Difference between revisions of "Annotation Conf. Call 2016-07-26"

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(Revised Protein Binding Documentation)
(LEGO Model for FlyBase Annotation Consistency Exercise Paper)
 
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*October 25 - RGD
 
*October 25 - RGD
 
*November 22 - Zfin
 
*November 22 - Zfin
*If you have thoughts about the exercises, please send them along to David and Kimberly.  At the end of the year, we will evaluate how this is working and if we need to make any changes to the format to keep these exercises useful for people.
+
*If you have thoughts about the exercises, please send them along to David and Kimberly.  At the end of the year, we will again evaluate how this is working and if we need to make any changes to the format to keep these exercises useful for people.
  
 
==Revised Protein Binding Documentation==
 
==Revised Protein Binding Documentation==
Line 27: Line 27:
 
   process.  Protein-protein interactions for which there is not yet sufficient biological context are discouraged as sources of GO MF  
 
   process.  Protein-protein interactions for which there is not yet sufficient biological context are discouraged as sources of GO MF  
 
   annotations.
 
   annotations.
*We also discussed, on the last conference call, the criteria by which protein binding annotations from IntAct are exported to GO.  A response from Sandra Orchard is on the [http://wiki.geneontology.org/index.php/Annotation_Conf._Call_2016-06-28#Protein_Binding_Documentation 2016-06-28 minutes].
+
*Also, the [http://geneontology.org/faq/how-are-binary-interactions-curated-intact-group-selected-export-go-protein-binding-go0005515 GO FAQs] have been updated to document how protein-protein interactions curated by IntAct are exported to GO as protein binding (GO:0005515) annotations.
*A summary:
 
  * Only experimental data is used for making the decision to export the protein pair to UniProtKB/GOA as a true binary interacting pair
 
  * The export decision is always based on at least two pieces of experimental data. A single evidence cannot score highly enough to
 
  trigger an export
 
  * An export cannot be triggered if the protein pair only ever co-occurs in larger complexes, there must be at least one evidence that
 
  the proteins are probably in physical contact.
 
  
 
==Questions about Membrane Cellular Component Annotations==
 
==Questions about Membrane Cellular Component Annotations==
 +
*This annotation issue was raised by Rebecca and concerns annotation to membrane child terms, e.g. integral to synaptic vesicle membrane, given different types of experimental results.
 
*We will resume discussion of this issue when Rebecca is back.
 
*We will resume discussion of this issue when Rebecca is back.
*In the meantime, there is a summary from Rebecca on the 2016-07-11 minutes.   
+
*In the meantime, there is a [http://wiki.geneontology.org/index.php/Annotation_Conf._Call_2016-07-11#Questions_about_Membrane_Cellular_Component_Annotations_2 nice summary] from Rebecca on the 2016-07-11 minutes.   
*Please take a look and review the discussion and proposal so we can move towards finalizing our decision on the 2016-08-09 call.
+
*Please take a look and review the discussion and proposal so we can move towards creating guidelines on the 2016-08-09 call.
  
