Summary
Develop computational methods to understand drug response mechanisms and sources of variation, including genetic and epigenetic factors, to enable more precise drug therapies.
Computational methods for characterizing sources of variability in drug response
US · IL
NIH
grant
open
#nih-5R35GM153195-02
What they want
The project aims to address the incomplete understanding of drug mechanisms, genetic/epigenetic impacts, and phenotypic responses that lead to reduced efficacy and adverse events. It will leverage abundant data (human genetic variation, gene expression, protein 3D structures, biobanks, EMR, FDA databases) using computational/statistical approaches. The work will focus on answering five driving questions: the full set of clinical responses to drugs, molecular off-targets modulated by a drug, pathways modulating drug response, how genetic variation in targets/pathways leads to variation, and how epigenetics create variability in drug response.
Deliverables
- Computational methods
- Validated novel hypotheses
Technical requirements
- Computational/statistical approaches that integrate data at all scales
- Use of publicly available data
How they evaluate
- Methods evaluated with independent, held-out gold standard data sets (to establish quantitative statistical performance)
- Collaboration with experimental colleagues to validate key novel hypotheses
