Signaling Meeting Minutes November 2009

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November 4th 2009

Plan for changes to be made. Preferably able to be completed and made live before March 1st 2009.

Participants: Sandra Orchard, Alex Diehl, Peter D'Eustachio, Jennifer Deegan.

Discussion

We discussed how best to do some really concrete work that can be committed before next March, that will pave the way for future work, but without requiring super-human effort to finish in time.

We all agreed that we have been circling round the same problems with the top terms for some time now. Peter suggested that we should each take a pathway that we are very familiar with and try to put the terms in around the new structure that we have created. Everybody agrees that this is a good idea. It will test the structure we have already, and if we can get some pathways right then they will serve as good examples to be followed in future editing by others.

Everybody is able to to use OBO-Edit at least for browsing the file. Jennifer will send the link to the file and people can either edit the file directly in OBO-Edit or put their new structure up on this wiki page.

Jennifer will also make a doodle poll to set up a meeting for three weeks from now, to discuss what we have done.


Instructions

File

http://cvsweb.geneontology.org/cgi-bin/cvsweb.cgi/go/scratch/signaling3.obo

CVS version number

If you are going to edit the file in OBO-Edit, please could you note down the cvs version number of the file that you started with, as this will be required for merging the changes in again.

OBO-Edit

This is the place to go to get OBO-Edit: https://sourceforge.net/projects/geneontology/files/

Number range

If you would like to make new terms you will need to set up a new number range. It will be best to number terms from 1-999 and have a prefix corresponding to your initials, so for example my first term would be JID:0000001.

To set a number range you go to the menu 'Metadata' then choose 'ID Manager' and then you click the little cog icon and put this in the box: GO:$sequence(7,0000001,0000999)$
You only need to change 'GO' to your initials.

24th November, 2009

Participants: Ruth Lovering, Alex Diehl, Jennifer Deegan, Stan Lauderkind.

We decided to work on the dopamine pathway during this meeting.

The dopamine pathway

Action: Jen to write to Erika Feltrin and ask if she has time to look over what we have done. (DONE - no response yet)

We took the parts of the dopamine pathway in chronological order and slotted the various processes in.

Dopamine secretion

pre-existing structures:

[i]secretion by cell
---[i]catecholamine secreton
------[i]dopamine secretion (pre-existing term)

[i]dopamine transport
---[i]dopamine secretion

new structure:

[i]signaling
---[p]signaling process
------[i]signal transmission
---------[i]signal release
------------[i]dopamine secretion 

Activation step

New:

[i]dopamine receptor signaling pathway
---[pr]positive regulation of dopamine receptor signaling pathway
------[i]activation of dopamine receptor signaling pathway

[i]signaling process
---[i]initiation of signal transduction
------[i]signal initiation by diffusable mediator
---------[i]signal initiation by neurotransmitter
------------[i]activation of dopamine receptor signaling pathway

We noted that the structure above could be most correctly set up with reference to ChEBI.

Signal transduction step

Moved to cell surface receptor linked signal transduction.

[i]signaling
---[i]signaling pathways
------[i]cell surface receptor linked signal transduction
---------[i]G-protein coupled receptor protein signaling pathway
------------[i]dopamine receptor signaling pathway

Termination step

For this we looked at the pre-existing term "activation of adenylate cyclase activity by dopamine receptor signaling pathway"

Pre-existing:

---[i]dopamine receptor signaling pathway
------[i]activation of adenylate cyclase activity by dopamine receptor signaling pathway 

New:

[i]signaling
---[p]signaling process
------[i]signal transmission
---------[i]conclusion of signal transduction (renamed from signal termination)
------------[i]activation of adenylate cyclase activity by dopamine receptor signaling pathway

Questions: Each pathway may have many many different effects, and each of these could be counted as a type of "conclusion of signal transduction". Should we even by trying to capture these as termination steps? Will it lead to a massive explosion in the graph?

30th November, 2009

Participants: Sandra Orchard, Peter D'Eustachio, Jennifer Deegan, Susan Tweedie, Ruth Lovering.

We discussed whether this is correct:

[i]conclusion of signal transduction (renamed from signal termination)
---[i]activation of adenylate cyclase activity by dopamine receptor signaling pathway

and how we might connect the child term to adenylate cyclase activity and to the effects further downstream. We were not clear on whether the term should be connected to the dopamine signaling at all. We considered asking the GO list for feedback.

There was a general feeling that users should be able to trace the process through from signal to effect using the ontology (or ontologies). However we were not sure of the downstream effects of dopamine, which made it difficult to determine how to do this. To deal with this we switched topic to T cells, since Sandra was present and knows T cell signaling in great detail.

We started to make terms for T cell signaling, but then realised that it might make more sense for the editing work to be done during the week with only Jennifer and Sandra present. This will be done before next week so we can look at the effects of T cell signaling then with everybody present to discuss it.

2nd December

Participants: Sandra Orchard, Jennifer Deegan

Sandra Orchard has expert knowledge of T cell signaling so we worked on making terms to describe this pathway.

Here are the edits we made:

Added inititation terms:

Tcellinitiation.jpg

"Signaling via conformational transition" moved to be child of "signal transmission" and then renamed "signal transmission via conformational transition".

We made a new term "signal transmission via an intracellular cascade" and put pre-existing "protein kinase cascade" underneath.

