Annotation Conf. Call 2016-03-22

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Bluejeans

Agenda

IC from ISS

  • From 2016-03-08 annotation call, we agreed that IC annotations from existing ISS annotations would be okay, but would require a new GO_REF to document the annotation practice.
    • Rebecca drafted the text of the new GO_REF:
 GO_REF:0000111
 title: Gene Ontology annotations Inferred by Curator (IC) using at least one Inferred by Sequence Similarity (ISS) annotation to 
 support the inference
 year: 2016
 The Gene Ontology Consortium uses the IC (Inferred by Curator) evidence code when assignment of a GO term cannot be supported by 
 direct experimental or sequence-based evidence, but can, based on a curator’s biological knowledge, be reasonably inferred from 
 existing GO annotations to the same gene/gene product.  Use of the IC evidence code with GO_REF:0000111 indicates that a curator 
 inferred the GO term based on at least one supporting annotation with an ‘Inferred from Sequence Similarity’ (ISS) evidence code.  
 Note that additional supporting annotations may be experimentally evidenced. When using GO_REF:0000111, the 'with/from' field must 
 contain all GO identifiers used as supporting annotations.
  • As well as a proposed update to the GO website documentation:
 In cases where the GO term is inferred from sequence similarity evidence, such IC-annotations will use reference GO_REF:0000111. When 
 using this reference, one or more supporting annotations will be ISS-evidenced; a supporting ISS-evidenced annotation may also be used 
 together with a experimentally-evidenced supporting annotation (e.g. IDA or IMP).
 GO_REF:0000111 can be used where the supporting ISS annotations are transferred from different species. For example, an IC-evidenced 
 GO term can be created for a human protein based on two different GO terms; one ISS'd from mouse to human, and one ISS'd from rat to 
 human.

Use of has_participant Annotation Extension Relation

  • Definition: Identifies an entity affected by the gene product's participation in a molecular function or biological process
  • has_participant documention on GO wiki
  • Okay to use this annotation extension relation when it is capturing legacy information?
    • In MGI we captured thousands of annotations where a term was associated with an anatomical structure before the method of using relations was in place. In these cases, we know that the structure somehow participates in the process, but we don't know exactly how. We would like to allow these annotations extensions to pass the checks.

http://amigo.geneontology.org/amigo/gene_product/MGI:MGI:1276112

  • Would it be possible to allow our legacy annotations, but have the rule that this relation should not be used for new manual annotations?
  • [Addition by Rachael] There has been the suggestion to use has_participant to indicate cell types for cell-cell type terms, e.g. cell-cell adhesion.

I see problems with this and it hasn't yet reached a resolution. See GitHub: https://github.com/geneontology/annotation_extensions/issues/61 Any suggestions?

