About Project Achilles

Project Achilles is a large collaboration between the Broad Institute and the Dana-Farber Cancer Institute to identify tumor vulnerabilities that are linked with predictive biomarkers. This is accomplished by performing genome-wide pooled shRNA screens across hundreds of cancer cell lines and then implementing an expanding suite of computational and analytical tools to derive biomarker-dependency relationships. Project Achilles leverages expertise from both biologist and computational scientists to create high quality essentiality datasets and rigorous analysis tools.

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Genome-wide interrogation of essentiality

The project aims at interrogating the essentiality of all human genes. The Broad RNAi platform has pioneered the use of lentiviral-based pooled shRNA libraries for genome-wide screening. This allows for the stable suppression of each gene individually in a subset of cells within a pooled format allowing for a cost-effective genome scale interrogation of gene essentiality. Rigorous quality controls, including multiple cell line fingerprinting steps, and monitoring of cell / hairpin representation through out the screening process are performed to ensure the quality of the data. The screening of the current published Achilles dataset (Achilles v2.0) was performed using a library of 54,020 shRNAs targeting 11,194 genes in quadruplicate. We are currently screening with a larger library of 96,771 shRNAs targeting 17,422 genes.

Hundreds of cell lines

Project Achilles is an ongoing effort aiming at screening >500 cell lines of a variety of lineages, including cell lines derived from both solid and hematopoietic tumors of pediatric and adult lineages. The use of multiple cell lines is critical to model the genomic diversity of human cancer and to accommodate imperfect correlation between genotype and phenotype. The current dataset, Achilles v2.0, contains data from 102 cell lines.

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Project team

Project Achilles is collaboration between the Hahn lab, Broad's RNAi platform and Broad's Cancer Program.

Lead Scientists
Glenn Cowley
Pablo Tamayo
Aviad Tsherniak
Francisca Vazquez
Barbara Weir

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