 
==LEGO Model for FlyBase Annotation Consistency Exercise Paper==
 
==LEGO Model for FlyBase Annotation Consistency Exercise Paper==
 +
*Review annotations to [http://www.ncbi.nlm.nih.gov/pubmed/27146270 paper on memory] and relations between them in [http://noctua.berkeleybop.org/editor/graph/gomodel:5745387b00001247 LEGO model]
 +
*Review resulting GAF (from Model drop-down menu, select Export GAF)
 +
*Review additional annotations desired from a GAF output.
 +
*Review use of directly_inhibits relation between acetylcholine transporter and receptor activities in LEGO model and annotation to inhibitor activity based on the definition.
 +
*Compare with [http://wiki.geneontology.org/index.php/Annotation_Conf._Call_2016-06-28#Annotation_Consistency_Exercise annotations submitted from consistency exercise]
 +
*<span style="color:green">GREEN = Noctua GAF </span>, <span style="color:blue">BLUE = desired GAF annotations</span>, <span style="color:magenta">MAGENTA = GAF annotations that would be made based on the current model if logical defs were in place for the inhibitor activity, but are questionable.</span>
 +
 +
{| class="wikitable" border="1"
 +
|-
 +
! Gene Name (col 2)
 +
! GO ID and term name (col 5)
 +
! Evidence (col 7)
 +
! Annotation Extension (col 16)
 +
! With/From (col 8)
 +
|-
 +
| <span style="color:green">CG7442 Dmel</span>
 +
| <span style="color:green">GO:0005277, acetylcholine transmembrane transporter activity</span>
 +
| <span style="color:green">IDA</span>
 +
| <span style="color:green">negatively_regulates(GO:0007271, synaptic transmission, cholinergic),negatively_regulates(GO:0007613, memory),RO:0002408(GO:0015464, acetylcholine receptor activity),positively_regulates(GO:0008355, olfactory learning)</span>
 +
|
 +
|-
 +
| <span style="color:green">CG7442 Dmel</span>
 +
| <span style="color:green">GO:0051630, acetylcholine uptake</span>
 +
| <span style="color:green">IDA</span>
 +
| <span style="color:green">occurs_in(GO:0098794), postsynapse</span>
 +
|
 +
|-
 +
||<span style="color:green">CG7442 Dmel</span>
 +
| <span style="color:green">GO:000030425, dendrite</span>
 +
| <span style="color:green">IDA</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:green">Ace Dmel</span>
 +
| <span style="color:green">GO:0003990, acetylcholineterase activity</span>
 +
| <span style="color:green">TAS</span>
 +
| <span style="color:green">negatively_regulates(GO:0007271, synaptic transmission, cholinergic),negatively_regulates(GO:0007613, memory),RO:0002408(GO:0015464, acetylcholine receptor activity)</span>
 +
|
 +
|-
 +
| <span style="color:green">Ace Dmel</span>
 +
| <span style="color:green">GO:0006581, acetylcholine catabolic process</span>
 +
| <span style="color:green">TAS</span>
 +
| <span style="color:green">occurs_in(GO:0043083, synaptic cleft)
 +
|
 +
|-
 +
| <span style="color:green">Ace Dmel</span>
 +
| <span style="color:green">GO:0043083, synaptic cleft</span>
 +
| <span style="color:green">TAS</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0005277, acetylcholine transmembrane transporter activity</span>
 +
| <span style="color:blue">IDA</span>
 +
| <span style="color:blue">occurs_in(GO:000030425, dendrite)</span>
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0051630, acetylcholine uptake</span>
 +
| <span style="color:blue">IDA</span>
 +
| <span style="color:blue">occurs_in(GO:0098794), postsynapse</span>
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:000030425, dendrite</span>
 +
| <span style="color:blue">IDA</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0051241, negative regulation of multicellular organismal process</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0090328, regulation of olfactory learning</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0032223, negative regulation of synaptic transmission, cholinergic</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0031645, negative regulation of neurological system process</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">CG7442 Dmel</span>
 +
| <span style="color:blue">GO:0048521, negative regulation of behavior</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0003990, acetylcholinesterase activity</span>
 +
| <span style="color:blue">TAS</span>
 +
| <span style="color:blue">occurs_in(GO:0043083, synaptic cleft)
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0006581, acetylcholine catabolic process</span>
 +
| <span style="color:blue">TAS</span>
 +
| <span style="color:blue">occurs_in(GO:0043083, synaptic cleft)
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0043083, synaptic cleft</span>
 +
| <span style="color:blue">TAS</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0032223, negative regulation of synaptic transmission, cholinergic</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0051241, negative regulation of multicellular organismal process</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0090328, regulation of olfactory learning</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0031645, negative regulation of neurological system process</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:blue">Ace Dmel</span>
 +
| <span style="color:blue">GO:0048521, negative regulation of behavior</span>
 +
| <span style="color:blue">IMP</span>
 +
|
 +
|
 +
|-
 +
| <span style="color:magenta">Ace Dmel</span>
 +
| <span style="color:magenta">GO:0030550, acetylcholine receptor inhibitor activity</span>
 +
| <span style="color:magenta">IC</span>
 +
| <span style="color:magenta">occurs_in(GO:0098794), postsynapse</span>
 +
| <span style="color:magenta">With/From: GO:0003990, acetylcholinesterase activity</span>
 +
|-
 +
| <span style="color:magenta">CG7442 Dmel</span>
 +
| <span style="color:magenta">GO:0030550, acetylcholine receptor inhibitor activity</span>
 +
| <span style="color:magenta">IC</span>
 +
| <span style="color:magenta">occurs_in(GO:0098794), postsynapse</span>
 +
| <span style="color:magenta">With/From: GO:0005277, acetylcholine transmembrane transporter activity</span>
 +
|-
 +
|}
  
