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

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

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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",

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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

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DO - 10.1186/s13059-020-02143-8

M3 - Article

C2 - 32831134

VL - 21

JO - Genome Biology

JF - Genome Biology

SN - 1465-6914

IS - 1

ER -

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

Abstract

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