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

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...

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Main Authors: Chongwei Bi, Lin Wang, Baolei Yuan, Xuan Zhou, Yu Li, Sheng Wang, Yuhong Pang, Xin Gao, Yanyi Huang, Mo Li
Format: Article
Language:English
Published: BMC 2020-08-01
Series:Genome Biology
Subjects:
Human embryonic stem cell
CRISPR-Cas9
Genome editing
Nanopore sequencing
Long-read sequencing
Next-generation sequencing
Online Access:http://link.springer.com/article/10.1186/s13059-020-02143-8
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spelling doaj-8ac7efe6f33542c18c341407186c7d782020-11-25T03:30:18ZengBMCGenome Biology1474-760X2020-08-0121111410.1186/s13059-020-02143-8Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCsChongwei Bi0Lin Wang1Baolei Yuan2Xuan Zhou3Yu Li4Sheng Wang5Yuhong Pang6Xin Gao7Yanyi Huang8Mo Li9Laboratory of Stem Cell and Regeneration, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Laboratory of Stem Cell and Regeneration, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Laboratory of Stem Cell and Regeneration, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Laboratory of Stem Cell and Regeneration, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST)Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST)Beijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry, College of Engineering, Peking-Tsinghua Center for Life Sciences, Peking UniversityComputational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST)Beijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry, College of Engineering, Peking-Tsinghua Center for Life Sciences, Peking UniversityLaboratory of Stem Cell and Regeneration, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)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 single-nucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.http://link.springer.com/article/10.1186/s13059-020-02143-8Human embryonic stem cellCRISPR-Cas9Genome editingNanopore sequencingLong-read sequencingNext-generation sequencing
collection DOAJ
language English
format Article
sources DOAJ
author Chongwei Bi
Lin Wang
Baolei Yuan
Xuan Zhou
Yu Li
Sheng Wang
Yuhong Pang
Xin Gao
Yanyi Huang
Mo Li
spellingShingle Chongwei Bi
Lin Wang
Baolei Yuan
Xuan Zhou
Yu Li
Sheng Wang
Yuhong Pang
Xin Gao
Yanyi Huang
Mo Li
Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
Genome Biology
Human embryonic stem cell
CRISPR-Cas9
Genome editing
Nanopore sequencing
Long-read sequencing
Next-generation sequencing
author_facet Chongwei Bi
Lin Wang
Baolei Yuan
Xuan Zhou
Yu Li
Sheng Wang
Yuhong Pang
Xin Gao
Yanyi Huang
Mo Li
author_sort Chongwei Bi
title Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_short Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_full Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_fullStr Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_full_unstemmed Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_sort long-read individual-molecule sequencing reveals crispr-induced genetic heterogeneity in human escs
publisher BMC
series Genome Biology
issn 1474-760X
publishDate 2020-08-01
description 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 single-nucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.
topic Human embryonic stem cell
CRISPR-Cas9
Genome editing
Nanopore sequencing
Long-read sequencing
Next-generation sequencing
url http://link.springer.com/article/10.1186/s13059-020-02143-8
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