 
=Minutes=
 
=Minutes=
 +
*On call: Antonia, Bob, Chris, David H., David O-S., Giulia, Helen, Judy, Kimberly, Li, Melanie, Midori, Peter, Petra, Ruth, Sabrina, Shur-Jen, Val 
 +
 +
==Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016==
 +
*Please fill in the attendees table on the [http://wiki.geneontology.org/index.php/2016_Los_Angeles_GOC_Meeting_Logistics logistics page] and also indicate whether you can attend a Noctua/LEGO workshop on either end of the official GOC meeting
 +
 +
==Annotation Consistency Exercise for the Remainder of 2016==
 +
*We will continue with the current format for the remainder of 2016
 +
*Please send thoughts and suggestions to David and Kimberly, if you have them
 +
*Next year's calls will likely incorporate more discussion of LEGO models
 +
 +
==Questions about Membrane Cellular Component Annotations==
 +
*Please see Rebecca's proposal on the 2016-07-12 minutes
 +
*Issue of using more descriptive, combinatorial evidence codes discussed in this proposal applies to curation beyond membrane CC annotations, so we will pick up this discussion in August and try to find the best overall solution
 +
 +
==LEGO Model for FlyBase Annotation Consistency Exercise Paper==
 +
*David presented the LEGO model that he, Giulia, Helen, and Kimberly worked on for the Drosophila memory paper
 +
*Key questions/issues that came up about the LEGO model:
 +
**Function-Process links - would these be automatically generated?
 +
***In this model, one of the MF annotations is to acetylcholinesterase activity
 +
***''If'' there was an MF-BP link in the ontology to the BP acetylcholine catabolic process, would this automatically be generated?
 +
***This doesn't happen currently, but could only happen if that was the extent of the information (i.e. there was no additional contextual information, such as CC, included in the MF annotation)
 +
**Use of directly_inhibits relation to describe the effects of the transporter and acetylcholinesterase on the acetylcholine receptor activity
 +
***The current definition of directly_inhibits is ??  Can't find this in the OLS or the RO. 
 +
***From a PowerPoint slide Kimberly had from Paul T., the working definition included cases where the upstream activity directly_inhibits the downstream activity when the upstream activity removes a small molecule required for the function of the downstream activity.
 +
***This definition fits with the proposed mechanism of the transporter and acetylcholinesterase, but many curators found its use unsatisfactory because it is different from how the directly_inhibits relation is used wrt, e.g. enzyme regulators, where there is direct physical association to regulate the activity of the enzyme
 +
***What other options are there to describe this relationship?  What flavor of regulation is 'removing a substrate'?
 +
***David O-S. suggested a new BP term for 'regulation of neurotransmitter levels in synaptic cleft' and then having the two upstream activities point to that term - with what relation?  This would make the mechanism of action of the upstream activities clearer.
 +
**What does regulation of memory mean?
 +
***This issue led to discussion of this paper in the first place.
 +
***The model has negatively regulates relations between the activities and memory, but the underlying mechanism is not clear, so the resulting post-composed term, negative regulation of memory, is a bit vague.
 +
***This is an area of the ontology where we'd like some expert opinion to help flesh out the molecular mechanisms of memory formation, retention, recall, and the relationship between learning and memory.
 +
**Instance level representation in LEGO models
 +
***Curators need to keep in mind, when they are creating models, that these are instance-level representations
 +
***This makes inclusion of contextual information very important, as mechanisms for BPs could be different depending on cell type
 +
**Redundancy in annotation?
 +
***There are two separate negatively regulates relations from the transporter activity to regulation of synaptic transmission and memory.  Would one have been enough, if the curator was inferring that regulation of synaptic transmission was the mechanism for regulating memory? 
 +
***Because there was different evidence for each of the separate assertions, there were separate relations between the transporter and the two BPs
 +
**Capturing CC for MF vs BP
 +
***The CC contextual information for linked MFs and BPs may not always be the same
 +
***This is because the activities that are part of a BP may not all occur in the same subcellular location - signaling pathways are good examples of this
 +
*We then compared the GAF currently generated by Noctua to the annotations that a curator would make using conventional GO annotation practices
 +
**Key issues/questions that came up:
 +
***In the annotation extensions, Noctua comma-separated the four BPs for the transporter activity.  Should these have been pipe-separated?
 +
****This goes back to the discussion about instance-level representation in LEGO models.  If the curator feels that the same MF instance is involved in each of these processes, then the comma-separated representation is okay.  If one or more of the BPs is believed to be the result of separate instances of the MF, then the curator would need to create another instance of the MF so that the annotation extensions were parsed out to separate MFs to accurately reflect the biology.
 +
***CC contextual information
 +
****Right now, the CC contextual information is being captured solely as a C annotation line in the GAF
 +
****Ideally, it should be captured as both a C annotation as well as contextual information using the occurs_in relation and annotation extensions
 +
***Capturing separate regulation annotations from regulates relations in LEGO models
 +
****This model has a number of regulates relations between activities and processes
 +
****Currently, this information is being captured as annotation extensions in the resulting GAF, but curators would like to also have these relations be captured as separate BP annotations
 +
****To do this requires logical definitions of existing regulates terms and creation of new regulation terms if the model proposes those relations and the terms don't yet exist.  In the interim, the reasoner looks for the most granular matching regulation parent term in the ontology, although these can sometimes be high level terms that don't sufficiently capture the biology.
 +
****Jim B. starts next week and he will work on getting the GAF/GPAD output of LEGO models to include more of these annotations that the curators (and users) would want
 +
****See the [https://github.com/geneontology/noctua/issues/321 corresponding github ticket 321]
 +
  
