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Analysis of the structural variability of topologically associated domains as revealed by Hi-C
Three-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associated domains (TADs), building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824515/ https://www.ncbi.nlm.nih.gov/pubmed/31687663 http://dx.doi.org/10.1093/nargab/lqz008 |
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author | Sauerwald, Natalie Singhal, Akshat Kingsford, Carl |
author_facet | Sauerwald, Natalie Singhal, Akshat Kingsford, Carl |
author_sort | Sauerwald, Natalie |
collection | PubMed |
description | Three-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associated domains (TADs), building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region than outside the region. A central question is the degree to which TADs are conserved or vary between conditions. We analyze 137 Hi-C samples from 9 studies under 3 measures to quantify the effects of various sources of biological and experimental variation. We observe significant variation in TAD sets between both non-replicate and replicate samples, and provide initial evidence that this variability does not come from genetic sequence differences. The effects of experimental protocol differences are also measured, demonstrating that samples can have protocol-specific structural changes, but that TADs are generally robust to lab-specific differences. This study represents a systematic quantification of key factors influencing comparisons of chromosome structure, suggesting significant variability and the potential for cell-type-specific structural features, which has previously not been systematically explored. The lack of observed influence of heredity and genetic differences on chromosome structure suggests that factors other than the genetic sequence are driving this structure, which plays an important role in human disease and cellular functioning. |
format | Online Article Text |
id | pubmed-6824515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68245152019-11-06 Analysis of the structural variability of topologically associated domains as revealed by Hi-C Sauerwald, Natalie Singhal, Akshat Kingsford, Carl NAR Genom Bioinform Standard Article Three-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associated domains (TADs), building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region than outside the region. A central question is the degree to which TADs are conserved or vary between conditions. We analyze 137 Hi-C samples from 9 studies under 3 measures to quantify the effects of various sources of biological and experimental variation. We observe significant variation in TAD sets between both non-replicate and replicate samples, and provide initial evidence that this variability does not come from genetic sequence differences. The effects of experimental protocol differences are also measured, demonstrating that samples can have protocol-specific structural changes, but that TADs are generally robust to lab-specific differences. This study represents a systematic quantification of key factors influencing comparisons of chromosome structure, suggesting significant variability and the potential for cell-type-specific structural features, which has previously not been systematically explored. The lack of observed influence of heredity and genetic differences on chromosome structure suggests that factors other than the genetic sequence are driving this structure, which plays an important role in human disease and cellular functioning. Oxford University Press 2019-09-30 /pmc/articles/PMC6824515/ /pubmed/31687663 http://dx.doi.org/10.1093/nargab/lqz008 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Standard Article Sauerwald, Natalie Singhal, Akshat Kingsford, Carl Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title | Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title_full | Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title_fullStr | Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title_full_unstemmed | Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title_short | Analysis of the structural variability of topologically associated domains as revealed by Hi-C |
title_sort | analysis of the structural variability of topologically associated domains as revealed by hi-c |
topic | Standard Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824515/ https://www.ncbi.nlm.nih.gov/pubmed/31687663 http://dx.doi.org/10.1093/nargab/lqz008 |
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