Annotation Conf. Call, July 28, 2015

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Agenda

Overview by ontology editors

Why certain relations were going to be obsoleted

Example papers

Obsoleted relationship:
independent_of
PMID:25215947
Typically mitophagy is dependent on PARK2 / parkin (Uniprot O60260). However, in PMID:25215947, authors show that AMBRA1 (Q9C0C7) (in presence of chemical inducers of mitochondrial depolarisation such as FCCP) initiates mitophagy independent of PARK2 / parkin. What to do now that independent_of relation is obsoleted? Simplest to create new term instead? e.g. “parkin-independent mitophagy in response to mitochondrial depolarization”.
NB Examples of parkin-independent mitophagy:
PMID: 25349190 "Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain."
PMID: 24176932 "Loss of iron triggers PINK1/Parkin-independent mitophagy."
Paul Denny, UCL Functional Annotation Group.

in_absence_of
Q75JZ1 gtaC
annotation: nucleus in_absence_of cAMP
PMID:24653039
Title of paper: Nucleocytoplasmic Shuttling of a GATA Transcription Factor Functions as a Development Timer. “We report here that GtaC exhibits rapid nucleocytoplasmic shuttling in response to periodic cAMP waves.” p1329
COMMENT: This was annotated in conjunction with a current ‘cytosol in_presence _of cAMP’ annotation. No other annotations would describe the shuttling as well as these two annotations together and in further conjunction with the annotation: regulation of aggregation involved in sorocarp development dependent_on cellular protein localization

in_presence_of
Q550R2 ctxB
positive regulation of gene expression has_regulation_target carA, acaA, rasG,rasC, in_presence_of cAMP
PMID:22114350
FIGURE 6: Inhibition of cAMP-activation of Ras in ctxA−/B− cells. (A) cAMP activation of RasC and G.
FIGURE 5: Cortexillin-null cells have delayed and diminished expression of cAR1 and ACA. Suspensions of WT and cortexillin-null cells in starvation buffer were pulsed with cAMP…. ctxA− and ctxB− cells had delayed and reduced expression of ACA and cAR1, and ctxA−/B− cells had almost no expression of either ACA or cAR1.
COMMENT: Even though in Fig. 6 authors mention ‘cAMP activation, I like in_presence_of’ as it implies the correct thing; dependent_on implies that the regulation of the gene expression is dependent of cAMP, but it’s really dependent on the mutated gene(s) shown in this study. The addition of cAMP is mimicking natural starvation induced behaviour and in the assay they used cAMP. A more interpretive annotation would be:
positive regulation of gene expression has_regulation_target carA, acaA, rasG,rasC, happens_during response to starvation. Here the user must know what happens during starvation and it is more my interpretation than annotating what actually happens where users can interpret.

Q54BD4 dstC
response to cation stress happens_during sorocarp development in_presence_of potassium chloride
PMID: 22944283
There are four such annotations made for all 4 tested stress factors that resulted in developmental defects.
p.793: we investigated the development under stress of the dstC− (STATc) mutant. The dstC− mutant showed severe defects with fewer and/or smaller fruiting bodies under all of the stressing conditions (KCl, NaCl, MgCl2, LiCl) FIGURE 6. TacA is involved in the stress response during development.
COMMENT: Here it feels not appropriate to replace in_presence_of with ‘dependent_on’ and I would have lots of gripes against using ‘has_input’. Not clear what ‘has_agent’ means, never used that and wouldn’t like it either in this context.
Petra Fey, dictyBase