Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA

Autor:	Jonathan C. M. Wan, Dennis Stephens, Lingqi Luo, James R. White, Caitlin M. Stewart, Benoît Rousseau, Dana W. Y. Tsui, Luis A. Diaz
Rok vydání:	2021
Předmět:	Multidisciplinary Whole Genome Sequencing Genome Human Neoplasms Mutation General Physics and Astronomy High-Throughput Nucleotide Sequencing Humans General Chemistry Cell-Free Nucleic Acids General Biochemistry Genetics and Molecular Biology
Zdroj:	Nature communications. 13(1)
ISSN:	2041-1723
Popis:	Mutational signatures accumulate in somatic cells as an admixture of endogenous and exogenous processes that occur during an individual’s lifetime. Since dividing cells release cell-free DNA (cfDNA) fragments into the circulation, we hypothesize that plasma cfDNA might reflect mutational signatures. Point mutations in plasma whole genome sequencing (WGS) are challenging to identify through conventional mutation calling due to low sequencing coverage and low mutant allele fractions. In this proof of concept study of plasma WGS at 0.3–1.5x coverage from 215 patients and 227 healthy individuals, we show that both pathological and physiological mutational signatures may be identified in plasma. By applying machine learning to mutation profiles, patients with stage I-IV cancer can be distinguished from healthy individuals with an Area Under the Curve of 0.96. Interrogating mutational processes in plasma may enable earlier cancer detection, and might enable the assessment of cancer risk and etiology.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b62f94849039acfed100e1d97a6d0091 https://pubmed.ncbi.nlm.nih.gov/35999207 Zobrazit plný text záznamu Full text from SpringerLink