules

• secreted attractant (synonym: diffusable attractant, synonym: long-range attractant)
• contact-mediated attractant (synonym: non-diffusable attractant, synonym: short-range attractant)
• secreted repellent (synonym: diffusable repellent, synonym: long-range repellent) eg SLIT2
• contact-mediated repellent (synonym: non-diffusable repellent, synonym: short-range repellent)
• The main paper laying this out is PMID:8895455

4. It seems that you already have many axon guidance terms for individual cells. I am not sure why you would chose to innumerate these as opposed to composing these out of "axon guidance" of "any cell". Indeed you seem to have even gone down further into terms like 'corticospinal axon guidance through the internal capsule' giving the GO a lot of complexity. I presume that for the sake of completeness you would also need to precompose all regions that a corticospinal axon goes through as axon guidance happens from neuron birth until the axon is fully formed (from cortex to spine). It seems to me that this is cumbersome as every neuron in every species will have a certain tract that it will need to follow to get to its final destination and that would result in many children of axon guidance.

5. I have never understood how many logical restrictions are allowed on top of GO terms, but it may be a good idea here to say that there is a general process called axon guidance and any neuron that has an axon will undergo this process during development.

WB IMP Annotations

Some WB IMP annotations have apparently come from an error in the script that maps sequences used in RNAi experiments to the C. elegans genome. This results in annotations like the one to 'receptor-mediated endocytosis'. The script will be fixed and these annotations likely removed.

References

See Help:References for how to manage references in GONUTS.

Minutes

Present: Ruth Lovering; BHF-UCL, Anita Bandrowski; UCSD, Midori; GO editors, Rachael, Yasmin, Emily; UniProtKB-GOA, Mike Livstone; Princeton, Laskmi, Fiona; AgBase, Brenley, Texas A&M, Stan; RGD, Li; MGI, Ranjana, Kimberly; WormBase

Chair: Pascale

Minutes: Emily

Pascale; please could all groups ensure items are added to the agenda before the meeting.

Anita; SLIT2 is a diffusable chemotaxis factor that acts as a repellent involved in turning axons away from crossing the midline.

Midori; There is no outstanding issue for the creation of the Roundabout receptor signaling pathway terms, Rebecca Foulger will shortly be generating new signalling terms; so these requests are just waiting for Becky to become familiar with OBO-Edit.

Distinction between axon and neuron guidance

Midori; need input on chemotaxis and guidance. What is the distinction between neuron and axon guidance? Are axon guidance and chemotaxis are synonyms?

Anita; Unsure what neuron guidance would mean. GO should only need neuronal migration migration terms (could add neuron guidance is a synonym, although this term is seldom used by the research community). Axon guidance describes the part of the neuron that migrates elsewhere.

Growth Cone Collapse

Anita; there was also a question regarding ‘growth cone collapse’. Collapse does not happen in vivo; it only occurs as part of an in vitro assay that looks at the action of negative regulators. Midori; will add ‘growth cone collapse’ as a synonym of ‘negative regulation of axon guidance’ – and will note in the term’s comment section that collapse refers to observations from an in vitro assay.

Discussion regarding the term name: ‘regulation of gene expression’ GO:0010468 (SourceForge ID:2952691).

There were concerns that the full scope in the definition is not indicated in the name. A user would not expect the term to additionally include regulation of protein levels – couldn’t the term name be expanded?

Midori: No. ‘regulation of gene expression’ should remain, it is a well-recognised name that users would search for. Only willing to consider adding a synonym of ‘gene product expression’. No further changes will be made.

Annotation Query regarding questionable in vivo relevance.

Rachael: PMID:11748139 Paper shows that Slit causes chemorepulsion in vitro, but authors concerned about in vivo relevance. Should data from this be annotated? Annotate to chemorepulsion and then make a NOT annotation to the more specific term chemorepulsion olfactory bulb axons using this paper?

Anita; SLIT proteins are not simple chemotaxis agents; they are highly specific to certain axon guidance processes. Therefore I would tend to try to annotate to the more specific chemotaxis terms where possible. However it is difficult to make a judgement in this case. Will have a look at the paper. (Note from Rachael after call: Anita has looked at the paper and agreed that the annotations we should make are to GO:0007411 'axon guidance' and to NOT GO:0021834 'chemorepulsion involved in embryonic olfactory bulb interneuron migration')

Is SLIT2 regulating axon guidance or involved in the process of axon guidance?

SLIT2 negatively regulates axon migration and is a central part of axon guidance. Surely axon guidance is a regulatory pathway unlike axon migration (which can be random or directed). The current hierarchy does not show this term as a regulatory term, but isn’t it? Guidance is involved in providing positive/negative cues to migration.

Currently axon guidance is a child of cellular component movement – should axon guidance instead be underneath the regulation of cellular component movement.

Anita to look into and discuss further over sourceforge. (Note from Rachael after call: Further comments from Anita: "I have been thinking about axon guidance and the regulation thereof and while axon outgrowth can have a set of regulation terms associated, it seems that axon guidance is a term that already encompasses 'getting somewhere' as opposed to just axon outgrowth. I am sure that Barry Smith would have many things to say about this, but the term does not seem like a regulation of function, it is the regulated function.")

Anita; in addition should axon guidance have specific child terms to describe axon pathfinding and target selection. As pathfinding is a separate chemical process – involving semaphorins, where diffusable negative/positive signals are specifically used. Whereas target selection is specific to ensuring specific outgrowths from certain cells –and involves more non-diffusible messages – GO does not have a term for this – but would be a part of axon guidance.

Anita; currently axon guidance is a child of cellular component movement – should axon guidance instead be underneath the regulation of cellular component movement. Pascale; the defintion of regulation terms is difficult in GO.

Use of the IEP evidence Code

Fiona; chicken papers often look at the expression of the gene in certain tissues over time, and curators are wondering whether based on this expression profile to make an IEP annotation. However how do curators feel about making an inference based on an mRNA profile, rather than a protein level profile?

Pascale; this is a reasonable annotation to make as the IEP code is there specifically indicates that evidence for the association has been obtained from expression profiles.

Fiona: We’d only be annotating using process/high level terms.

Mike; if expression levels do change – even if only mRNA then could assume that protein levels will be changing also

Other curators; well there often are differences in mRNA and protein profiles.

Susan/Pascale: if your gene had very little data, then you could include this information, even if only obtained from mRNA expression levels – if however you have more information on gene function then we’d exclude such evidence. Caution by the curator is implied via using the IEP level.

Li: database specific issue. MGI does not use IEP at all.

GO NUTs wiki - Improvements

Jim: did any curator find the filter boxes useful? There are now filters on gene pages and the GO summary.

Dianna, Emily; Yes, found this useful for reviewing annotation sets.

Emily – New feature request: filtering options be remembered? I needed to repeatedly use the filters after I had carried out any edit on an annotation table. Could my filtering/sorting set up be remembered between edit actions?

Jim; this might be possible – will look into

Rachael; had tested a beta version of the bulk upload facility that Daniel had generated, which would mean that GAF-formated bulk uploads could be made. Rachael had problems with this facility. Rachael and Jim to talk about further.

Pascale: GO camp. Could curators please fill in the page listing annotation issues, available at:

http://wiki.geneontology.org/index.php/2010_GO_camp_Meeting_Logistics#Suggestions_for_annotation_issues_to_be_discussed