Aganezov, S., Goodwin, S., Sherman, R. M., Sedlazeck, F. J., Arun, G., Bhatia, S., Lee, I., Kirsche, M., Wappel, R., Kramer, M., Kostroff, K., Spector, D. L., Timp, W., McCombie, W. R., Schatz, M. C.
(September 2020)
Comprehensive analysis of structural variants in breast cancer genomes using single-molecule sequencing.
Genome Res, 30 (9).
pp. 1258-1273.
ISSN 1088-9051 (Print)1088-9051
Abstract
Improved identification of structural variants (SVs) in cancer can lead to more targeted and effective treatment options as well as advance our basic understanding of the disease and its progression. We performed whole-genome sequencing of the SKBR3 breast cancer cell line and patient-derived tumor and normal organoids from two breast cancer patients using Illumina/10x Genomics, Pacific Biosciences (PacBio), and Oxford Nanopore Technologies (ONT) sequencing. We then inferred SVs and large-scale allele-specific copy number variants (CNVs) using an ensemble of methods. Our findings show that long-read sequencing allows for substantially more accurate and sensitive SV detection, with between 90% and 95% of variants supported by each long-read technology also supported by the other. We also report high accuracy for long reads even at relatively low coverage (25×-30×). Furthermore, we integrated SV and CNV data into a unifying karyotype-graph structure to present a more accurate representation of the mutated cancer genomes. We find hundreds of variants within known cancer-related genes detectable only through long-read sequencing. These findings highlight the need for long-read sequencing of cancer genomes for the precise analysis of their genetic instability.
| Item Type: |
Paper
|
| Additional Information: |
1549-5469
Aganezov, Sergey
Goodwin, Sara
Sherman, Rachel M
Sedlazeck, Fritz J
Orcid: 0000-0001-6040-2691
Arun, Gayatri
Bhatia, Sonam
Lee, Isac
Kirsche, Melanie
Wappel, Robert
Kramer, Melissa
Kostroff, Karen
Spector, David L
Timp, Winston
Orcid: 0000-0003-2083-6027
McCombie, W Richard
Schatz, Michael C
P30 CA045508/CA/NCI NIH HHS/United States
R01 HG006677/HG/NHGRI NIH HHS/United States
R01 HG009190/HG/NHGRI NIH HHS/United States
R21 CA220411/CA/NCI NIH HHS/United States
Journal Article
Genome Res. 2020 Sep;30(9):1258-1273. doi: 10.1101/gr.260497.119. Epub 2020 Sep 4. |
| Subjects: |
bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
diseases & disorders > neoplasms
Investigative techniques and equipment > assays
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organs, tissues, organelles, cell types and functions
Investigative techniques and equipment > assays > RNA-seq
structural biology |
| CSHL Authors: |
|
| Communities: |
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL labs > McCombie lab
CSHL labs > Schatz lab
CSHL labs > Spector lab
CSHL Cancer Center Program
CSHL Cancer Center Shared Resources > Sequencing Technology & Analysis Service |
| Depositing User: |
Matthew Dunn
|
| Date: |
September 2020 |
| Date Deposited: |
20 Apr 2021 02:27 |
| Last Modified: |
13 Feb 2024 19:46 |
| PMCID: |
PMC7545150 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/39842 |
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