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:0000109
 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:0000109 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:0000109, 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:0000105. 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:0000105 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?

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)
  • In what process does UNC-104 exhibit its function?
    • 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.
      • 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)
SYB-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"")"