Format

Send to

Choose Destination
Nat Biotechnol. 2019 Sep;37(9):1034-1037. doi: 10.1038/s41587-019-0203-2. Epub 2019 Jul 29.

Large dataset enables prediction of repair after CRISPR-Cas9 editing in primary T cells.

Leenay RT1, Aghazadeh A2, Hiatt J3,4,5,6,7, Tse D2, Roth TL4, Apathy R4, Shifrut E4, Hultquist JF7,8,9,10, Krogan N7,8,9, Wu Z11, Cirolia G1, Canaj H1, Leonetti MD1, Marson A12,13,14,15,16,17, May AP18,19, Zou J20,21,22.

Author information

1
Chan-Zuckerberg Biohub, San Francisco, CA, USA.
2
Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
3
Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
4
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
5
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
6
Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA.
7
J. David Gladstone Institutes, San Francisco, CA, USA.
8
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
9
Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA, USA.
10
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
11
Department of Chemistry, Stanford University, Stanford, CA, USA.
12
Chan-Zuckerberg Biohub, San Francisco, CA, USA. alexander.marson@ucsf.edu.
13
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
14
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
15
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. alexander.marson@ucsf.edu.
16
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
17
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. alexander.marson@ucsf.edu.
18
Chan-Zuckerberg Biohub, San Francisco, CA, USA. apmay1@gmail.com.
19
Sana Biotechnology, South San Francisco, CA, USA. apmay1@gmail.com.
20
Chan-Zuckerberg Biohub, San Francisco, CA, USA. jamesz@stanford.edu.
21
Department of Electrical Engineering, Stanford University, Stanford, CA, USA. jamesz@stanford.edu.
22
Department of Biomedical Data Science, Stanford University, Stanford, CA, USA. jamesz@stanford.edu.

Abstract

Understanding of repair outcomes after Cas9-induced DNA cleavage is still limited, especially in primary human cells. We sequence repair outcomes at 1,656 on-target genomic sites in primary human T cells and use these data to train a machine learning model, which we have called CRISPR Repair Outcome (SPROUT). SPROUT accurately predicts the length, probability and sequence of nucleotide insertions and deletions, and will facilitate design of SpCas9 guide RNAs in therapeutically important primary human cells.

PMID:
31359007
DOI:
10.1038/s41587-019-0203-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center