Author:
Baslan Timour,Kendall Jude,Ward Brian,Cox Hilary,Leotta Anthony,Rodgers Linda,Riggs Michael,D'Italia Sean,Sun Guoli,Yong Mao,Miskimen Kristy,Gilmore Hannah,Saborowski Michael,Dimitrova Nevenka,Krasnitz Alexander,Harris Lyndsay,Wigler Michael,Hicks James
Abstract
Genome-wide analysis at the level of single cells has recently emerged as a powerful tool to dissect genome heterogeneity in cancer, neurobiology, and development. To be truly transformative, single-cell approaches must affordably accommodate large numbers of single cells. This is feasible in the case of copy number variation (CNV), because CNV determination requires only sparse sequence coverage. We have used a combination of bioinformatic and molecular approaches to optimize single-cell DNA amplification and library preparation for highly multiplexed sequencing, yielding a method that can produce genome-wide CNV profiles of up to a hundred individual cells on a single lane of an Illumina HiSeq instrument. We apply the method to human cancer cell lines and biopsied cancer tissue, thereby illustrating its efficiency, reproducibility, and power to reveal underlying genetic heterogeneity and clonal phylogeny. The capacity of the method to facilitate the rapid profiling of hundreds to thousands of single-cell genomes represents a key step in making single-cell profiling an easily accessible tool for studying cell lineage.
Funder
National Cancer Institute Cancer Center Shared
Department of the Army
Breast Cancer Research Fund
American Cancer Society
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
112 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献