Variable dose analysis: A novel RNAi-based method for detection of synthetic lethal interactions
作者： Benjamin E. Housden , Zhongchi Li , Colleen Kelley , Yuanli Wang , Yanhui Hu
DOI: 10.1101/176974
关键词:
摘要: Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets specifically kill tumor cells but such generally suffer from low reproducibility. 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 this network, we identified four FDA-approved drugs selectively affect TSC deficient cells, representing promising candidates repurposing treat TSC-related tumors.
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