Annotation Conf. Call, July 14, 2015
New ECO term for inferencing pipeline
The InterOntology inferencing pipeline will get new ECO terms.
- The 2 first codes would distinguish between annotations inferred from manual and automated annotations:
- evidence based on logical inference from manual annotation used in automatic assertion - evidence based on logical inference from electronic annotation used in automatic assertion Both terms belong in the "automatic assertion" part of the ontology, and should be descendants of ECO:0000501, because the pipeline that generates the inferred annotations is an automatic one.
The third code, "evidence based on logical inference used in automatic assertion", would be a parent of the other two. Adding such a parent, though it would not be used directly in the annotations themselves, would make it easier for processing the rules in the eco-usage-constraints  file (which associates evidence codes with the values allowed in the with_string): we'd have only one entry in the file and the rule would be automatically propagated to the subclasses.
- IEA will be used in regular GAFs and ECO in the GPAD. The GOID that was used for the inference will be in the With/From column for the IEAs
- Once the ECO term is available the scripts that generate these inferences will make this change. There will be enough notice!
Tracker to follow- https://github.com/evidenceontology/evidenceontology/issues/49
New Term Genie templates
Two new templates are now ready to use in the TermGenie (TG) tool to request new GO terms:
Template: macromolecular complex binding; Description: binding of a macromolecular complex
Template: cellular component organization; Description: organization of a cellular component
These templates can be found using the text search box, or expanding the 'Molecular Function' or 'Processes' tree respectively.
miRNA guidelines (Rachael and others)
Note: The guidelines don't only cover annotation of miRNAs but also annotation of proteins involved in the miRNA biogenesis pathway! (e.g. Dicer, Drosha etc.)
use of 'regulation of activity' (UCL group)
'QUESTION: Would you annotate a protein involved in localisation (or regulation of localisation) of X to ‘regulation of X activity’ ?'
Case 1: ION CHANNELS
In response to stimuli, ion channels are localised within the neuron to increase synaptic transmission, membrane potential etc.
Would you annotate the GPs that regulate this localization or directly localize ion channels to:
- regulation of cation channel activity ; GO:2001257
- regulation of cation transmembrane transport ; GO:1904062
Case 2: TRANSCRIPTION FACTORS
Would you annotate factors that shuttle TFs into the nucleus, or the upstream signals that regulate the shuttling to:
- regulation of sequence-specific DNA binding transcription factor activity ; GO:0051090’
- regulation of transcription from RNA polymerase II promoter ; GO:0006357
See PMID: 8851662 for different mechanisms of modulating TF localisation
Case 3: TRANSPORTERS
Would you annotate GPs that localise a transporter (or regulate localisation of a transporter) to 'regulation of transporter activity’?
GLUT4 is sequestered in intracellular vesicles. In response to insulin, GLUT4 is translocated to the plasma membrane where GLUT4 transporters are inserted and become available for transporting glucose. Thus glucose uptake is regulated by controlling the number of GLUT4 transporters on the cell surface.
Would you annotate the GPs involved in regulating GLUT4 translocation to:
- regulation of transporter activity ; GO:0032409
- regulation of transport ; GO:0051049
In this case, the signaling components are regulating the localisation of GLUT4.
Case 4: KINASES
Would you annotate GPs that localise a kinase to a specific place in the cell to:
- regulation of kinase activity ; GO:0043549
- regulation of phosphorylation ; GO:0042325
The regulatory subunits of some kinases, for instance (e.g. PI3K), are involved in trafficking the catalytic kinase to the site of its substates.
We will discuss some of the relations (mostly used for Col-16) that have been slated for obsoletion. They are:
in_presence_of in_absence_of, independent_of
If you have examples (papers) where you have used them, please add it to the agenda for the next call.
New ECO term
There were no concerns about this new term. Once Marcus creates the terms/commits them, all the downstream processes will take into effect (changes to scripts etc). Stay tuned.
Suzi and Paul T will talk to Rachael about the terms/annotations.
use of 'regulation of activity' (UCL group)
It was discussed and agreed that it is inappropriate to use 'regulation of activity of X' for proteins that localize or regulate the localization of X.
There was further discussion about whether 'regulation of X process' was an appropriate annotation for these factors. Current GO terms such as 'positive regulation of transcription by transcription factor localization ; GO:0061586' provide support that these steps upstream of transcription are regulating transcription. Also, members of the upstream signaling pathway are considered to regulate transcription.
Suzi suggested the use of 'causally_upstream_of:transcription' relation in C16 to further capture the order of bioliogical events. It was decided that specific examples were needed to discuss at LEGO calls. Therefore Ruth has suggested the following papers on ion channels (the case that sparked this originally query).
- Ank3 (Ankyrin-G) O70511
- Cardiomyocytes with reduced ankyrin-G display reduced Na(v)1.5 expression, abnormal Na(v)1.5 membrane targeting, and reduced Na(+) channel current density. These data are the first report of a cellular pathway required for Na(v) channel trafficking in the heart and suggest that ankyrin-G is critical for cardiac depolarization and Na(v) channel organization in multiple excitable tissues.
- ANK3 decreases Kv1.1 activity
- To examine whether the Kv1.1-interacting candidate ANK3 could modulate the channel function, we used the whole-cell patch-clamp technique in human embryonic kidney 293 (HEK293) cells transiently transfected with both proteins. Activation of the ion channel via the application of a series of depolarizing voltage steps elicited outward rectifying currents resembling the main biophysical characteristics of Kv1.1, that is, a fast delayed activation and slowly inactivating kinetics. These currents were absent in mock-transfected HEK293 cells (Figure 2a). Cells were clamped at a holding potential of −80 mV, and currents were elicited by the application of a family of voltage steps in 200-ms intervals, from −80 mV to +50 mV in 10-mV increments. Tail currents were recorded at −80 mV by using a high K+ extracellular solution. Coexpression of ANK3 produced a significant reduction of the outward currents mediated by Kv1.1, when depolarizing voltage steps were applied
- RNF207 Q6ZRF8
- This paper suggests that RNF207 regulates the ‘activity' of human ether-a-go-go-related gene (HERG) potassium channel: RNF207 is an important regulator of action potential duration, likely via effects on HERG trafficking and localization in a heat shock protein-dependent manner.