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10.1038/nbt.3834 http://scihub22266oqcxt.onion/10.1038/nbt.3834 C5557292!5557292 !28319085     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28319085 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Biotechnol 2017 ; 35 (5 ): 463-474 Nephropedia Template TP {{tp|p=28319085 |t=2017. Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions |pdf=|usr=}}{{28319085 }} gab.com Text Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions JO: Nat Biotechnol http://www.kidney.de/pget.php?&tw=1&pmid=28319085 #FOAvip Identification of effective combination therapies is critical to address the emergence of drug-resistant cancers, but direct screening of all possible drug combinations is infeasible. Here we introduce a CRISPR-based double knockout (CDKO) system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISPR-deleted gene pairs. We applied CDKO to generate a large-scale human GI map, comprising 490,000 double-sgRNAs directed against 21,321 pairs of drug targets in K562 leukemia cells and identified synthetic lethal drug target pairs for which corresponding drugs exhibit synergistic killing. These included the BCL2L1 and MCL1 combination, which was also effective in imatinib-resistant cells. We further validated this system by identifying known and previously unidentified GIs between modifiers of ricin toxicity. This work provides an effective strategy to screen synergistic drug combinations in high-throughput and a CRISPR-based tool to dissect functional GI networks. Twit Text FOAVip Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions ????Nat Biotechnol http://www.kidney.de/pget.php?&tw=1&pmid=28319085 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28319085 #FOAvip English Wikipedia <ref>{{Cite pmid|28319085 }}</ref> Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions #MMPMID28319085 Han K ; Jeng EE ; Hess GT ; Morgens DW ; Li A ; Bassik MC Nat Biotechnol 2017[May]; 35 (5 ): 463-474 PMID28319085 show ga Identification of effective combination therapies is critical to address the emergence of drug-resistant cancers, but direct screening of all possible drug combinations is infeasible. Here we introduce a CRISPR-based double knockout (CDKO) system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISPR-deleted gene pairs. We applied CDKO to generate a large-scale human GI map, comprising 490,000 double-sgRNAs directed against 21,321 pairs of drug targets in K562 leukemia cells and identified synthetic lethal drug target pairs for which corresponding drugs exhibit synergistic killing. These included the BCL2L1 and MCL1 combination, which was also effective in imatinib-resistant cells. We further validated this system by identifying known and previously unidentified GIs between modifiers of ricin toxicity. This work provides an effective strategy to screen synergistic drug combinations in high-throughput and a CRISPR-based tool to dissect functional GI networks. |Antineoplastic Combined Chemotherapy Protocols/*administration & dosage [MESH] |Clustered Regularly Interspaced Short Palindromic Repeats/*genetics [MESH] |Drug Screening Assays, Antitumor/*methods [MESH] |Drug Synergism [MESH] |Humans [MESH] |K562 Cells [MESH] |Neoplasm Proteins/*genetics [MESH]Synergistic drug combinations for cancer identified in a CRISPR screen(epmc).pdf DeepDyve Pubget Overpricing