Annotation Conf. Call 2017-02-28: Difference between revisions
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= Minutes = | = Minutes = | ||
*On call: David H | *On call: Alice, Barbara, Chris G, David H, David OS, Edith, George, Giulia, GOA, Harold, Helen, Karen, Kimberly, Li, Midori, Pascale, Paul, Ruth, Sabrina, Stacia, Stan, Tanya, Terry, Petra | ||
== Noctua Modeling == | |||
=== Sabrina (Zfin) - role of TFs in neutrophil maturation === | |||
**Two TFs, C-myb and Cebp1 | |||
**Represent TFs with MF term for transcription factor activity, sequence-specific DNA binding | |||
**Indicate gene promoter bound with has_input (lyz) | |||
**occurs_in: | |||
***chromatin - based on ChIp assay | |||
**part_of: | |||
***transcription - based on direct assays and mutant phenotypes | |||
**transcription factor complex | |||
***based on co-IP of C-myb and Cebp1 | |||
**There is no information about the precise role of lyz in neutrophil maturation | |||
**Transcription part_of cell maturation | |||
***Based on mutant phenotype | |||
**Neutrophil maturation didn't exist in GO | |||
***Created term by linking cell maturation 'results in maturation of' neutrophil | |||
***Evidence was direct assay based on what the authors show about this process | |||
**Questions: | |||
***Harold - transcription factor complex - why is there a separate individual for the complex as well as both each TFs separately? | |||
****Sabrina - this is what the data suggested | |||
***Karen - can use the more specific RNA polII transcription factor activity? | |||
****Sabrina - Yes, could do this. | |||
***Kimberly - Might be a nice check to have to prompt curators to use the more specific MF term when the more specific BP term is also used. | |||
***David H - What would the reasoner give if we run it? | |||
***Paul T. - The coming design templates should include transcription and will give curators a standard way to annotate these things. Curators will then just need to fill in the specific entities and evidence. | |||
***Tried running the reasoner | |||
***David OS - discussion about use of 'directly activates' | |||
****In this case, 'directly activates' feels right, but we need guidelines | |||
***Karen - there are guidelines for this as part of the TF annotation guidelines | |||
***Paul T. - 'direct' means a direct physical interaction between two entities that execute the functions | |||
***David OS - need guidance about when to use 'directly positively regulates' between an MF and a BP | |||
***Karen - does this suggest that the current transcription curation guidelines are too narrow? | |||
***Paul T. - this representation of transcription was arrived at after looking at several different possibilities and was thought to be the most intuitive representation. We need to make sure we have a standard representation, though. Even if this is ultimately not the way we want to go, we need to have a standard view. | |||
***David OS - we also need to make sure we align the representation of transcription in Noctua models is the same as in the ontology | |||
'''AI: Make a ticket wrt consistent representation of transcription in the ontology and Noctua.''' - David making now. | |||
=== Midori - Regulation of Myosin Activity === | |||
*Examining the role of the myosin regulatory light chain - what activities can be associated with it? | |||
*Role of myosin in actomyosin contractile ring contraction is well studied, accepted | |||
*Paper looks at rlc1 mutants and the subsequent effects on myo2 activity | |||
*Some unknown regulatory activity of rlc1 regulates the motor activity of which myo2 is a part | |||
*But we thought about representing this as rlc1 directly regulates myo2 | |||
**Why? - It is known that rlc1 binds myo2 and rlc1 can affect myo2 activity in in vitro assays when the only participants are the myosin complex and actin filaments | |||
*The ontology classifies motor activity as a type of nucleoside triphosphatase activity | |||
**If we said that rlc1 directly regulates myo2, then we would expect the reasoner to also say that rlc1 regulates the nucleoside triphosphate activity | |||
**However, this would be wrong, because the paper shows that rlc1 doesn't change the myo2 ATPase activity | |||
*Questions: | |||
**Is the representation of motor activity in the ontology correct? | |||
***No, it is a complex molecular function that needs to be represented as such in the ontology. | |||
**Can we use a NOT annotation to indicate that the data doesn't support regulation of the ATPase activity? | |||
**Karen - can you use PRO representation of modified forms to indicate that role of the specifically phosphorylated rlc1? | |||
**Does Noctua allow NOT annotations? | |||
***No, but there is a ticket for this. | |||
**Paul T - how deep into the mechanism do we want to go? | |||
***Could say that the regulation is direct, use whatever evidence is available to support that. | |||
***Then, if we know what subfunction is actually regulated, we could capture that in GO. | |||
**Midori - concern with saying that the regulation is direct is that, at present, we'd wind up with an incorrect inference due to the current placement of motor activity in the ontology | |||
**Paul T - would make the annotation, don't put the model into production, and then put in a ticket to correct the ontology | |||
**Midori - PomBase would probably wait on this right now | |||
**Paul T - biological processes are programs made up of molecular activities | |||
**David OS - can fix the ontology for this | |||
***We need a generic fix for functions where ATP is used as an energy source | |||
***How would we describe the effector activity of the motor? | |||
**David H - this issue of incorrect inferences from compound molecular functions has been around for a while, and the MF refactor should help address it | |||
'''AI: Add this example to the github repository for MF refactor.''' | |||