  
 
[[Category: Annotation Working Group]]
 
[[Category: Annotation Working Group]]

Latest revision as of 11:14, 27 July 2016

Bluejeans URL: https://bluejeans.com/993661940

Agenda

Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016

  • Please indicate on the Meeting Logistics Page if you plan to come.
  • We are also gauging interest in a one- or half-day Noctua/LEGO workshop at USC (either before or after the main consortium meeting) so have added two additional column to the table to see if people can also attend that, and if so, when.
  • Please add your information as soon as possible so we can make arrangements.

Annotation Consistency Exercise for the Remainder of 2016

  • Thanks to everyone who agreed to select and present a paper for the remainder of this year:
  • August 23 - SGD
  • September 27 - dictyBase
  • October 25 - RGD
  • November 22 - Zfin
  • If you have thoughts about the exercises, please send them along to David and Kimberly. At the end of the year, we will again evaluate how this is working and if we need to make any changes to the format to keep these exercises useful for people.

Revised Protein Binding Documentation

  • GO website has been updated with the following guideline on protein binding annotations:
 Proposed New Guideline: The Molecular Function (MF) ontology can be used to capture macromolecular interactions, such as protein-
 protein, protein-nucleic acid, protein-lipid interactions, etc.  While GO annotations are not considered to be a repository of all 
 protein-protein interactions, many gene products are annotated to 'protein binding' (GO:0005515) or one of its child terms.  In making 
 these annotations, contributing groups may follow slightly different practices with respect to the types of experimental evidence used 
 to support these inferences, e.g. some groups may use co-immunoprecipitation as supporting evidence for a protein binding annotation 
 between two gene products, others not.  However, all groups generally adhere to the principle that, when annotated, protein binding 
 interactions inform what is believed to be the normal biological role of a gene product, i.e. the protein-protein interactions support 
 an author's hypothesis about how the gene product is thought to execute its molecular function in the context of a normal biological 
 process.  Protein-protein interactions for which there is not yet sufficient biological context are discouraged as sources of GO MF 
 annotations.
  • Also, the GO FAQs have been updated to document how protein-protein interactions curated by IntAct are exported to GO as protein binding (GO:0005515) annotations.

Questions about Membrane Cellular Component Annotations

  • This annotation issue was raised by Rebecca and concerns annotation to membrane child terms, e.g. integral to synaptic vesicle membrane, given different types of experimental results.
  • We will resume discussion of this issue when Rebecca is back.
  • In the meantime, there is a nice summary from Rebecca on the 2016-07-11 minutes.
  • Please take a look and review the discussion and proposal so we can move towards creating guidelines on the 2016-08-09 call.

