Annotation Conf. Call 2016-03-22
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?
- [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)
- 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.
- 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.
- axo-dendritic transport (GO:0008088) - The directed movement of organelles or molecules along microtubules in neuron projections.
- synaptic vesicle transport (GO:0048489) - The directed movement of synaptic vesicles.
- 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
- positive regulation of synaptic vesicle transport (GO:1903744) - Any process that activates or increases the frequency, rate or extent of synaptic vesicle 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.
- regulation of microtubule motor activity (GO:2000574) - Any process that modulates the frequency, rate or extent of microtubule motor activity.
- 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"")"