**Tanya - Bigger picture: do we want to capture everything we know about a set of gene products in a model? The direct binding of rlc1 and myo2? Where does that go, if anywhere? Or do we want to keep models ‘clean’ and showing only one process? | |||
**Stacia - what is sustainable for Noctua curation? If you can import everything from a Noctua model, that might make sense, otherwise it becomes difficult to view and understand. | |||
**Tanya - Where would the known binding between myo2 and rlc1 be included in this model? | |||
**Kimberly - Use binding information as supportive evidence for the direct regulatory relationship? | |||
**Midori - Could represent the activity as being enabled by the complex and articulate the activities of each member of the complex? | |||
=== Next Meetings === | |||
*March 14th - regular annotation group call | |||
*April 11th - regular annotation group call | |||
*We will not have a call on March 28th, as it overlaps with ISB meeting at Stanford. | |||
[[Category: Annotation Working Group]] | [[Category: Annotation Working Group]] |
Latest revision as of 13:05, 28 February 2017
Bluejeans URL
https://bluejeans.com/993661940
Agenda
GO Meeting Reminder
- Corvallis, Oregon - June 1-3rd, Noctua Workshop - June 4th, Reactome Workshop - June 5th
- Meeting Registration Site
- Meeting Agenda
Noctua Modeling Discussion
Sabrina Toro, Zfin
- ZDB-PUB-160610-16 myb, cebp1 and neutrophil maturation
- c-Myb acts in parallel and cooperatively with Cebp1 to regulate neutrophil maturation in zebrafish.
Midori Harris, PomBase
- myo2_rlc1_PMID19570908
- Regulation of fission yeast myosin-II function and contractile ring dynamics by regulatory light-chain and heavy-chain phosphorylation.
- In vitro and in vivo assays using nonphosphorylatable or phosphomimetic Rlc1 mutations show that Rlc1 somehow positively regulates the actin filament-based motor activity of Myo2 as part of actomyosin contractile ring contraction, in turn part of mitotic cytokinesis.
- We were very tempted to say that Rlc1's unknown MF regulator activity directly positively regulates Myo2's microfilament motor activity because:
- Rlc1 has previously been shown to bind Myo2;
- The in vitro assays (Fig.1, Table 3) show an effect on Myo2 motor activity with only F-actin, Myo2, Cdc4. and Rlc1 (heavy chain, essential light chain, and regulatory light chains respectively) present.
- The reason we didn't, and instead included the actin filament-based movement "link", is that the is_a hierarchy has motor activity as a subtype of NTPase activity:
- We were very tempted to say that Rlc1's unknown MF regulator activity directly positively regulates Myo2's microfilament motor activity because:
GO:0017111 ! nucleoside-triphosphatase activity -- is_a GO:0003774 ! motor activity ---- is_a GO:0000146 ! microfilament motor activity
- From this, reasoning would infer this regulation hierarchy (whether regulation terms are instantiated or not):
regulation of nucleoside-triphosphatase activity -- is_a regulation of motor activity ---- is_a regulation of microfilament motor activity
- ... and erroneously conclude that Rlc1 does regulate Myo2's ATPase activity. The Rlc1 mutant phenotypes here say it doesn't (Fig. 76, Table 3).
- Questions:
- Should the MF ontology change to motor activity has_part nucleoside-triphosphatase activity?
- Does LEGO have any way to capture when a molecular mechanism isn't known, but one possibility has been ruled out?
April Discussion
- April 25th
- Sign up: LEGO Discussion Rota
Minutes
- On call: Alice, Barbara, Chris G, David H, David OS, Edith, George, Giulia, GOA, Harold, Helen, Karen, Kimberly, Li, Midori, Pascale, Paul, Ruth, Sabrina, Stacia, Stan, Tanya, Terry, Petra
Noctua Modeling
Sabrina (Zfin) - role of TFs in neutrophil maturation
- Two TFs, C-myb and Cebp1
- Represent TFs with MF term for transcription factor activity, sequence-specific DNA binding
- Indicate gene promoter bound with has_input (lyz)
- occurs_in:
- chromatin - based on ChIp assay
- part_of:
- transcription - based on direct assays and mutant phenotypes
- transcription factor complex
- based on co-IP of C-myb and Cebp1
- There is no information about the precise role of lyz in neutrophil maturation
- Transcription part_of cell maturation
- Based on mutant phenotype
- Neutrophil maturation didn't exist in GO
- Created term by linking cell maturation 'results in maturation of' neutrophil
- Evidence was direct assay based on what the authors show about this process
- Questions:
- Harold - transcription factor complex - why is there a separate individual for the complex as well as both each TFs separately?
