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Project Achilles is a systematic effort aimed at identifying and cataloging gene essentiality across hundreds of genomically characterized cancer cell lines. Achilles uses genome-scale RNAi and CRISPR-Cas9 genetic perturbation reagents to silence or knockout individual genes and identify those genes that affect cell survival.
biomedical, genomics, health
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Project Achilles is a systematic effort aimed at identifying and cataloging gene essentiality across hundreds of genomically characterized cancer cell lines. It is part of the broader Cancer Dependency Map (DepMap) initiative at the Broad Institute.
Achilles uses genome-scale RNAi and CRISPR-Cas9 genetic perturbation reagents to silence or knockout individual genes and identify those genes that affect cell survival. By linking these dependencies to the genetic or molecular features of the tumors, this project is providing the foundation for the Cancer Dependency Map.
The project utilizes lentiviral-based pooled RNAi or CRISPR/Cas9 libraries in genome-scaled pooled loss-of-function (LOF) screening. This allows for the stable suppression of each gene individually in a subset of cells within a pooled format, enabling cost-effective genome-scale interrogation of gene essentiality.
Achilles has developed a highly standardized parallel screening workflow able to handle a large number of screens and ensure that the data across cell lines are comparable. Rigorous quality controls, including multiple cell line fingerprinting steps and monitoring of cell/reagent representation throughout the screening process, are performed to ensure the quality of the data.
The project has also developed computational methods to improve accuracy:
These methods computationally infer and subtract seed effects that arise for each shRNA, resulting in more reliable datasets.
Project Achilles is an ongoing effort aimed at screening more than 2000 cell lines of a variety of lineages, including cell lines derived from both solid and hematopoietic tumors of pediatric and adult lineages. The data is released on a quarterly basis pre-publication, with each release expanding the cell lines and genes covered.
The Achilles dataset enables researchers to:
The comprehensive nature of the dataset, covering hundreds of cell lines across diverse cancer types, makes it a valuable resource for cancer research and precision medicine.
Created: July 08, 2025 | Last modified: December 13, 2025