New and rearranged transmission terms:

Tcelltransmission.jpg

We made a new term "signal transmission via a phosphorylation event" plus cis- and trans- children.

We made "signal transmission via diffusible molecule" and "T cell activation signal transmission via diffusible molecule".

Under "MAPKKK cascade" the existing terms are muddling terminology and we should be using human genome nomenclature. e.g. instead of JNK we should use MAPK8, MAPK9, MAPK10. The Human Genome group do not use the MAPKKK terminology either, they use MEK instead of MAPKKK. We need to standardise to their system. Jennifer gave Sandra a list of the names of terms that are descendents of MAPKKK and she will list the correct names to be edited in. (For list, see below)

"conclusion of signal transmission" renamed to "consequence of signal transmission"

New terms: "regulation of gene expression as a consequence of signal transmission" and "regulation of gene expression as a consequence of T cell signal transmission". "Regulation of gene expression as a consequence of signal transmission" made is_a to "regulation of gene expression".

New term: "termination of T cell signal transduction" added under "termination of signal transduction", which is under "signaling process".


Descendents of MAPKKK cascade

GO:0007256	activation of JNKK activity
GO:0042655	activation of JNKKK activity
GO:0007257	activation of JUN kinase activity
GO:0000187	activation of MAPK activity
GO:0000199	activation of MAPK activity during cell wall biogenesis
GO:0000169	activation of MAPK activity involved in osmosensory signaling pathway
GO:0000186	activation of MAPKK activity
GO:0000198	activation of MAPKK activity during cell wall biogenesis
GO:0000168	activation of MAPKK activity involved in osmosensory signaling pathway
GO:0000185	activation of MAPKKK activity
GO:0000197	activation of MAPKKK activity during cell wall biogenesis
GO:0000167	activation of MAPKKK activity involved in osmosensory signaling pathway
GO:0070375	BMK cascade
GO:0070371	ERK1 and ERK2 cascade
GO:0000188	inactivation of MAPK activity
GO:0000200	inactivation of MAPK activity during cell wall biogenesis
GO:0000173	inactivation of MAPK activity involved in osmosensory signaling pathway
GO:0051389	inactivation of MAPKK activity
GO:0051390	inactivation of MAPKKK activity
GO:0007254	JNK cascade
GO:0007258	JUN phosphorylation
GO:0000196	MAPKKK cascade during cell wall biogenesis
GO:0000161	MAPKKK cascade involved in osmosensory signaling pathway
GO:0070377	negative regulation of BMK cascade
GO:0070373	negative regulation of ERK1 and ERK2 cascade
GO:0046329	negative regulation of JNK cascade
GO:0043409	negative regulation of MAPKKK cascade
GO:0032873	negative regulation of stress-activated MAPK cascade
GO:0000189	nuclear translocation of MAPK
GO:0000201	nuclear translocation of MAPK during cell wall biogenesis
GO:0000208	nuclear translocation of MAPK involved in osmosensory signaling pathway
GO:0070378	positive regulation of BMK cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0046330	positive regulation of JNK cascade
GO:0043410	positive regulation of MAPKKK cascade
GO:0032874	positive regulation of stress-activated MAPK cascade
GO:0070376	regulation of BMK cascade
GO:0070372	regulation of ERK1 and ERK2 cascade
GO:0046328	regulation of JNK cascade
GO:0043408	regulation of MAPKKK cascade
GO:0032872	regulation of stress-activated MAPK cascade
GO:0051403	stress-activated MAPK cascade

The changes will best be seen by looking at the file (version 1.18), which is at:

http://cvsweb.geneontology.org/cgi-bin/cvsweb.cgi/go/scratch/signaling3.obo

To see the exact edits in a colored diff see:

http://cvsweb.geneontology.org/cgi-bin/cvsweb.cgi/go/scratch/signaling3.obo.diff?r1=1.17;r2=1.18;f=h

2nd December

Participants: Erika Feltrin, Jennifer Deegan

Erika's comments on our dopamine terms:

"activation of dopamine receptor signaling pathway" needs a very precise definition because there are different kinds of dopamine receptor. One family is excitatory and one is inhibitory, and both are coupled to G-protein. One binds G-protein alpha s and one binds G-protein alpha i. This is shown in Reactome. There are two reactions for each binding event. See REACT 17033.1 (excitatory) and REACT 16959.1 (inhibitory).

Explanation of the process:

Dopamine crosses the synapse and binds the dopamine receptor. Then the receptor is coupled with G-proteins. Next G-protein kicks off the signaling pathway inside the cell. There are several different signals. The signals convert ATP to cAMP. cAMP activates kinases, and then there are other changes in the channels that allow movement of neurotransmitters in the cell.

For the term: activation of adenylate cyclase by dopamine: when you activate adenylate cyclase you generate a lot of signal transduction. Adenylate cyclase is everywhere in the cell so this is a very general activation and not at all specific to dopamine.

G-protein signaling is the same. The signal starts from G-protein but is activated by dopamine. The G-protein signaling is a very general process and is not specific to dopamine activated G-protein signaling. However, dopamine is one of the molecules that can activate G-protein signaling.

Look also in ChEBI (CHEBI:18243) and ask the reactome people for their advice.

Erika was not able to fill us in on what happens further downstream from dopamine, though she thought that people at GlaxoSmithCline would know. She is no longer active on this project so could not liaise between GO and GSK on it.