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Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation
BACKGROUND: The assessment of cell-free circulating DNA fragments, also known as a "liquid biopsy" of the patient's plasma, is an important source for the discovery and subsequent non-invasive monitoring of cancer and other pathological conditions. Although the nucleosome-guided fragm...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686799/ https://www.ncbi.nlm.nih.gov/pubmed/26693644 http://dx.doi.org/10.1186/1471-2164-16-S13-S1 |
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author | Ivanov, Maxim Baranova, Ancha Butler, Timothy Spellman, Paul Mileyko, Vladislav |
author_facet | Ivanov, Maxim Baranova, Ancha Butler, Timothy Spellman, Paul Mileyko, Vladislav |
author_sort | Ivanov, Maxim |
collection | PubMed |
description | BACKGROUND: The assessment of cell-free circulating DNA fragments, also known as a "liquid biopsy" of the patient's plasma, is an important source for the discovery and subsequent non-invasive monitoring of cancer and other pathological conditions. Although the nucleosome-guided fragmentation patterns of cell-free DNA (cfDNA) have not yet been studied in detail, non-random representation of cfDNA sequencies may reflect chromatin features in the tissue of origin at gene-regulation level. RESULTS: In this study, we investigated the association between epigenetic landscapes of human tissues evident in the patterns of cfDNA in plasma by deep sequencing of human cfDNA samples. We have demonstrated that baseline characteristics of cfDNA fragmentation pattern are in concordance with the ones corresponding to cell lines-derived. To identify the loci differentially represented in cfDNA fragment, we mapped the transcription start sites within the sequenced cfDNA fragments and tested for association of these genomic coordinates with the relative strength and the patterns of gene expressions. Preselected sets of house-keeping and tissue specific genes were used as models for actively expressed and silenced genes. Developed measure of gene regulation was able to differentiate these two sets based on sequencing coverage near gene transcription start site. CONCLUSION: Experimental outcomes suggest that cfDNA retains characteristics previously noted in genome-wide analysis of chromatin structure, in particular, in MNase-seq assays. Thus far the analysis of the DNA fragmentation pattern may aid further developing of cfDNA based biomarkers for a variety of human conditions. |
format | Online Article Text |
id | pubmed-4686799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46867992015-12-31 Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation Ivanov, Maxim Baranova, Ancha Butler, Timothy Spellman, Paul Mileyko, Vladislav BMC Genomics Research BACKGROUND: The assessment of cell-free circulating DNA fragments, also known as a "liquid biopsy" of the patient's plasma, is an important source for the discovery and subsequent non-invasive monitoring of cancer and other pathological conditions. Although the nucleosome-guided fragmentation patterns of cell-free DNA (cfDNA) have not yet been studied in detail, non-random representation of cfDNA sequencies may reflect chromatin features in the tissue of origin at gene-regulation level. RESULTS: In this study, we investigated the association between epigenetic landscapes of human tissues evident in the patterns of cfDNA in plasma by deep sequencing of human cfDNA samples. We have demonstrated that baseline characteristics of cfDNA fragmentation pattern are in concordance with the ones corresponding to cell lines-derived. To identify the loci differentially represented in cfDNA fragment, we mapped the transcription start sites within the sequenced cfDNA fragments and tested for association of these genomic coordinates with the relative strength and the patterns of gene expressions. Preselected sets of house-keeping and tissue specific genes were used as models for actively expressed and silenced genes. Developed measure of gene regulation was able to differentiate these two sets based on sequencing coverage near gene transcription start site. CONCLUSION: Experimental outcomes suggest that cfDNA retains characteristics previously noted in genome-wide analysis of chromatin structure, in particular, in MNase-seq assays. Thus far the analysis of the DNA fragmentation pattern may aid further developing of cfDNA based biomarkers for a variety of human conditions. BioMed Central 2015-12-16 /pmc/articles/PMC4686799/ /pubmed/26693644 http://dx.doi.org/10.1186/1471-2164-16-S13-S1 Text en Copyright © 2015 Ivanov et al. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ivanov, Maxim Baranova, Ancha Butler, Timothy Spellman, Paul Mileyko, Vladislav Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title | Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title_full | Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title_fullStr | Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title_full_unstemmed | Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title_short | Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation |
title_sort | non-random fragmentation patterns in circulating cell-free dna reflect epigenetic regulation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686799/ https://www.ncbi.nlm.nih.gov/pubmed/26693644 http://dx.doi.org/10.1186/1471-2164-16-S13-S1 |
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