A genome-wide loss-of-function screening method for minimizing false-negatives caused by functional redundancy
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Dear Editor,Loss-of-function screens are powerful tools for identifying gene contribution in a given biological context.Over the past decade,the RNA interference technology has become a dominant approach in the loss-of-function screen-based gene discovery ”1”.However,about 3 quarters of genes in mammalian genomes belong to gene families and have functional redundant homologs.While this functional redundancy protects cells and organisms from deleterious mutations ”2”,it also masks phenotypic outcomes,resulting in false-negatives in loss-of-function screens that target individual genes.However,all of reported loss-of-function screens have been designed to target individual genes and thus suffer from limitations of the false-negatives.
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The work was supported by the National Natural Science Foundation of China 31230044 and 31530094 to LL and the strategic priority research program of Chinese Academy of Sciences CAS;XDB19000000 to LL,NIH grant GM112182 to DW and the National Basic Research Program of China 973 Program;2011CB910204 to YL.