Annotation Consistency Exercise

 Kinesin-3 motor UNC-104/KIF1A is essential for transporting synaptic precursors to synapses. Although the mechanism of cargo binding 
 is well understood, little is known how motor activity is regulated. We mapped functional interaction domains between SYD-2 and 
 UNC-104 by using yeast 2-hybrid and pull-down assays and by using FRET/fluorescence lifetime imaging microscopy to image the binding 
 of SYD-2 to UNC-104 in living Caenorhabditis elegans. We found that UNC-104 forms SYD-2-dependent axonal clusters (appearing during 
 the transition from L2 to L3 larval stages), which behave in FRAP experiments as dynamic aggregates. High-resolution microscopy 
 reveals that these clusters contain UNC-104 and synaptic precursors (synaptobrevin-1). Analysis of motor motility indicates 
 bi-directional movement of UNC-104, whereas in syd-2 mutants, loss of SYD-2 binding reduces net anterograde movement and velocity 
 (similar after deleting UNC-104's liprin-binding domain), switching to retrograde transport characteristics when no role of SYD-2 on 
 dynein and conventional kinesin UNC-116 motility was found. These data present a kinesin scaffolding protein that controls both motor 
 clustering along axons and motor motility, resulting in reduced cargo transport efficiency upon loss of interaction.
  • What is UNC-104's function?
    • ATP-dependent microtubule motor activity, plus-end-directed (GO:0008574)
  • What is SYD-2's function?
    • kinesin binding (GO:0019894)
    • protein binding, bridging (GO:0030674)
  • In what process does UNC-104 exhibit its function?
    • synaptic vesicle transport (GO:0048489) - The directed movement of synaptic vesicles.
      • axo-dendritic transport (GO:0008088) - The directed movement of organelles or molecules along microtubules in neuron projections.
        • anterograde axonal transport (GO:0008089) - The directed movement of organelles or molecules along microtubules from the cell body toward the cell periphery in nerve cell axons.
          • anterograde synaptic vesicle transport (GO:0048490) - The directed movement of synaptic vesicle along axonal microtubules from the cell body to the presynapse.
  • In what process does SYD-2 exhibit its function?
    • regulation of microtubule motor activity (GO:2000574) - Any process that modulates the frequency, rate or extent of microtubule motor activity.
      • positive regulation of ATP-dependent microtubule motor activity, plus-end-directed (GO:2000582) - Any process that activates or increases the frequency, rate or extent of ATP-dependent microtubule motor activity, plus-end-directed.
    • regulation of microtubule-based movement (GO:0060632) - Any process that modulates the rate, frequency, or extent of microtubule-based movement, the movement of organelles, other microtubules and other particles along microtubules, mediated by motor proteins.
      • positive regulation of anterograde synaptic vesicle transport (GO:1903744) - Any process that activates or increases the frequency, rate or extent of anterograde synaptic vesicle transport.
    • regulation of vesicle-mediated transport - (GO:0060627) - Any process that modulates the rate, frequency, or extent of vesicle-mediated transport, the directed movement of substances, either within a vesicle or in the vesicle membrane, into, out of or within a cell.
      • positive regulation of synaptic vesicle transport (GO:1903744) - Any process that activates or increases the frequency, rate or extent of synaptic vesicle transport.
        • NEW TERM: positive regulation of anterograde transport or positive regulation of anterograde axon cargo transport
    • protein localization (GO:0008104) - Any process in which a protein is transported to, or maintained in, a specific location.
      • protein localization to axon (GO:0099612) - A process in which a protein is transported to or maintained in a location within an axon.
  • Annotation Issues
    • Protein binding - traditional GO annotation vs LEGO-style annotation using has_input (or has_direct_input) annotation extensions
    • Protein binding - always need reciprocal annotations?
    • Use of annotation extensions to provide context for SYD-2's regulatory role
    • What relation is appropriate for regulation of UNC-104's motor activity?
    • What relation is appropriate for regulation of the transport process that UNC-104 mediates?
    • Protein localization for motor proteins or other entities that move through a subcellular region - are they part_of that region or is there another relation that more accurately captures their dynamic localization?


Gene/Marker Name GO term Evidence Code With/From Annotation Extension Annotation Extension Annotation Extension Annotation Extension Comment
SYD-2 kinesin binding (GO:0019894) IPI UNC-104
UNC-104 protein binding (GO:0005515) IPI SYD-2
SYD-2 protein binding (GO:0005515) IPI UNC-104
UNC-104 protein binding (GO:0005515) IPI SYD-2
SYD-2 kinesin binding (GO:0019894) IDA has_input (UNC-104) occurs_in (dendrite GO:0030425) occurs_in (head neuron WBbt:0006751)
UNC-104 protein binding (GO:0005515) IPI SYD-2 occurs_in (dendrite GO:0030425) occurs_in (head neuron WBbt:0006751)
SYD-2 kinesin binding (GO:0019894) IDA has_direct_input (UNC-104)
SYD-2 kinesin binding (GO:0019894) IDA has_input (UNC-104) part_of (protein binding, bridging GO:0030674)
UNC-104 ATP-dependent microtubule motor activity, plus-end-directed (GO:0008574) IDA
SYD-2 positive regulation of ATP-dependent microtubule motor activity, plus-end-directed (GO:2000582) IMP has_regulation_target (UNC-104)
SYD-2 positive regulation of ATP-dependent microtubule motor activity, plus-end-directed (GO:2000582) IMP directly_activates (UNC-104)
SYD-2 regulation of microtubule motor activity (GO:2000574) IMP regulates_o_enabled_by (UNC-104) occurs_in (neuron WBbt:0003679)
SYD-2 regulation of microtubule motor activity (GO:2000574) IDA has_regulation_target (UNC-104)
UNC-104 anterograde synaptic vesicle transport (GO:0048490) IDA
UNC-104 anterograde axonal transport (GO:0008089) IDA Didn't chose anterograde synaptic vesicle transport as not what I want to transport. new term? "anterograde synaptic vesicle protein transport vesicle transport" (note definition of "synaptic vesicle protein transport vesicle ; GO:0097547" vs " synaptic vesicle ; GO:0008021) or "anterograde axon cargo transport "
SYD-2 regulation of microtubule-based movement (GO:0060632) IGI UNC-104
SYD-2 positive regulation of anterograde synaptic vesicle transport (GO:1903744) IMP occurs_in (neuron WBbt:0003679)
SYD-2 positive regulation of anterograde synaptic vesicle transport (GO:1903744) IDA has_regulation_target (UNC-104)
SYD-2 NEW TERM: positive regulation of anterograde transport or positive regulation of anterograde axon cargo transport IMP has_regulation_target (UNC-104)
SYD-2 protein localization (GO:0008104) IMP has_input (UNC-104) occurs_in (neuron WBbt:0003679)
SYD-2 protein localization to axon (GO:0099612) IMP has_direct_input (UNC-104)
UNC-104 axo-dendritic transport (GO:0008088) IDA occurs_in (neuron WBbt:0003679)
DLC-1 axo-dendritic transport (GO:0008088) IDA occurs_in (neuron WBbt:0003679)
UNC-116 axo-dendritic transport (GO:0008088) IDA occurs_in (neuron WBbt:0003679)
UNC-104 axon (GO:0030424) IMP happens_during (larval development)
SNB-1 synapse (GO:0045202) IDA
  • Other comments: "Not inclined to annotate the regulation of clustering as it is not entirely clear what these clusters are - "These results provide evidence that UNC-104 cluster are dynamic membranous structures to which motors can accumulate (from suppl ""possibly serving as an active motor pool) and eventually move along the neurite. Interestingly, clusters are not solely stationary motor deposits, as we also occasionally observe whole clusters moving"")"

