High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

Channing Yu; Aristotle M. Mannan; Griselda Metta Yvone; Kenneth N. Ross; Yan Ling Zhang; Melissa A. Marton; Bradley R. Taylor; Andrew Crenshaw; Joshua Z. Gould; Pablo Tamayo; Barbara A. Weir; Aviad Tsherniak; Bang Wong; Levi A. Garraway; Alykhan F. Shamji; Michelle A. Palmer; Michael A. Foley; Wendy Winckler; Stuart L. Schreiber; Andrew L. Kung; Todd R. Golub

doi:10.1038/nbt.3460

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

Channing Yu, Aristotle M. Mannan, Griselda Metta Yvone, Kenneth N. Ross, Yan Ling Zhang, Melissa A. Marton, Bradley R. Taylor, Andrew Crenshaw, Joshua Z. Gould, Pablo Tamayo, Barbara A. Weir, Aviad Tsherniak, Bang Wong, Levi A. Garraway, Alykhan F. Shamji, Michelle A. Palmer, Michael A. Foley, Wendy Winckler, Stuart L. Schreiber, Andrew L. KungTodd R. Golub

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.

Original language	English (US)
Pages (from-to)	419-423
Number of pages	5
Journal	Nature Biotechnology
Volume	34
Issue number	4
DOIs	https://doi.org/10.1038/nbt.3460
State	Published - Apr 1 2016
Externally published	Yes

ASJC Scopus subject areas

Applied Microbiology and Biotechnology
Biotechnology
Molecular Medicine
Bioengineering
Biomedical Engineering

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10.1038/nbt.3460

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Yu, C., Mannan, A. M., Yvone, G. M., Ross, K. N., Zhang, Y. L., Marton, M. A., Taylor, B. R., Crenshaw, A., Gould, J. Z., Tamayo, P., Weir, B. A., Tsherniak, A., Wong, B., Garraway, L. A., Shamji, A. F., Palmer, M. A., Foley, M. A., Winckler, W., Schreiber, S. L., ... Golub, T. R. (2016). High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines. Nature Biotechnology, 34(4), 419-423. https://doi.org/10.1038/nbt.3460

Yu, C, Mannan, AM, Yvone, GM, Ross, KN, Zhang, YL, Marton, MA, Taylor, BR, Crenshaw, A, Gould, JZ, Tamayo, P, Weir, BA, Tsherniak, A, Wong, B, Garraway, LA, Shamji, AF, Palmer, MA, Foley, MA, Winckler, W, Schreiber, SL, Kung, AL & Golub, TR 2016, 'High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines', Nature Biotechnology, vol. 34, no. 4, pp. 419-423. https://doi.org/10.1038/nbt.3460

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abstract = "Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.",

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AU - Shamji, Alykhan F.

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High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

Abstract

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