LEGO Model for FlyBase Annotation Consistency Exercise Paper

  • Review annotations to paper on memory and relations between them in LEGO model
  • Review resulting GAF (from Model drop-down menu, select Export GAF)
  • Review additional annotations desired from a GAF output.
  • Review use of directly_inhibits relation between acetylcholine transporter and receptor activities in LEGO model and annotation to inhibitor activity based on the definition.
  • Compare with annotations submitted from consistency exercise
  • GREEN = Noctua GAF , BLUE = desired GAF annotations, MAGENTA = GAF annotations that would be made based on the current model if logical defs were in place for the inhibitor activity, but are questionable.
Gene Name (col 2) GO ID and term name (col 5) Evidence (col 7) Annotation Extension (col 16) With/From (col 8)
CG7442 Dmel GO:0005277, acetylcholine transmembrane transporter activity IDA negatively_regulates(GO:0007271, synaptic transmission, cholinergic),negatively_regulates(GO:0007613, memory),RO:0002408(GO:0015464, acetylcholine receptor activity),positively_regulates(GO:0008355, olfactory learning)
CG7442 Dmel GO:0051630, acetylcholine uptake IDA occurs_in(GO:0098794), postsynapse
CG7442 Dmel GO:000030425, dendrite IDA
Ace Dmel GO:0003990, acetylcholineterase activity TAS negatively_regulates(GO:0007271, synaptic transmission, cholinergic),negatively_regulates(GO:0007613, memory),RO:0002408(GO:0015464, acetylcholine receptor activity)
Ace Dmel GO:0006581, acetylcholine catabolic process TAS occurs_in(GO:0043083, synaptic cleft)
Ace Dmel GO:0043083, synaptic cleft TAS
CG7442 Dmel GO:0005277, acetylcholine transmembrane transporter activity IDA occurs_in(GO:000030425, dendrite)
CG7442 Dmel GO:0051630, acetylcholine uptake IDA occurs_in(GO:0098794), postsynapse
CG7442 Dmel GO:000030425, dendrite IDA
CG7442 Dmel GO:0051241, negative regulation of multicellular organismal process IMP
CG7442 Dmel GO:0090328, regulation of olfactory learning IMP
CG7442 Dmel GO:0032223, negative regulation of synaptic transmission, cholinergic IMP
CG7442 Dmel GO:0031645, negative regulation of neurological system process IMP
CG7442 Dmel GO:0048521, negative regulation of behavior IMP
Ace Dmel GO:0003990, acetylcholinesterase activity TAS occurs_in(GO:0043083, synaptic cleft)
Ace Dmel GO:0006581, acetylcholine catabolic process TAS occurs_in(GO:0043083, synaptic cleft)
Ace Dmel GO:0043083, synaptic cleft TAS
Ace Dmel GO:0032223, negative regulation of synaptic transmission, cholinergic IMP
Ace Dmel GO:0051241, negative regulation of multicellular organismal process IMP
Ace Dmel GO:0090328, regulation of olfactory learning IMP
Ace Dmel GO:0031645, negative regulation of neurological system process IMP
Ace Dmel GO:0048521, negative regulation of behavior IMP
Ace Dmel GO:0030550, acetylcholine receptor inhibitor activity IC occurs_in(GO:0098794), postsynapse With/From: GO:0003990, acetylcholinesterase activity
CG7442 Dmel GO:0030550, acetylcholine receptor inhibitor activity IC occurs_in(GO:0098794), postsynapse With/From: GO:0005277, acetylcholine transmembrane transporter activity

Minutes

  • On call: Antonia, Bob, Chris, David H., David O-S., Giulia, Helen, Judy, Kimberly, Li, Melanie, Midori, Peter, Petra, Ruth, Sabrina, Shur-Jen, Val

Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016

  • Please fill in the attendees table on the logistics page and also indicate whether you can attend a Noctua/LEGO workshop on either end of the official GOC meeting

Annotation Consistency Exercise for the Remainder of 2016

  • We will continue with the current format for the remainder of 2016
  • Please send thoughts and suggestions to David and Kimberly, if you have them
  • Next year's calls will likely incorporate more discussion of LEGO models

Questions about Membrane Cellular Component Annotations

  • Please see Rebecca's proposal on the 2016-07-12 minutes
  • Issue of using more descriptive, combinatorial evidence codes discussed in this proposal applies to curation beyond membrane CC annotations, so we will pick up this discussion in August and try to find the best overall solution

