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Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents

Zhu, J and Davoli, T and Perriera, JM and Chin, CR and Gaiha, GD and John, SP and Sigiollot, FD and Gao, G and Xu, Q and Qu, H and Pertel, T and Sims, JS and Smith, JA and Baker, RE and Maranda, L and Ng, A and Elledge, SJ and Brass, AL (2014) Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents. Cell Reports. pp. 752-766.

Abstract

RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene's phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1-host cell interactions

Item Type: Article
Additional Information: NIBR author: Sigiollot, FD institute: NIBR contributor address: Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02127, USA.
Date Deposited: 13 Oct 2015 13:11
Last Modified: 13 Oct 2015 13:11
URI: https://oak.novartis.com/id/eprint/24923

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