- Sabrina - this is what the data suggested
- Karen - can use the more specific RNA polII transcription factor activity?
- Sabrina - Yes, could do this.
- Kimberly - Might be a nice check to have to prompt curators to use the more specific MF term when the more specific BP term is also used.
- David H - What would the reasoner give if we run it?
- Paul T. - The coming design templates should include transcription and will give curators a standard way to annotate these things. Curators will then just need to fill in the specific entities and evidence.
- Tried running the reasoner
- David OS - discussion about use of 'directly activates'
- In this case, 'directly activates' feels right, but we need guidelines
- Karen - there are guidelines for this as part of the TF annotation guidelines
- Paul T. - 'direct' means a direct physical interaction between two entities that execute the functions
- David OS - need guidance about when to use 'directly positively regulates' between an MF and a BP
- Karen - does this suggest that the current transcription curation guidelines are too narrow?
- Paul T. - this representation of transcription was arrived at after looking at several different possibilities and was thought to be the most intuitive representation. We need to make sure we have a standard representation, though. Even if this is ultimately not the way we want to go, we need to have a standard view.
- David OS - we also need to make sure we align the representation of transcription in Noctua models is the same as in the ontology
- Harold - transcription factor complex - why is there a separate individual for the complex as well as both each TFs separately?
AI: Make a ticket wrt consistent representation of transcription in the ontology and Noctua. - David making now.
Midori - Regulation of Myosin Activity
- Examining the role of the myosin regulatory light chain - what activities can be associated with it?
- Role of myosin in actomyosin contractile ring contraction is well studied, accepted
- Paper looks at rlc1 mutants and the subsequent effects on myo2 activity
- Some unknown regulatory activity of rlc1 regulates the motor activity of which myo2 is a part
- But we thought about representing this as rlc1 directly regulates myo2
- Why? - It is known that rlc1 binds myo2 and rlc1 can affect myo2 activity in in vitro assays when the only participants are the myosin complex and actin filaments
- The ontology classifies motor activity as a type of nucleoside triphosphatase activity
- If we said that rlc1 directly regulates myo2, then we would expect the reasoner to also say that rlc1 regulates the nucleoside triphosphate activity
- However, this would be wrong, because the paper shows that rlc1 doesn't change the myo2 ATPase activity
- Questions:
- Is the representation of motor activity in the ontology correct?
- No, it is a complex molecular function that needs to be represented as such in the ontology.
- Can we use a NOT annotation to indicate that the data doesn't support regulation of the ATPase activity?
- Karen - can you use PRO representation of modified forms to indicate that role of the specifically phosphorylated rlc1?
- Does Noctua allow NOT annotations?
- No, but there is a ticket for this.
- Paul T - how deep into the mechanism do we want to go?
- Could say that the regulation is direct, use whatever evidence is available to support that.
- Then, if we know what subfunction is actually regulated, we could capture that in GO.
- Midori - concern with saying that the regulation is direct is that, at present, we'd wind up with an incorrect inference due to the current placement of motor activity in the ontology
- Paul T - would make the annotation, don't put the model into production, and then put in a ticket to correct the ontology
- Midori - PomBase would probably wait on this right now
- Paul T - biological processes are programs made up of molecular activities
- David OS - can fix the ontology for this
- We need a generic fix for functions where ATP is used as an energy source
- How would we describe the effector activity of the motor?
- David H - this issue of incorrect inferences from compound molecular functions has been around for a while, and the MF refactor should help address it
- Is the representation of motor activity in the ontology correct?
AI: Add this example to the github repository for MF refactor.
- Tanya - Bigger picture: do we want to capture everything we know about a set of gene products in a model? The direct binding of rlc1 and myo2? Where does that go, if anywhere? Or do we want to keep models ‘clean’ and showing only one process?
- Stacia - what is sustainable for Noctua curation? If you can import everything from a Noctua model, that might make sense, otherwise it becomes difficult to view and understand.
- Tanya - Where would the known binding between myo2 and rlc1 be included in this model?
- Kimberly - Use binding information as supportive evidence for the direct regulatory relationship?
- Midori - Could represent the activity as being enabled by the complex and articulate the activities of each member of the complex?
Next Meetings
- March 14th - regular annotation group call
- April 11th - regular annotation group call
- We will not have a call on March 28th, as it overlaps with ISB meeting at Stanford.