Annotation Conf. Call, June 23, 2015

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Agenda

Ability to add comments to an annotation

We want to be able to capture why a particular experiment/result was not captured as an annotation and make this comment visible to the public. This issue came up during the April curation consistency discussion (mouse paper). I made a github ticket. https://github.com/ebi-uniprot/Protein2GO/issues/1 How should we control this field so we don't write long sentences? Limit it to 140 characters? Other ideas?

obsolete relationships

There are some relationships that were obsoleted (mostly for use with col-16). Not sure how other groups are rehousing these annotations. Instead of a regular consistency exercise is it okay if we go through some of the papers and get your input on how to rehouse those col-16 data?

Note there are also 2 relationships which have been suggested to be obsoleted: dependent on in presence of

These pages list some of the use cases and try to suggest alternative ways to capture this data. A similar approach is required for the relationships that are now obsolete.

June Consistency paper

http://www.ncbi.nlm.nih.gov/pubmed/?term=23954377

Comments from groups re annotation

  • Ouabain plant derived drug used to treat hypotension and some arrhythmias, but also toxic.
  • We debated about annotating to sodium:potassium-exchanging ATPase activity - GO:0005391, but there is no exp. evidence to show that there was indeed exchange of these ions. There is no data for the term ATPase, coupled either. Without using background knowledge we cannot make the granular annotation based on just this paper.
  • The authors express ATP1A2 and ATP1B1. But there is not enough data in this paper to say that alpha and beta subunits contribute to the activity. So we did not capture annotations to beta subunit.
  • Normally we won't make the annotations to potassium ion binding and sodium ion binding, but if this is the only paper on this protein these annotations are acceptable
  • There is no background measurement for activity without the transfected proteins (negative control) - although there are measurements for activity of mutants which have lower activity.
  • Should there be a connection in the ontology tree between the terms ATP binding and ATPase activity.
  • Annotation to sodium:potassium-exchanging ATPase activity is necessary for annotation to complex GO:0005890 sodium:potassium-exchanging ATPase complex

Discusion

Adding comments to annotations

This feature was a suggestion from a previous call and Rama made a ticket in github to make sure it is not lost. protein2GO can easily accommodate this new feature. But before we implement it, how do we make sure it is used in a controlled way, correctly/sparingly? How do we display it in AmiGO? Please think about these points (and any other issues) and bring them to the next annotation call. Please bring use cases to justify your stand!

Obsoleting relationships

  • relationships that are used for col-16 needs to be managed better. gorel.obo is not in sync with what protein2GO does.
  • We need to provide examples for the relationships that are in use. Ruth and Rachael have been working on this and David OS has put the pages in github.
  • Petra mentioned that she got an email from protein2GO about the obsolete relationships and she ended up deleting many of the col-16 data because there was no other way to capture those details. It is lot of work to go back to the paper and reannoate. So it would be useful to have a replaced relationship.
  • everybody was okay with bringing specific examples of col-16 to the next consistency exercise.

Curation Consistency

  • David hill: this paper was simple yet tricky. Is this a standard assay and is this something curators should trust and curate? Does the assay reflect the activity of the enzyme?
  • Many of us agreed that they did not show the Na-K exchange part and they showed just ATPase activity in the presence of K and Na. There is lot of background information to consider though.
  • PaulT: is there evidence in another paper for this activity? What is the story they are testing in this paper? They are trying to make mutants in ATP1A1 because there were several cases of migrane associated with these mutations. We should not make piecemeal annotations. Try to tell the complete story.
  • Rama: different groups annotate differently. the goal of this exercise is to go through the data, and tease out what is annotatable, what should the terms be/ev.code be etc. Some groups may not use this paper to annotate at all and might go to a different one where the activity was published.
    • Ruth: this gene has more than 300 papers. Annotating human genes which have lot of papers is tricky. No time. So we want to do the best as we go through a paper.
    • PaulT: That is a valid reason.
  • There was general agreement that we want to make the most informative annotation from the paper. So annotating to Na-K exchange ATPase would be okay from this paper (both subunits with contributes to)
  • Rama: Does it make sense to annotate to drug binding (other binding annotations)? The authors did these binding assays to see if the protein conformation changed.
    • Ruth: people working on human genes would like to know how many genes bind to this drug.
    • Rama: GO is to capture function not some property of the gene product. May be we are overloading GO?
  • PaulT: When we are annotating function, the question we want to ask is: what is the function of this gene in this organism? What did the gene evolve to do in this organism?
    • revisit why drug binding (and other small molecule binding terms) are in the ontology. Agenda item for the GOC
  • Annotation to Membrane is okay.
  • Annotation to Na-K complex? Authors talk about it indirectly. Not wrong to make this annotation.
  • ATP metabolic process: NO. ATP hydrolysis is to get energy. This is not the main process this gp is involved in.


