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Targeted DNA methylation from cell-free DNA using hybridization probe capture

Cell-free (cf)DNA signatures are quickly becoming the target of choice for non-invasive screening, diagnosis, treatment and monitoring of human tumors. DNA methylation changes occur early in tumorigenesis and are widespread, making cfDNA methylation an attractive cancer biomarker. Already a proven t...

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Autores principales: Buckley, David N, Gooden, Gerald, Feng, Kuan, Enk, Jacob, Salhia, Bodour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803870/
https://www.ncbi.nlm.nih.gov/pubmed/36601578
http://dx.doi.org/10.1093/nargab/lqac099
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author Buckley, David N
Gooden, Gerald
Feng, Kuan
Enk, Jacob
Salhia, Bodour
author_facet Buckley, David N
Gooden, Gerald
Feng, Kuan
Enk, Jacob
Salhia, Bodour
author_sort Buckley, David N
collection PubMed
description Cell-free (cf)DNA signatures are quickly becoming the target of choice for non-invasive screening, diagnosis, treatment and monitoring of human tumors. DNA methylation changes occur early in tumorigenesis and are widespread, making cfDNA methylation an attractive cancer biomarker. Already a proven technology for targeted genome sequencing, hybridization probe capture is emerging as a method for high-throughput targeted methylation profiling suitable to liquid biopsy samples. However, to date there are no reports describing the performance of this approach in terms of reproducibility, scalability, and accuracy. In the current study we performed hybridization probe capture using the myBaits(®) Custom Methyl-seq kit on 172 plasma samples and standards to evaluate its performance on cfDNA methylation analysis. The myBaits(®) assay showed high target recovery (>90%), demonstrated excellent reproducibility between captures (R(2) = 0.92 on average), and was unaffected by increasing the number of targets in a capture. Finally, myBaits(®) accurately replicated ‘gold standard’ beta values from WGBS (average R(2) = 0.79). The results of this study show that custom targeted methylation sequencing with myBaits(®) offers a cost-effective, reliable platform to profile DNA methylation at a set of discrete custom regions, with potential applicability to liquid biopsies for cancer monitoring.
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spelling pubmed-98038702023-01-03 Targeted DNA methylation from cell-free DNA using hybridization probe capture Buckley, David N Gooden, Gerald Feng, Kuan Enk, Jacob Salhia, Bodour NAR Genom Bioinform High Throughput Sequencing Methods Cell-free (cf)DNA signatures are quickly becoming the target of choice for non-invasive screening, diagnosis, treatment and monitoring of human tumors. DNA methylation changes occur early in tumorigenesis and are widespread, making cfDNA methylation an attractive cancer biomarker. Already a proven technology for targeted genome sequencing, hybridization probe capture is emerging as a method for high-throughput targeted methylation profiling suitable to liquid biopsy samples. However, to date there are no reports describing the performance of this approach in terms of reproducibility, scalability, and accuracy. In the current study we performed hybridization probe capture using the myBaits(®) Custom Methyl-seq kit on 172 plasma samples and standards to evaluate its performance on cfDNA methylation analysis. The myBaits(®) assay showed high target recovery (>90%), demonstrated excellent reproducibility between captures (R(2) = 0.92 on average), and was unaffected by increasing the number of targets in a capture. Finally, myBaits(®) accurately replicated ‘gold standard’ beta values from WGBS (average R(2) = 0.79). The results of this study show that custom targeted methylation sequencing with myBaits(®) offers a cost-effective, reliable platform to profile DNA methylation at a set of discrete custom regions, with potential applicability to liquid biopsies for cancer monitoring. Oxford University Press 2022-12-31 /pmc/articles/PMC9803870/ /pubmed/36601578 http://dx.doi.org/10.1093/nargab/lqac099 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle High Throughput Sequencing Methods
Buckley, David N
Gooden, Gerald
Feng, Kuan
Enk, Jacob
Salhia, Bodour
Targeted DNA methylation from cell-free DNA using hybridization probe capture
title Targeted DNA methylation from cell-free DNA using hybridization probe capture
title_full Targeted DNA methylation from cell-free DNA using hybridization probe capture
title_fullStr Targeted DNA methylation from cell-free DNA using hybridization probe capture
title_full_unstemmed Targeted DNA methylation from cell-free DNA using hybridization probe capture
title_short Targeted DNA methylation from cell-free DNA using hybridization probe capture
title_sort targeted dna methylation from cell-free dna using hybridization probe capture
topic High Throughput Sequencing Methods
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803870/
https://www.ncbi.nlm.nih.gov/pubmed/36601578
http://dx.doi.org/10.1093/nargab/lqac099
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