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Targeted bisulfite sequencing of the dynamic DNA methylome
BACKGROUND: The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome at single-nucleotide resolutio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135789/ https://www.ncbi.nlm.nih.gov/pubmed/27980681 http://dx.doi.org/10.1186/s13072-016-0105-1 |
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author | Ziller, Michael J. Stamenova, Elena K. Gu, Hongcang Gnirke, Andreas Meissner, Alexander |
author_facet | Ziller, Michael J. Stamenova, Elena K. Gu, Hongcang Gnirke, Andreas Meissner, Alexander |
author_sort | Ziller, Michael J. |
collection | PubMed |
description | BACKGROUND: The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome at single-nucleotide resolution, but it has a number of significant practical drawbacks that become amplified with increasing sample numbers. All other technologies capture only a fraction of the cytosines that show dynamic regulation across cell and tissue types. RESULTS: Here, we present a novel hybrid selection design focusing on loci with dynamic methylation that captures a large number of differentially methylated gene-regulatory elements. We benchmarked this assay against matched whole genome data and profiled 25 human tissue samples to explore its ability to detect differentially methylated regions. CONCLUSIONS: Our target capture design fills a major gap left by all other assays that exist to map DNA methylation. It maintains the ability to link cytosine methylation to genetic differences, the single-base resolution and the analysis of neighboring cytosines while notably reducing the cost per sample by focusing the sequencing effort on the most informative and relevant regions of the genome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0105-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5135789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51357892016-12-15 Targeted bisulfite sequencing of the dynamic DNA methylome Ziller, Michael J. Stamenova, Elena K. Gu, Hongcang Gnirke, Andreas Meissner, Alexander Epigenetics Chromatin Methodology BACKGROUND: The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome at single-nucleotide resolution, but it has a number of significant practical drawbacks that become amplified with increasing sample numbers. All other technologies capture only a fraction of the cytosines that show dynamic regulation across cell and tissue types. RESULTS: Here, we present a novel hybrid selection design focusing on loci with dynamic methylation that captures a large number of differentially methylated gene-regulatory elements. We benchmarked this assay against matched whole genome data and profiled 25 human tissue samples to explore its ability to detect differentially methylated regions. CONCLUSIONS: Our target capture design fills a major gap left by all other assays that exist to map DNA methylation. It maintains the ability to link cytosine methylation to genetic differences, the single-base resolution and the analysis of neighboring cytosines while notably reducing the cost per sample by focusing the sequencing effort on the most informative and relevant regions of the genome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0105-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-12-03 /pmc/articles/PMC5135789/ /pubmed/27980681 http://dx.doi.org/10.1186/s13072-016-0105-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 | Methodology Ziller, Michael J. Stamenova, Elena K. Gu, Hongcang Gnirke, Andreas Meissner, Alexander Targeted bisulfite sequencing of the dynamic DNA methylome |
title | Targeted bisulfite sequencing of the dynamic DNA methylome |
title_full | Targeted bisulfite sequencing of the dynamic DNA methylome |
title_fullStr | Targeted bisulfite sequencing of the dynamic DNA methylome |
title_full_unstemmed | Targeted bisulfite sequencing of the dynamic DNA methylome |
title_short | Targeted bisulfite sequencing of the dynamic DNA methylome |
title_sort | targeted bisulfite sequencing of the dynamic dna methylome |
topic | Methodology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135789/ https://www.ncbi.nlm.nih.gov/pubmed/27980681 http://dx.doi.org/10.1186/s13072-016-0105-1 |
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