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A comprehensive Bioconductor ecosystem for the design of CRISPR guide RNAs across nucleases and technologies

Author

Listed:
  • Luke Hoberecht

    (Genentech Research and Early Development, Genentech, Inc.)

  • Pirunthan Perampalam

    (ProCogia Inc. under contract to Hoffmann-La Roche Limited)

  • Aaron Lun

    (Genentech Research and Early Development, Genentech, Inc.)

  • Jean-Philippe Fortin

    (Genentech Research and Early Development, Genentech, Inc.)

Abstract

The success of CRISPR-mediated gene perturbation studies is highly dependent on the quality of gRNAs, and several tools have been developed to enable optimal gRNA design. However, these tools are not all adaptable to the latest CRISPR modalities or nucleases, nor do they offer comprehensive annotation methods for advanced CRISPR applications. Here, we present a new ecosystem of R packages, called crisprVerse, that enables efficient gRNA design and annotation for a multitude of CRISPR technologies. This includes CRISPR knockout (CRISPRko), CRISPR activation (CRISPRa), CRISPR interference (CRISPRi), CRISPR base editing (CRISPRbe) and CRISPR knockdown (CRISPRkd). The core package, crisprDesign, offers a user-friendly and unified interface to add off-target annotations, rich gene and SNP annotations, and on- and off-target activity scores. These functionalities are enabled for any RNA- or DNA-targeting nucleases, including Cas9, Cas12, and Cas13. The crisprVerse ecosystem is open-source and deployed through the Bioconductor project ( https://github.com/crisprVerse ).

Suggested Citation

  • Luke Hoberecht & Pirunthan Perampalam & Aaron Lun & Jean-Philippe Fortin, 2022. "A comprehensive Bioconductor ecosystem for the design of CRISPR guide RNAs across nucleases and technologies," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34320-7
    DOI: 10.1038/s41467-022-34320-7
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    1. Johnny H. Hu & Shannon M. Miller & Maarten H. Geurts & Weixin Tang & Liwei Chen & Ning Sun & Christina M. Zeina & Xue Gao & Holly A. Rees & Zhi Lin & David R. Liu, 2018. "Evolved Cas9 variants with broad PAM compatibility and high DNA specificity," Nature, Nature, vol. 556(7699), pages 57-63, April.
    2. Summer B. Thyme & Laila Akhmetova & Tessa G. Montague & Eivind Valen & Alexander F. Schier, 2016. "Internal guide RNA interactions interfere with Cas9-mediated cleavage," Nature Communications, Nature, vol. 7(1), pages 1-7, September.
    3. 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.
    4. Kendall R. Sanson & Ruth E. Hanna & Mudra Hegde & Katherine F. Donovan & Christine Strand & Meagan E. Sullender & Emma W. Vaimberg & Amy Goodale & David E. Root & Federica Piccioni & John G. Doench, 2018. "Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    5. Yihan Zhang & Wei Qin & Xiaochan Lu & Jason Xu & Haigen Huang & Haipeng Bai & Song Li & Shuo Lin, 2017. "Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system," Nature Communications, Nature, vol. 8(1), pages 1-5, December.
    6. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    7. Anshul Kundaje & Wouter Meuleman & Jason Ernst & Misha Bilenky & Angela Yen & Alireza Heravi-Moussavi & Pouya Kheradpour & Zhizhuo Zhang & Jianrong Wang & Michael J. Ziller & Viren Amin & John W. Whit, 2015. "Integrative analysis of 111 reference human epigenomes," Nature, Nature, vol. 518(7539), pages 317-330, February.
    8. Andrew V. Anzalone & Peyton B. Randolph & Jessie R. Davis & Alexander A. Sousa & Luke W. Koblan & Jonathan M. Levy & Peter J. Chen & Christopher Wilson & Gregory A. Newby & Aditya Raguram & David R. L, 2019. "Search-and-replace genome editing without double-strand breaks or donor DNA," Nature, Nature, vol. 576(7785), pages 149-157, December.
    9. Alexis C. Komor & Yongjoo B. Kim & Michael S. Packer & John A. Zuris & David R. Liu, 2016. "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage," Nature, Nature, vol. 533(7603), pages 420-424, May.
    10. Gregory M. Findlay & Riza M. Daza & Beth Martin & Melissa D. Zhang & Anh P. Leith & Molly Gasperini & Joseph D. Janizek & Xingfan Huang & Lea M. Starita & Jay Shendure, 2018. "Accurate classification of BRCA1 variants with saturation genome editing," Nature, Nature, vol. 562(7726), pages 217-222, October.
    11. Sarah Djebali & Carrie A. Davis & Angelika Merkel & Alex Dobin & Timo Lassmann & Ali Mortazavi & Andrea Tanzer & Julien Lagarde & Wei Lin & Felix Schlesinger & Chenghai Xue & Georgi K. Marinov & Jaina, 2012. "Landscape of transcription in human cells," Nature, Nature, vol. 489(7414), pages 101-108, September.
    12. Nicole M. Gaudelli & Alexis C. Komor & Holly A. Rees & Michael S. Packer & Ahmed H. Badran & David I. Bryson & David R. Liu, 2017. "Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage," Nature, Nature, vol. 551(7681), pages 464-471, November.
    13. Wei He & Liang Zhang & Oscar D. Villarreal & Rongjie Fu & Ella Bedford & Jingzhuang Dou & Anish Y. Patel & Mark T. Bedford & Xiaobing Shi & Taiping Chen & Blaine Bartholomew & Han Xu, 2019. "De novo identification of essential protein domains from CRISPR-Cas9 tiling-sgRNA knockout screens," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

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