Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level & Reveals an Unprecedented Enrichment in Pooled ShRNA Screens.

Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level & Reveals an Unprecedented Enrichment in Pooled ShRNA Screens.
Comb Chem High Throughput Screen. 2013 Jul 8;
Authors: Bhinder B, Djaballah H
Abstract
RNA interference (RNAi) has opened promising avenues to better understand gene function. Though many RNAi screens report on the identification of genes, very few, if any, have been further studied and validated. Data discrepancy is emerging as one of RNAi main pitfalls. We reasoned that a systematic analysis of lethality-based screens, since they score for cell death, would examine the extent of hit discordance at inter-screen level. To this end, we developed a methodology for literature mining and overlap analysis of several screens using both siRNA and shRNA flavors, and obtained 64 gene lists censoring an initial list of 7,430 nominated genes. We further performed a comparative analysis first at a global level followed by hit re-assessment under much more stringent conditions. To our surprise, none of the hits overlapped across the board even for PLK1, which emerged as a strong candidate in siRNA screens; but only marginally in the shRNA ones. Furthermore, EIF5B emerges as the most common hit only in the shRNA screens. A highly unusual and unprecedented result was the observation that 5,269 out of 6,664 nominated genes (~80%) in the shRNA screens were exclusive to the pooled format, raising concerns as to the m...

Source: Combinatorial Chemistry and High Throughput Screening - July 8, 2013 Category: Chemistry Authors: Bhinder B, Djaballah H Tags: Comb Chem High Throughput Screen Source Type: research