Systematic Functional Annotation of the 2016 Yeast Genetic Interaction Network
summary
Introduces the SAFE method that turns the 2016 yeast genetic interaction similarity network into a spatial analysis of functional enrichment by defining layout-based local neighborhoods, running hypergeometric tests against ~4,000 GO terms, and correcting p values. Finds ~500 GO terms that are region-specific, collapses enrichment into 19 regions automatically, and validates with 132 drug screens showing known targets (doxorubicin, bortezomib) and a novel Golgi–proteasome resistance link recapitulated by genetic interactions; code and apps are provided.
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chapters (16)
- 0:00Intro
- 0:15Networks as maps of biological systems
- 2:46Genetic interactions
- 6:05Similarity of genetic interaction profiles
- 8:30Genetic interaction similarity network (year 2010)
- 11:34The Yeast Genetic Interaction Similarity Network (Year 2016)
- 13:12Spatial Analysis of Functional Enrichment (SAFE)
- 16:05Different GO terms show different patterns of enrichment
- 18:37Related processes = similar patterns of enrichment
- 20:17The Automated Functional Map of the Yeast Genetic Interaction Similarity Network
- 20:49SAFE is sensitive & robust to biological signal
- 21:51The chemical genomic advantage
- 23:16SAFE recapitulates the known modes-of- action of chemical compounds
- 24:17SAFE uncovers potentially novel mechanisms of drug activity
- 25:59Could it be a side effect of bortezomib?
- 27:55Acknowledgements
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