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27-09-2017 | Image

Figure 4

Human synthetic lethality screens most commonly use either pairs of ‘matched’ or isogenic cell lines of the same background that have only the gene of interest mutated or inactivated (part a) or a panel of genetically diverse cell lines that are split into two groups depending on the status of the gene of interest (part b). After infection with a pool of lentivirus containing gene-specific small interfering RNAs (siRNAs) or single-guide RNAs (sgRNAs), cell populations are grown and next-generation sequencing technologies are used to identify sequences that are underrepresented (or ‘drop out’) solely in the cell line populations that are mutated or inactivated for the gene of interest. Genes targeted by multiple siRNAs or sgRNAs in this subset are candidate synthetic lethal (SL) partners for the gene of interest.