Annotation Summary

Gene Qualifier Term ID # of Annotations Evidence Code Summary 'With' field Summary Extension Summary Comments
Molecular Function Annotations
ATP1A2 contributes_to drug binding GO:0008144 1/4 IPI CHEBI:472805 - ouabain take to GO meeting, this is not a normal function, do other databases capture this? Add for now although maybe deleted in future
ATP1B1 contributes_to drug binding GO:0008144 1/4 IPI CHEBI:472805 - ouabain ditto
ATP1A2 contributes_to carbohydrate derivative binding GO:0097367 1/4 IPI CHEBI:472805 - ouabain this is not the function of the protein, this is an experimentally forced 'activity'
ATP1B1 contributes_to carbohydrate derivative binding GO:0097367 1/4 IPI CHEBI:472805 - ouabain ditto
ATP1A2 contributes_to sodium ion binding GO:0031402 2/4 IDA-1, IMP-1
ATP1A2 sodium ion binding GO:0031402 1/4 IDA, IMP (in_presence_of CHEBI:29103 Potassium AND P05026 ATP1B1) this additional AE information makes the annotation more complex than it needs to be and means that ATP1B1 is not annotated
ATP1B1 contributes_to sodium ion binding GO:0031402 2/4 IDA
ATP1A2 contributes_to potassium ion binding GO:0030955 2/4 IDA-1, IMP-1
ATP1A2 potassium ion binding GO:0030955 1/4 IDA, IMP (in_presence_of CHEBI:29101 Sodium AND P05026 ATP1B1) this additional AE information makes the annotation more complex than it needs to be and means that ATP1B1 is not annotated
ATP1B1 contributes_to potassium ion binding GO:0030955 2/4 IDA
ATP1A2 contributes_to ATPase activity GO:0016887 2/4 IDA-1, IMP-1 1/4: (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding) this additional AE information makes the annotation more complex than it needs to be
ATP1A2 ATPase activity GO:0016887 1/4 IDA, IMP (in_presence_of CHEBI:29101 Sodium AND CHEBI:29103 Potassium AND UniProt: P05026 ATP1B1) this additional AE information makes the annotation more complex than it needs to be and means that ATP1B1 is not annotated
ATP1B1 contributes_to ATPase activity GO:0016887 2/4 IDA 1/4: (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding) ditto
ATP1A2 contributes_to ATP binding GO:0005524 2/4 IDA-1, IMP-1 1/4: (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding) this additional AE information makes the annotation more complex than it needs to be
ATP1B1 contributes_to ATP binding GO:0005524 2/4 IDA 1/4: (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding) ditto
ATP1A2 ATPase binding GO:0051117 1/4 IPI ATP1B1
ATP1B1 ATPase binding GO:0051117 1/4 IPI ATP1A2
ATP1A2 contributes_to sodium:potassium-exchanging ATPase activity GO:0005391 1/4 IDA/IMP It was agreed that the assays undertaken were standard assays used to demonstrate that this protein complex has sodium:potassium-exchanging ATPase activity and that GO should be capturing the authors intent and the biological role of a protein
ATP1A2 contributes_to sodium:potassium-exchanging ATPase activity GO:0005391 1/4 IC GO:0031402 sodium ion binding, GO:0030955 potassium ion binding, GO:0016887 ATPase activity, GO:0016020 membrane
ATP1B1 contributes_to sodium:potassium-exchanging ATPase activity GO:0005391 1/4 IDA/IMP It was agreed that the assays undertaken were standard assays used to demonstrate that this protein complex has sodium:potassium-exchanging ATPase activity and that GO should be capturing the authors intent and the biological role of a protein
ATP1B1 contributes_to sodium:potassium-exchanging ATPase activity GO:0005391 1/4 IC GO:0031402 sodium ion binding, GO:0030955 potassium ion binding, GO:0016887 ATPase activity, GO:0016020 membrane
Biological Process Annotations
ATP1A2 ATP metabolic process GO:0046034 1/4 IMP (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding, GO:0016887 ATPase activity) In the Barcelona meeting it was agreed that the role of a GTPase in GTP catabolism would not be captured, need to confirm whether this would also remove GTP metabolism too. The additional AE information makes the annotation more complex than it needs to be
ATP1B1 ATP metabolic process GO:0046034 1/4 IDA (dependent_on GO:0031402 sodium ion binding, GO:0030955 potassium ion binding, GO:0016887 ATPase activity) ditto
ATP1A2 potassium ion import across plasma membrane GO:1990573 1/4 IC GO:0030955 potassium ion binding, GO:0016887 ATPase activity, GO:0016020 membrane
ATP1A2 cellular potassium ion homeostasis GO:0030007 1/4 IC GO:0030955 potassium ion binding, GO:0016887 ATPase activity, GO:0016020 membrane
ATP1A2 regulation of synaptic transmission, glutamatergic GO:0051966 1/4 NAS
ATP1A2 regulation of glutamate uptake involved in transmission of nerve impulse GO:0051946 1/4 NAS
ATP1A2 membrane repolarization GO:0086009 1/4 TAS (occurs_in UBERON_0000955, brain)
Cellular Component Annotations
ATP1A2 membrane GO:0016020 4/4 IDA all agreed
ATP1B1 membrane GO:0016020 4/4 IDA all agreed
ATP1A2 sodium:potassium-exchanging ATPase complex GO:0005890 1/4 IDA some discussion but if the sodium:potassium-exchanging ATPase activity annotation created then the binding data support this
ATP1B1 sodium:potassium-exchanging ATPase complex GO:0005890 1/4 IDA ditto