LEGO Model for FlyBase Annotation Consistency Exercise Paper

  • David presented the LEGO model that he, Giulia, Helen, and Kimberly worked on for the Drosophila memory paper
  • Key questions/issues that came up about the LEGO model:
    • Function-Process links - would these be automatically generated?
      • In this model, one of the MF annotations is to acetylcholinesterase activity
      • If there was an MF-BP link in the ontology to the BP acetylcholine catabolic process, would this automatically be generated?
      • This doesn't happen currently, but could only happen if that was the extent of the information (i.e. there was no additional contextual information, such as CC, included in the MF annotation)
    • Use of directly_inhibits relation to describe the effects of the transporter and acetylcholinesterase on the acetylcholine receptor activity
      • The current definition of directly_inhibits is ?? Can't find this in the OLS or the RO.
      • From a PowerPoint slide Kimberly had from Paul T., the working definition included cases where the upstream activity directly_inhibits the downstream activity when the upstream activity removes a small molecule required for the function of the downstream activity.
      • This definition fits with the proposed mechanism of the transporter and acetylcholinesterase, but many curators found its use unsatisfactory because it is different from how the directly_inhibits relation is used wrt, e.g. enzyme regulators, where there is direct physical association to regulate the activity of the enzyme
      • What other options are there to describe this relationship? What flavor of regulation is 'removing a substrate'?
      • David O-S. suggested a new BP term for 'regulation of neurotransmitter levels in synaptic cleft' and then having the two upstream activities point to that term - with what relation? This would make the mechanism of action of the upstream activities clearer.
    • What does regulation of memory mean?
      • This issue led to discussion of this paper in the first place.
      • The model has negatively regulates relations between the activities and memory, but the underlying mechanism is not clear, so the resulting post-composed term, negative regulation of memory, is a bit vague.
      • This is an area of the ontology where we'd like some expert opinion to help flesh out the molecular mechanisms of memory formation, retention, recall, and the relationship between learning and memory.
    • Instance level representation in LEGO models
      • Curators need to keep in mind, when they are creating models, that these are instance-level representations
      • This makes inclusion of contextual information very important, as mechanisms for BPs could be different depending on cell type
    • Redundancy in annotation?
      • There are two separate negatively regulates relations from the transporter activity to regulation of synaptic transmission and memory. Would one have been enough, if the curator was inferring that regulation of synaptic transmission was the mechanism for regulating memory?
      • Because there was different evidence for each of the separate assertions, there were separate relations between the transporter and the two BPs
    • Capturing CC for MF vs BP
      • The CC contextual information for linked MFs and BPs may not always be the same
      • This is because the activities that are part of a BP may not all occur in the same subcellular location - signaling pathways are good examples of this
  • We then compared the GAF currently generated by Noctua to the annotations that a curator would make using conventional GO annotation practices
    • Key issues/questions that came up:
      • In the annotation extensions, Noctua comma-separated the four BPs for the transporter activity. Should these have been pipe-separated?
        • This goes back to the discussion about instance-level representation in LEGO models. If the curator feels that the same MF instance is involved in each of these processes, then the comma-separated representation is okay. If one or more of the BPs is believed to be the result of separate instances of the MF, then the curator would need to create another instance of the MF so that the annotation extensions were parsed out to separate MFs to accurately reflect the biology.
      • CC contextual information
        • Right now, the CC contextual information is being captured solely as a C annotation line in the GAF
        • Ideally, it should be captured as both a C annotation as well as contextual information using the occurs_in relation and annotation extensions
      • Capturing separate regulation annotations from regulates relations in LEGO models
        • This model has a number of regulates relations between activities and processes
        • Currently, this information is being captured as annotation extensions in the resulting GAF, but curators would like to also have these relations be captured as separate BP annotations
        • To do this requires logical definitions of existing regulates terms and creation of new regulation terms if the model proposes those relations and the terms don't yet exist. In the interim, the reasoner looks for the most granular matching regulation parent term in the ontology, although these can sometimes be high level terms that don't sufficiently capture the biology.
        • Jim B. starts next week and he will work on getting the GAF/GPAD output of LEGO models to include more of these annotations that the curators (and users) would want
        • See the corresponding github ticket 321