Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Chongwei Bi; Lin Wang; Baolei Yuan; Xuan Zhou; Yu Li; sheng wang; Yuhong Pang; Xin Gao; Yanyi Huang; Mo Li

doi:10.1186/s13059-020-02143-8

Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Chongwei Bi, Lin Wang, Baolei Yuan, Xuan Zhou, Yu Li, sheng wang, Yuhong Pang, Xin Gao, Yanyi Huang, Mo Li

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5 , using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in singlenucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.

Original language	English (US)
Journal	Genome biology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s13059-020-02143-8
State	Published - Aug 24 2020

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10.1186/s13059-020-02143-8

https://repository.kaust.edu.sa/bitstream/10754/661565/4/Long%20Read.pdf

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Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
Bi, C. (Creator), Wang, L. (Creator), Yuan, B. (Creator), Zhou, X. (Creator), Li, Y. (Creator), Wang, S. (Creator), Pang, Y. (Creator), Gao, X. (Creator), Huang, Y. (Creator), Li, M. (Creator), Wang, L. (Creator), Pang, Y. (Creator) & Huang, Y. (Creator), figshare, 2020
DOI: 10.6084/m9.figshare.c.5100908, http://hdl.handle.net/10754/664976
Dataset
Individual-molecule Sequencing (IDMseq) of PANX1 gene in hESCs
Bi, C. (Creator), Wang, L. (Creator), Yuan, B. (Creator), Zhou, X. (Creator), Huang, Y. (Creator), Li, M. (Creator), Li, Y. (Creator), Pang, Y. (Creator), Gao, X. (Creator), wang, S. (Creator), Wang, L. (Creator), Huang, Y. (Creator), Pang, Y. (Creator), wang, S. (Creator), Wang, L. (Creator), zhou, X. (Creator), Huang, Y. (Creator), Pang, Y. (Creator) & wang, S. (Creator), NCBI, Feb 12 2020
http://hdl.handle.net/10754/666916
Dataset

Cite this

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title = "Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs",

abstract = "Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5 , using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in singlenucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.",

author = "Chongwei Bi and Lin Wang and Baolei Yuan and Xuan Zhou and Yu Li and sheng wang and Yuhong Pang and Xin Gao and Yanyi Huang and Mo Li",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): URF/1/3412-01-01), BAS/1/1080-01",

year = "2020",

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doi = "10.1186/s13059-020-02143-8",

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T1 - Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

AU - Bi, Chongwei

AU - Wang, Lin

AU - Yuan, Baolei

AU - Zhou, Xuan

AU - Li, Yu

AU - wang, sheng

AU - Pang, Yuhong

AU - Gao, Xin

AU - Huang, Yanyi

AU - Li, Mo

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): URF/1/3412-01-01), BAS/1/1080-01

PY - 2020/8/24

Y1 - 2020/8/24

N2 - Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5 , using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in singlenucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.

AB - Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5 , using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in singlenucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.

UR - http://hdl.handle.net/10754/661565

UR - https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-02143-8

U2 - 10.1186/s13059-020-02143-8

DO - 10.1186/s13059-020-02143-8

M3 - Article

C2 - 32831134

VL - 21

JO - Genome Biology

JF - Genome Biology

SN - 1465-6914

IS - 1

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Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Abstract

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Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Individual-molecule Sequencing (IDMseq) of PANX1 gene in hESCs

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