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Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines

Joshua M. Dempster, Jordan Rossen, Mariya Kazachkova, Joshua Pan, Guillaume Kugener, David E. Root, View ORCID ProfileAviad Tsherniak
doi: https://doi.org/10.1101/720243
Joshua M. Dempster
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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  • For correspondence: dempster@broadinstitute.org
Jordan Rossen
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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Mariya Kazachkova
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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Joshua Pan
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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Guillaume Kugener
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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David E. Root
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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Aviad Tsherniak
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
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  • ORCID record for Aviad Tsherniak
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Abstract

One of the main goals of the Cancer Dependency Map project is to systematically identify cancer vulnerabilities across cancer types to accelerate therapeutic discovery. Project Achilles serves this goal through the in vitro study of genetic dependencies in cancer cell lines using CRISPR/Cas9 (and, previously, RNAi) loss-of-function screens. The project is committed to the public release of its experimental results quarterly on the DepMap Portal (https://depmap.org), on a pre-publication basis. As the experiment has evolved, data processing procedures have changed. Here we present the current and projected Achilles processing pipeline, including recent improvements and the analyses that led us to adopt them, spanning data releases from early 2018 to the first quarter of 2020. Notable changes include quality control metrics, calculation of probabilities of dependency, and correction for screen quality and other biases. Developing and improving methods for extracting biologically-meaningful scores from Achilles experiments is an ongoing process, and we will continue to evaluate and revise data processing procedures to produce the best results.

Footnotes

  • https://10.6084/m9.figshare.8061398

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 31, 2019.
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Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines
Joshua M. Dempster, Jordan Rossen, Mariya Kazachkova, Joshua Pan, Guillaume Kugener, David E. Root, Aviad Tsherniak
bioRxiv 720243; doi: https://doi.org/10.1101/720243
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Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines
Joshua M. Dempster, Jordan Rossen, Mariya Kazachkova, Joshua Pan, Guillaume Kugener, David E. Root, Aviad Tsherniak
bioRxiv 720243; doi: https://doi.org/10.1101/720243

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