Improved detection of synthetic lethal interactions in Drosophila cells using variable dose analysis (VDA)

摘要: Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets 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 therefore detectable within limited range of knockdown efficiency. Such often missed by overly efficient RNAi reagents. developed an assay measures viability over efficiency cell population. This method, called Variable Dose Analysis (VDA), is highly sensitive phenotypes reproducibly detects interactions. applied the VDA method search for with TSC1 TSC2, two suppressors underlying tuberous sclerosis complex (TSC), generated network TSC. Using network, we identified four Food Drug Administration-approved drugs selectively affect TSC-deficient representing promising candidates repurposing treat TSC-related tumors.