Integrative single-cell analysis of allele-specific copy number alterations and chromatin accessibility in canceropen access
- Authors
- Wu, Chi-Yun; Lau, Billy T.; Kim, HEON SEOK; Sathe, Anuja; Grimes, Susan M.; Ji, Hanlee P.; Zhang, Nancy R.
- Issue Date
- Oct-2021
- Publisher
- NATURE PORTFOLIO
- Citation
- NATURE BIOTECHNOLOGY, v.39, no.10, pp.1259 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE BIOTECHNOLOGY
- Volume
- 39
- Number
- 10
- Start Page
- 1259
- End Page
- +
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/190343
- DOI
- 10.1038/s41587-021-00911-w
- ISSN
- 1087-0156
- Abstract
- Cancer progression is driven by both somatic copy number aberrations (CNAs) and chromatin remodeling, yet little is known about the interplay between these two classes of events in shaping the clonal diversity of cancers. We present Alleloscope, a method for allele-specific copy number estimation that can be applied to single-cell DNA- and/or transposase-accessible chromatin-sequencing (scDNA-seq, ATAC-seq) data, enabling combined analysis of allele-specific copy number and chromatin accessibility. On scDNA-seq data from gastric, colorectal and breast cancer samples, with validation using matched linked-read sequencing, Alleloscope finds pervasive occurrence of highly complex, multiallelic CNAs, in which cells that carry varying allelic configurations adding to the same total copy number coevolve within a tumor. On scATAC-seq from two basal cell carcinoma samples and a gastric cancer cell line, Alleloscope detected multiallelic copy number events and copy-neutral loss-of-heterozygosity, enabling dissection of the contributions of chromosomal instability and chromatin remodeling to tumor evolution.,Alleloscope reveals how tumor evolution depends on allele-specific copy number changes and chromatin remodeling.,
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