IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13805-y.html
   My bibliography  Save this article

Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets

Author

Listed:
  • Joshua M. Dempster

    (Broad Institute of MIT and Harvard)

  • Clare Pacini

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Open Targets, Wellcome Genome Campus, Hinxton)

  • Sasha Pantel

    (Broad Institute of MIT and Harvard)

  • Fiona M. Behan

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Open Targets, Wellcome Genome Campus, Hinxton)

  • Thomas Green

    (Broad Institute of MIT and Harvard)

  • John Krill-Burger

    (Broad Institute of MIT and Harvard)

  • Charlotte M. Beaver

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Scott T. Younger

    (Broad Institute of MIT and Harvard)

  • Victor Zhivich

    (Broad Institute of MIT and Harvard)

  • Hanna Najgebauer

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Open Targets, Wellcome Genome Campus, Hinxton)

  • Felicity Allen

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Emanuel Gonçalves

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Rebecca Shepherd

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • John G. Doench

    (Broad Institute of MIT and Harvard)

  • Kosuke Yusa

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Kyoto University)

  • Francisca Vazquez

    (Broad Institute of MIT and Harvard)

  • Leopold Parts

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    University of Tartu)

  • Jesse S. Boehm

    (Broad Institute of MIT and Harvard)

  • Todd R. Golub

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

  • William C. Hahn

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

  • David E. Root

    (Broad Institute of MIT and Harvard)

  • Mathew J. Garnett

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Open Targets, Wellcome Genome Campus, Hinxton)

  • Aviad Tsherniak

    (Broad Institute of MIT and Harvard)

  • Francesco Iorio

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    Open Targets, Wellcome Genome Campus, Hinxton
    Human Technopole)

Abstract

Genome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyze data from recently published pan-cancer CRISPR-Cas9 screens performed at the Broad and Sanger Institutes. Despite significant differences in experimental protocols and reagents, we find that the screen results are highly concordant across multiple metrics with both common and specific dependencies jointly identified across the two studies. Furthermore, robust biomarkers of gene dependency found in one data set are recovered in the other. Through further analysis and replication experiments at each institute, we show that batch effects are driven principally by two key experimental parameters: the reagent library and the assay length. These results indicate that the Broad and Sanger CRISPR-Cas9 viability screens yield robust and reproducible findings.

Suggested Citation

  • Joshua M. Dempster & Clare Pacini & Sasha Pantel & Fiona M. Behan & Thomas Green & John Krill-Burger & Charlotte M. Beaver & Scott T. Younger & Victor Zhivich & Hanna Najgebauer & Felicity Allen & Ema, 2019. "Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13805-y
    DOI: 10.1038/s41467-019-13805-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13805-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13805-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Peter C. DeWeirdt & Abby V. McGee & Fengyi Zheng & Ifunanya Nwolah & Mudra Hegde & John G. Doench, 2022. "Accounting for small variations in the tracrRNA sequence improves sgRNA activity predictions for CRISPR screening," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Ruitong Li & Olaf Klingbeil & Davide Monducci & Michael J. Young & Diego J. Rodriguez & Zaid Bayyat & Joshua M. Dempster & Devishi Kesar & Xiaoping Yang & Mahdi Zamanighomi & Christopher R. Vakoc & Ta, 2022. "Comparative optimization of combinatorial CRISPR screens," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Gisele Nishiguchi & Lauren G. Mascibroda & Sarah M. Young & Elizabeth A. Caine & Sherif Abdelhamed & Jeffrey J. Kooijman & Darcie J. Miller & Sourav Das & Kevin McGowan & Anand Mayasundari & Zhe Shi &, 2024. "Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Ci Fu & Xiang Zhang & Amanda O. Veri & Kali R. Iyer & Emma Lash & Alice Xue & Huijuan Yan & Nicole M. Revie & Cassandra Wong & Zhen-Yuan Lin & Elizabeth J. Polvi & Sean D. Liston & Benjamin VanderSlui, 2021. "Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    5. Nishanth Ulhas Nair & Patricia Greninger & Xiaohu Zhang & Adam A. Friedman & Arnaud Amzallag & Eliane Cortez & Avinash Das Sahu & Joo Sang Lee & Anahita Dastur & Regina K. Egan & Ellen Murchie & Miche, 2023. "A landscape of response to drug combinations in non-small cell lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Natalia Baran & Alessia Lodi & Yogesh Dhungana & Shelley Herbrich & Meghan Collins & Shannon Sweeney & Renu Pandey & Anna Skwarska & Shraddha Patel & Mathieu Tremblay & Vinitha Mary Kuruvilla & Antoni, 2022. "Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13805-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.