Comparison of Capture Hi-C Analytical Pipelines

<div><p>It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e...

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Main Author: Dina Aljogol (12011672) (author)
Other Authors: I. Richard Thompson (4278694) (author), Cameron S. Osborne (7244990) (author), Borbala Mifsud (3907267) (author)
Published: 2022
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author Dina Aljogol (12011672)
author2 I. Richard Thompson (4278694)
Cameron S. Osborne (7244990)
Borbala Mifsud (3907267)
author2_role author
author
author
author_facet Dina Aljogol (12011672)
I. Richard Thompson (4278694)
Cameron S. Osborne (7244990)
Borbala Mifsud (3907267)
author_role author
dc.creator.none.fl_str_mv Dina Aljogol (12011672)
I. Richard Thompson (4278694)
Cameron S. Osborne (7244990)
Borbala Mifsud (3907267)
dc.date.none.fl_str_mv 2022-01-28T03:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fgene.2022.786501
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Comparison_of_Capture_Hi-C_Analytical_Pipelines/25532968
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
epigenetics
gene regulation
computational pipeline
capture Hi-C
chromatin organization
dc.title.none.fl_str_mv Comparison of Capture Hi-C Analytical Pipelines
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e.g., 3C and its successors 4C, 5C and Hi-C), which is accompanied by the development of computational pipelines to identify biologically meaningful chromatin contacts in such data. However, not all tools are applicable to all experimental designs and all structural features. Capture Hi-C (CHi-C) is a method that uses an intermediate hybridization step to target and select predefined regions of interest in a Hi-C library, thereby increasing effective sequencing depth for those regions. It allows researchers to investigate fine chromatin structures at high resolution, for instance promoter-enhancer loops, but it introduces additional biases with the capture step, and therefore requires specialized pipelines. Here, we compare multiple analytical pipelines for CHi-C data analysis. We consider the effect of retaining multi-mapping reads and compare the efficiency of different statistical approaches in both identifying reproducible interactions and determining biologically significant interactions. At restriction fragment level resolution, the number of multi-mapping reads that could be rescued was negligible. The number of identified interactions varied widely, depending on the analytical method, indicating large differences in type I and type II error rates. The optimal pipeline depends on the project-specific tolerance level of false positive and false negative chromatin contacts.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Genetics<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2022.786501" target="_blank">https://dx.doi.org/10.3389/fgene.2022.786501</a></p>
eu_rights_str_mv openAccess
id Manara2_31d3ea3d8cee49f48bbc265f53763002
identifier_str_mv 10.3389/fgene.2022.786501
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25532968
publishDate 2022
repository.mail.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Comparison of Capture Hi-C Analytical PipelinesDina Aljogol (12011672)I. Richard Thompson (4278694)Cameron S. Osborne (7244990)Borbala Mifsud (3907267)Biological sciencesGeneticsepigeneticsgene regulationcomputational pipelinecapture Hi-Cchromatin organization<div><p>It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e.g., 3C and its successors 4C, 5C and Hi-C), which is accompanied by the development of computational pipelines to identify biologically meaningful chromatin contacts in such data. However, not all tools are applicable to all experimental designs and all structural features. Capture Hi-C (CHi-C) is a method that uses an intermediate hybridization step to target and select predefined regions of interest in a Hi-C library, thereby increasing effective sequencing depth for those regions. It allows researchers to investigate fine chromatin structures at high resolution, for instance promoter-enhancer loops, but it introduces additional biases with the capture step, and therefore requires specialized pipelines. Here, we compare multiple analytical pipelines for CHi-C data analysis. We consider the effect of retaining multi-mapping reads and compare the efficiency of different statistical approaches in both identifying reproducible interactions and determining biologically significant interactions. At restriction fragment level resolution, the number of multi-mapping reads that could be rescued was negligible. The number of identified interactions varied widely, depending on the analytical method, indicating large differences in type I and type II error rates. The optimal pipeline depends on the project-specific tolerance level of false positive and false negative chromatin contacts.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Genetics<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2022.786501" target="_blank">https://dx.doi.org/10.3389/fgene.2022.786501</a></p>2022-01-28T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fgene.2022.786501https://figshare.com/articles/journal_contribution/Comparison_of_Capture_Hi-C_Analytical_Pipelines/25532968CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255329682022-01-28T03:00:00Z
spellingShingle Comparison of Capture Hi-C Analytical Pipelines
Dina Aljogol (12011672)
Biological sciences
Genetics
epigenetics
gene regulation
computational pipeline
capture Hi-C
chromatin organization
status_str publishedVersion
title Comparison of Capture Hi-C Analytical Pipelines
title_full Comparison of Capture Hi-C Analytical Pipelines
title_fullStr Comparison of Capture Hi-C Analytical Pipelines
title_full_unstemmed Comparison of Capture Hi-C Analytical Pipelines
title_short Comparison of Capture Hi-C Analytical Pipelines
title_sort Comparison of Capture Hi-C Analytical Pipelines
topic Biological sciences
Genetics
epigenetics
gene regulation
computational pipeline
capture Hi-C
chromatin organization