IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34320-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34320-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34320-7?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
    ---><---

    References listed on IDEAS

    as
    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. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    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)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zeyu Lu & Lingtian Zhang & Qing Mu & Junyang Liu & Yu Chen & Haoyuan Wang & Yanjun Zhang & Rui Su & Ruijun Wang & Zhiying Wang & Qi Lv & Zhihong Liu & Jiasen Liu & Yunhua Li & Yanhong Zhao, 2024. "Progress in Research and Prospects for Application of Precision Gene-Editing Technology Based on CRISPR–Cas9 in the Genetic Improvement of Sheep and Goats," Agriculture, MDPI, vol. 14(3), pages 1-17, March.
    2. Marion Rosello & Malo Serafini & Luca Mignani & Dario Finazzi & Carine Giovannangeli & Marina C. Mione & Jean-Paul Concordet & Filippo Del Bene, 2022. "Disease modeling by efficient genome editing using a near PAM-less base editor in vivo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Péter István Kulcsár & András Tálas & Zoltán Ligeti & Eszter Tóth & Zsófia Rakvács & Zsuzsa Bartos & Sarah Laura Krausz & Ágnes Welker & Vanessza Laura Végi & Krisztina Huszár & Ervin Welker, 2023. "A cleavage rule for selection of increased-fidelity SpCas9 variants with high efficiency and no detectable off-targets," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Jaesuk Lee & Kayeong Lim & Annie Kim & Young Geun Mok & Eugene Chung & Sung-Ik Cho & Ji Min Lee & Jin-Soo Kim, 2023. "Prime editing with genuine Cas9 nickases minimizes unwanted indels," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Jeonghun Kwon & Minyoung Kim & Seungmin Bae & Anna Jo & Youngho Kim & Jungjoon K. Lee, 2022. "TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Dominique L. Brooks & Manuel J. Carrasco & Ping Qu & William H. Peranteau & Rebecca C. Ahrens-Nicklas & Kiran Musunuru & Mohamad-Gabriel Alameh & Xiao Wang, 2023. "Rapid and definitive treatment of phenylketonuria in variant-humanized mice with corrective editing," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    7. Annabel K. Sangree & Audrey L. Griffith & Zsofia M. Szegletes & Priyanka Roy & Peter C. DeWeirdt & Mudra Hegde & Abby V. McGee & Ruth E. Hanna & John G. Doench, 2022. "Benchmarking of SpCas9 variants enables deeper base editor screens of BRCA1 and BCL2," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Maarten H. Geurts & Shashank Gandhi & Matteo G. Boretto & Ninouk Akkerman & Lucca L. M. Derks & Gijs Son & Martina Celotti & Sarina Harshuk-Shabso & Flavia Peci & Harry Begthel & Delilah Hendriks & Pa, 2023. "One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Chengdong Zhang & Yuan Yang & Tao Qi & Yuening Zhang & Linghui Hou & Jingjing Wei & Jingcheng Yang & Leming Shi & Sang-Ging Ong & Hongyan Wang & Hui Wang & Bo Yu & Yongming Wang, 2023. "Prediction of base editor off-targets by deep learning," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Chao Yang & Zhenzhen Ma & Keshan Wang & Xingxiao Dong & Meiyu Huang & Yaqiu Li & Xiagu Zhu & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "HMGN1 enhances CRISPR-directed dual-function A-to-G and C-to-G base editing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    11. Lin Zhao & Sabrina R. T. Koseki & Rachel A. Silverstein & Nadia Amrani & Christina Peng & Christian Kramme & Natasha Savic & Martin Pacesa & Tomás C. Rodríguez & Teodora Stan & Emma Tysinger & Lauren , 2023. "PAM-flexible genome editing with an engineered chimeric Cas9," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    12. Daphne Collias & Elena Vialetto & Jiaqi Yu & Khoa Co & Éva d. H. Almási & Ann-Sophie Rüttiger & Tatjana Achmedov & Till Strowig & Chase L. Beisel, 2023. "Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Fang Liang & Yu Zhang & Lin Li & Yexin Yang & Ji-Feng Fei & Yanmei Liu & Wei Qin, 2022. "SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    14. Ronghao Chen & Yu Cao & Yajing Liu & Dongdong Zhao & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    15. Zhaohui Zhong & Guanqing Liu & Zhongjie Tang & Shuyue Xiang & Liang Yang & Lan Huang & Yao He & Tingting Fan & Shishi Liu & Xuelian Zheng & Tao Zhang & Yiping Qi & Jian Huang & Yong Zhang, 2023. "Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    18. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Michael Kosicki & Felicity Allen & Frances Steward & Kärt Tomberg & Yangyang Pan & Allan Bradley, 2022. "Cas9-induced large deletions and small indels are controlled in a convergent fashion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Roberta Esposito & Andrés Lanzós & Tina Uroda & Sunandini Ramnarayanan & Isabel Büchi & Taisia Polidori & Hugo Guillen-Ramirez & Ante Mihaljevic & Bernard Mefi Merlin & Lia Mela & Eugenio Zoni & Lusin, 2023. "Tumour mutations in long noncoding RNAs enhance cell fitness," Nature Communications, Nature, vol. 14(1), pages 1-21, 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:13:y:2022:i:1:d:10.1038_s41467-022-34320-7. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.