Abstract
Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for non-small cell lung cancer treatments. TCGI has dramatically improved the current methods for mapping genetic interactions and screening drug targets for combinational therapies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Animals
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CRISPR-Cas Systems / genetics
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Survival / genetics
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Chromosome Mapping
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Epistasis, Genetic / genetics
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Genome, Human / genetics
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HEK293 Cells
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Humans
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Myeloid Cell Leukemia Sequence 1 Protein / genetics*
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RNA, Transfer / genetics
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Trans-Activators / genetics*
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Transcription Factors / genetics*
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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MCL1 protein, human
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Myeloid Cell Leukemia Sequence 1 Protein
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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WWTR1 protein, human
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YAP-Signaling Proteins
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YAP1 protein, human
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RNA, Transfer