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- W2745996918 abstract "Abstract Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets to specifically kill tumor cells but such screens generally suffer from low reproducibility. 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 FDA-approved drugs that selectively affect viability of TSC deficient cells, representing promising candidates for repurposing to treat TSC-related tumors." @default.
- W2745996918 created "2017-08-31" @default.
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- W2745996918 date "2017-08-16" @default.
- W2745996918 modified "2023-09-24" @default.
- W2745996918 title "Variable dose analysis: A novel RNAi-based method for detection of synthetic lethal interactions" @default.
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- W2745996918 doi "https://doi.org/10.1101/176974" @default.
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