Comprehensive identification of host modulators of HIV-1 replication using multiple orthologous RNAi reagents
Name:
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UMass Chan Affiliations
Department of Quantitative Health SciencesDepartment of Microbiology and Physiological Systems
Document Type
Journal ArticlePublication Date
2014-10-23Keywords
Adaptor Proteins, Vesicular TransportAlgorithms
Carrier Proteins
Cell Cycle Proteins
HEK293 Cells
HIV-1
HeLa Cells
High-Throughput Screening Assays
*Host-Pathogen Interactions
HumansJurkat CellsNuclear Proteins*RNA Interference*Virus ReplicationAmino Acids, Peptides, and ProteinsBiochemistryCellular and Molecular PhysiologyComputational BiologyGenetics and GenomicsVirology
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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.Source
Cell Rep. 2014 Oct 23;9(2):752-66. doi: 10.1016/j.celrep.2014.09.031. Epub 2014 Oct 16. Link to article on publisher's site.DOI
10.1016/j.celrep.2014.09.031Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39785PubMed ID
25373910Notes
Full author list omitted for brevity. For the full list of authors, see article.
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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/3.0/Scopus Count
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Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
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