High resolution copy number inference in cancer using short-molecule nanopore sequencing.

Baslan, Timour, Kovaka, Sam, Sedlazeck, Fritz J, Zhang, Yanming, Wappel, Robert, Tian, Sha, Lowe, Scott W, Goodwin, Sara, Schatz, Michael C (September 2021) High resolution copy number inference in cancer using short-molecule nanopore sequencing. Nucleic Acids Research. ISSN 0305-1048

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Abstract

Genome copy number is an important source of genetic variation in health and disease. In cancer, Copy Number Alterations (CNAs) can be inferred from short-read sequencing data, enabling genomics-based precision oncology. Emerging Nanopore sequencing technologies offer the potential for broader clinical utility, for example in smaller hospitals, due to lower instrument cost, higher portability, and ease of use. Nonetheless, Nanopore sequencing devices are limited in the number of retrievable sequencing reads/molecules compared to short-read sequencing platforms, limiting CNA inference accuracy. To address this limitation, we targeted the sequencing of short-length DNA molecules loaded at optimized concentration in an effort to increase sequence read/molecule yield from a single nanopore run. We show that short-molecule nanopore sequencing reproducibly returns high read counts and allows high quality CNA inference. We demonstrate the clinical relevance of this approach by accurately inferring CNAs in acute myeloid leukemia samples. The data shows that, compared to traditional approaches such as chromosome analysis/cytogenetics, short molecule nanopore sequencing returns more sensitive, accurate copy number information in a cost effective and expeditious manner, including for multiplex samples. Our results provide a framework for short-molecule nanopore sequencing with applications in research and medicine, which includes but is not limited to, CNAs.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer 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 diseases & disorders > neoplasms diseases & disorders > cancer > cancer types > acute myeloid leukemia 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 > computational biology bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types
CSHL Authors:	Baslan, Timour Wappel, Robert Lowe, Scott W. Goodwin, Sara Schatz, Michael C.
Communities:	CSHL labs > Krasnitz lab CSHL labs > Lowe lab CSHL labs > McCombie lab CSHL labs > Schatz lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	22 September 2021
Date Deposited:	30 Sep 2021 18:05
Last Modified:	09 Feb 2024 21:05
PMCID:	PMC8643650
URI:	https://repository.cshl.edu/id/eprint/40375

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