@article {1096116,
	title = {Improved detection of synthetic lethal interactions in Drosophila cells using variable dose analysis (VDA)},
	journal = {Proc Natl Acad Sci U S A},
	year = {2017},
	month = {2017 Nov 28},
	abstract = {Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets to specifically kill tumor cells, but this approach generally suffers from low consistency between screens. We found that many SS/L interactions involve essential genes and are therefore detectable within a limited range of knockdown efficiency. Such interactions are often missed by overly efficient RNAi reagents. We therefore developed an assay that measures viability over a range of knockdown efficiency within a cell population. This method, called Variable Dose Analysis (VDA), is highly sensitive to viability phenotypes and reproducibly detects SS/L interactions. We applied the VDA method to search for SS/L interactions with TSC1 and TSC2, the two tumor suppressors underlying tuberous sclerosis complex (TSC), and generated a SS/L network for TSC. Using this network, we identified four Food and Drug Administration-approved drugs that selectively affect viability of TSC-deficient cells, representing promising candidates for repurposing to treat TSC-related tumors.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1713362114},
	author = {Housden, Benjamin E and Li, Zhongchi and Kelley, Colleen and Wang, Yuanli and Hu, Yanhui and Valvezan, Alexander J and Manning, Brendan D and Perrimon, Norbert}
}
