Annotation Conf. Call 2016-02-08

From GO Wiki
Jump to navigation Jump to search

Agenda

Bluejeans Conference Line

Review New IGI Documentation

  • Following on from the 2016-01-12 call where we discussed how to annotate co-transfection experiments, below is a draft of new IGI documentation for curation.
  • For this call, I'd like to review the new documentation, and solicit input for examples.
  • For reference, here is the link to the existing documentation on the web site: http://geneontology.org/page/igi-inferred-genetic-interaction
    IGI: Inferred from Genetic Interaction
    •	Genetic interactions such as suppression, enhancement, synergistic (synthetic) interaction, etc.
    •	Co-transfection experiments
    •	Functional complementation
    •	Phenotypic rescue??  Formerly ‘Rescue experiments’. Does this refer to multicopy suppressors?
    •	Inference about one gene drawn from the phenotype of a mutation in a different gene??
 The IGI evidence code is used for annotations based on experiments reporting the effects of perturbations in the sequence or       
 expression of one or more genes or gene products.  IGI is also used for experiments that interrogate functional interactions 
 between two or more genes or gene products when co-expressed, for example, in a cell line.  Additional uses of IGI include 
 functional complementation experiments, genetic redundancy, phenotypic rescue (?), and inferences made about one gene drawn from 
 the phenotype of mutations in a different gene (?).  
 Key to deciding whether or not to use the IGI or IMP (Inferred from Mutant Phenotype) evidence code is consideration of the point
 of reference (i.e., what is being compared) to determine a possible interaction.  If experiments interrogate the effects of 
 multiple mutations or differences from the control, then use IGI.  If experiments interrogate the effects of a single mutation or 
 difference from the control, then use IMP.
 The IGI evidence code requires curators enter a stable database identifier for the interacting entity in the With/From field of the 
 Gene Association File (GAF).  Independent interactors may be captured in the With/From field by separating each entry with a pipe.  
 If the interaction experiment involves multiple perturbations simultaneously, e.g. triply mutant strains, then the respective 
 interactors are separated with a comma.
 Genetic interactions such as suppression, enhancement, synergistic (synthetic) interactions, etc.
 This use of the IGI evidence code refers to the more “traditional” genetic interaction experiments performed in model organisms, 
 such as Saccharomyces cerevisiae, as well as more recent approaches adopted in a number of different systems such as 
 RNA-mediated knockdown or genome editing techniques.  Note that genetic interaction experiments may be performed with both loss- 
 and gain-of-function mutations.  Consequently, curators will need to use their expertise to determine whether interaction 
 phenotypes resulting from gain-of-function mutations are informative about the normal, wild type role of a gene or gene product. 
 Example 1: Loss-of-function mutations
 Need example - David H. ?
 Example 2: Gain-of-function mutations  
 The response to axonal injury requires the activities of MAP kinase and cAMP signaling pathways that are required, for example, for 
 signaling growth cone formation.  In C. elegans, the activity of the upstream-most kinase in one of the MAPK signaling pathways, 
 DLK-1, is stimulated by Ca2+ influx mediated by the EGL-19 voltage-gated calcium channel.  EGL-19’s regulatory role in the 
 MAPK-mediated axon regeneration pathway was determined, in part, through doubly mutant animals containing an egl-19 gain-of-
 function mutation and a dlk-1 loss-of-function mutation that showed a reduced axon regenerative response when compared to    
 egl-19(gf) alone.  PMID:20203177
 EGL-19  positive regulation of MAPK cascade involved in axon regeneration (GO:1904922)  IGI  DLK-1
 Note that in this example, reciprocal IGI annotations are not made, as the GO term selected for EGL-19 does not make sense for 
 DLK-1.
 Example 3: Synergistic (synthetic) interactions
 Disruption of the MSB2 gene in S. cerevisiae has no appreciable effects on the cell's ability to activate the High-Osmolarity 
 Glycerol (HOG) pathway upon osmotic stress, or on cellular growth on high-osmolarity media.  To identify potential osmosensors in 
 the SHO1 branch of the HOG pathway, the authors screened for a mutant that is osmosensitive only in an msb2Δ background and 
 recovered mutations in the HKR1 gene.  Like MSB2, mutations in HRK1 alone confer no osmosensitivity to the cells.  PMID:17627274
 MSB2  hyperosmotic response (GO:0006972)  IGI  HKR1
 HKR1  hyperosmotic response (GO:0006972)  IGI  MSB2

Minutes