Minutes

  • On call:
    • Berkeley: Chris, Suzi
    • dictyBase - Petra
    • EBI: Aleks, Alex, Melanie, Paola, Tony
    • FlyBase: Giulia, Helen
    • MGI: David H.
    • RGD: Shur-Jen, Stan
    • SGD: Edith, Stacia
    • TAIR: Tanya
    • UCL: Rachael, Rebecca, Ruth
    • WB: Kimberly
    • Zfin: Sabrina

IC from ISS

  • Reviewed new GO_REF:0000111 and updates to website documentation
  • No objections to either - will go forward with new GO_REF and curation doc
  • Tony updated Protein2GO to reflect the new annotation policy and use of GO_REF:0000111

Use of has_participant Annotation Extension Relation

  • This discussion was precipitated by loss of information when MGI annotations are loaded into GOA database
  • Current annotation practice does not allow use of has_participant annotation extension relation, but this is the relation that MGI used to populate a lot of legacy information about, for example, anatomy, cell type, etc.
  • Can we allow this relation to be used for legacy data but not for new annotations by using something like a time stamp?
  • Could has_participant be valid for display but not future curation?
  • has_participant was proposed as the appropriate relation to use for a term like cell-cell adhesion, so this would mean it is okay for future use
  • We discussed the merits of having a more specific child term of has_participant for terms like cell-cell adhesion
  • Semantically, a more specific relation may not add anything, but more specific relations might help curators decide what is the appropriate relation to use
  • Could rules be formulated in the GO_rel file to indicate how specific annotation extension relations can be used?

Annotation Consistency Exercise

  • Exercise highlighted different ways of capturing protein binding information in traditional GO annotation (IPI and use of With/From column) vs LEGO annotation (use of annotation extension has_input(entity))
    • GO protein binding annotations are used to construct interaction networks, but this work was done assuming that all protein binding annotations would use IPI and the With/From column
    • If there is an alternative way of capturing this information, we need to make sure we're accounting for that in the network representation through a union of both types of annotation
    • This issue needs review and a policy decision
    • Are there advantages/disadvantages to making the annotations one way or another?
  • Annotations to SYD-2 - how to accurately reflect its role in regulating UNC-104/kinesin activity
    • Did the experiments demonstrate a change in UNC-104 activity in the presence of SYD-2 or did they demonstrate that SYD-2 increased the rate of synaptic vesicle transport because it clustered more UNC-104 on vesicles?
    • Will work on modeling this paper in LEGO to see how we can represent the roles of each gene product
    • This paper gets at the difference between annotations that reflect the mechanism by which a gene product accomplishes something vs its actual function
    • A similar annotation issue has come up with the synapse group wrt postsynaptic receptor abundance - if a gene product such as a transcription factor regulates the number of receptors does it regulate the activity associated with those receptors, or just the signaling process mediated by those receptors?