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Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy

Dying tumor cells shed DNA fragments into the circulation that are known as circulating tumor DNA (ctDNA). Liquid biopsy tests aim to detect cancer using known markers, including genetic alterations and epigenetic profiles of ctDNA. Despite various advantages, the major limitation remains the low fr...

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Autores principales: Taklifi, Pegah, Palizban, Fahimeh, Mehrmohamadi, Mahya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213477/
https://www.ncbi.nlm.nih.gov/pubmed/35729208
http://dx.doi.org/10.1038/s41598-022-14675-z
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author Taklifi, Pegah
Palizban, Fahimeh
Mehrmohamadi, Mahya
author_facet Taklifi, Pegah
Palizban, Fahimeh
Mehrmohamadi, Mahya
author_sort Taklifi, Pegah
collection PubMed
description Dying tumor cells shed DNA fragments into the circulation that are known as circulating tumor DNA (ctDNA). Liquid biopsy tests aim to detect cancer using known markers, including genetic alterations and epigenetic profiles of ctDNA. Despite various advantages, the major limitation remains the low fraction of tumor-originating DNA fragments in a high background of normal blood-cell originating fragments in the cell-free DNA (cfDNA) pool in plasma. Deep targeted sequencing of cfDNA allows for enrichment of fragments in known cancer marker-associated regions of the genome, thus increasing the chances of detecting the low fraction variant harboring fragments. Most targeted sequencing panels are designed to include known recurrent mutations or methylation markers of cancer. Here, we propose the integration of cancer-specific chromatin accessibility states into panel designs for liquid biopsy. Using machine learning approaches, we first identify accessible and inaccessible chromatin regions specific to each major human cancer type. We then introduce a score that quantifies local chromatin accessibility in tumor relative to blood cells and show that this metric can be useful for prioritizing marker regions with higher chances of being detected in cfDNA for inclusion in future panel designs.
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spelling pubmed-92134772022-06-23 Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy Taklifi, Pegah Palizban, Fahimeh Mehrmohamadi, Mahya Sci Rep Article Dying tumor cells shed DNA fragments into the circulation that are known as circulating tumor DNA (ctDNA). Liquid biopsy tests aim to detect cancer using known markers, including genetic alterations and epigenetic profiles of ctDNA. Despite various advantages, the major limitation remains the low fraction of tumor-originating DNA fragments in a high background of normal blood-cell originating fragments in the cell-free DNA (cfDNA) pool in plasma. Deep targeted sequencing of cfDNA allows for enrichment of fragments in known cancer marker-associated regions of the genome, thus increasing the chances of detecting the low fraction variant harboring fragments. Most targeted sequencing panels are designed to include known recurrent mutations or methylation markers of cancer. Here, we propose the integration of cancer-specific chromatin accessibility states into panel designs for liquid biopsy. Using machine learning approaches, we first identify accessible and inaccessible chromatin regions specific to each major human cancer type. We then introduce a score that quantifies local chromatin accessibility in tumor relative to blood cells and show that this metric can be useful for prioritizing marker regions with higher chances of being detected in cfDNA for inclusion in future panel designs. Nature Publishing Group UK 2022-06-21 /pmc/articles/PMC9213477/ /pubmed/35729208 http://dx.doi.org/10.1038/s41598-022-14675-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Taklifi, Pegah
Palizban, Fahimeh
Mehrmohamadi, Mahya
Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title_full Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title_fullStr Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title_full_unstemmed Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title_short Integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
title_sort integrating chromatin accessibility states in the design of targeted sequencing panels for liquid biopsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213477/
https://www.ncbi.nlm.nih.gov/pubmed/35729208
http://dx.doi.org/10.1038/s41598-022-14675-z
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