Simultaneous sequencing of genetic and epigenetic bases in DNA
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Published:2023-02-06
Issue:10
Volume:41
Page:1457-1464
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ISSN:1087-0156
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Container-title:Nature Biotechnology
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language:en
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Short-container-title:Nat Biotechnol
Author:
Füllgrabe Jens, Gosal Walraj S., Creed Páidí, Liu Sidong, Lumby Casper K.ORCID, Morley David J., Ost Tobias W. B., Vilella Albert J.ORCID, Yu Shirong, Bignell Helen, Burns Philippa, Charlesworth Tom, Fu Beiyuan, Fordham Howerd, Harding Nicolas J., Gandelman Olga, Golder Paula, Hodson Christopher, Li Mengjie, Lila Marjana, Liu Yang, Mason Joanne, Mellad Jason, Monahan Jack M.ORCID, Nentwich Oliver, Palmer Alexandra, Steward Michael, Taipale Minna, Vandomme Audrey, San-Bento Rita Santo, Singhal Ankita, Vivian JuliaORCID, Wójtowicz Natalia, Williams Nathan, Walker Nicolas J.ORCID, Wong Nicola C. H., Yalloway Gary N., Holbrook Joanna D.ORCID, Balasubramanian ShankarORCID
Abstract
AbstractDNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine.
Publisher
Springer Science and Business Media LLC
Subject
Biomedical Engineering,Molecular Medicine,Applied Microbiology and Biotechnology,Bioengineering,Biotechnology
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