Improved detection of synthetic lethal interactions in Drosophila cells using variable dose analysis (VDA)
Abstract
Synthetic sick or lethal (SS/L) interactions occur when disruption of two genes reduces cell viability to a greater extent than expected based on the individual gene disruptions. SS/L interactions involving tumor suppressors represent candidate drug targets for cancers because treatment is expected to kill tumor cells carrying the tumor suppressor mutation but leave healthy cells unaffected. Identification of SS/L interactions is of vital importance to develop new therapies for tumorigenic disease. We have developed an RNAi-based approach called variable dose analysis, which improves both sensitivity and robustness to noise compared with dsRNA-based methods for screening in Drosophila . Using this method, we identified four Food and Drug Administration-approved drugs with specific effects on cells deficient for the TSC1 and TSC2 tumor suppressor genes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 28, 2017
- Source ID
- 10.1073/pnas.1713362114
Entities
People
- Alexander J. Valvezan
- Benjamin E Housden
- Brendan D Manning
- Colleen Kelley
- Norbert Perrimon
- Yanhui Hu
- Yuanli Wang
- Zhongchi Li
Organizations
- Harvard Medical School
- Howard Hughes Medical Institute
- National Institutes of Health
- United States Department of Defense
- University of Exeter
- University of Pennsylvania