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Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct

The three-dimensional structure of chromatin in the cellular nucleus carries important information that is connected to physiological and pathological correlates and dysfunctional cell behaviour. As direct observation is not feasible at present, on one side, several experimental techniques have been...

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Autores principales: Caudai, Claudia, Zoppè, Monica, Tonazzini, Anna, Merelli, Ivan, Salerno, Emanuele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072831/
https://www.ncbi.nlm.nih.gov/pubmed/33923796
http://dx.doi.org/10.3390/biology10040338
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author Caudai, Claudia
Zoppè, Monica
Tonazzini, Anna
Merelli, Ivan
Salerno, Emanuele
author_facet Caudai, Claudia
Zoppè, Monica
Tonazzini, Anna
Merelli, Ivan
Salerno, Emanuele
author_sort Caudai, Claudia
collection PubMed
description The three-dimensional structure of chromatin in the cellular nucleus carries important information that is connected to physiological and pathological correlates and dysfunctional cell behaviour. As direct observation is not feasible at present, on one side, several experimental techniques have been developed to provide information on the spatial organization of the DNA in the cell; on the other side, several computational methods have been developed to elaborate experimental data and infer 3D chromatin conformations. The most relevant experimental methods are Chromosome Conformation Capture and its derivatives, chromatin immunoprecipitation and sequencing techniques (CHIP-seq), RNA-seq, fluorescence in situ hybridization (FISH) and other genetic and biochemical techniques. All of them provide important and complementary information that relate to the three-dimensional organization of chromatin. However, these techniques employ very different experimental protocols and provide information that is not easily integrated, due to different contexts and different resolutions. Here, we present an open-source tool, which is an expansion of the previously reported code ChromStruct, for inferring the 3D structure of chromatin that, by exploiting a multilevel approach, allows an easy integration of information derived from different experimental protocols and referred to different resolution levels of the structure, from a few kilobases up to Megabases. Our results show that the introduction of chromatin modelling features related to CTCF CHIA-PET data, histone modification CHIP-seq, and RNA-seq data produce appreciable improvements in ChromStruct’s 3D reconstructions, compared to the use of HI-C data alone, at a local level and at a very high resolution.
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spelling pubmed-80728312021-04-27 Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct Caudai, Claudia Zoppè, Monica Tonazzini, Anna Merelli, Ivan Salerno, Emanuele Biology (Basel) Article The three-dimensional structure of chromatin in the cellular nucleus carries important information that is connected to physiological and pathological correlates and dysfunctional cell behaviour. As direct observation is not feasible at present, on one side, several experimental techniques have been developed to provide information on the spatial organization of the DNA in the cell; on the other side, several computational methods have been developed to elaborate experimental data and infer 3D chromatin conformations. The most relevant experimental methods are Chromosome Conformation Capture and its derivatives, chromatin immunoprecipitation and sequencing techniques (CHIP-seq), RNA-seq, fluorescence in situ hybridization (FISH) and other genetic and biochemical techniques. All of them provide important and complementary information that relate to the three-dimensional organization of chromatin. However, these techniques employ very different experimental protocols and provide information that is not easily integrated, due to different contexts and different resolutions. Here, we present an open-source tool, which is an expansion of the previously reported code ChromStruct, for inferring the 3D structure of chromatin that, by exploiting a multilevel approach, allows an easy integration of information derived from different experimental protocols and referred to different resolution levels of the structure, from a few kilobases up to Megabases. Our results show that the introduction of chromatin modelling features related to CTCF CHIA-PET data, histone modification CHIP-seq, and RNA-seq data produce appreciable improvements in ChromStruct’s 3D reconstructions, compared to the use of HI-C data alone, at a local level and at a very high resolution. MDPI 2021-04-16 /pmc/articles/PMC8072831/ /pubmed/33923796 http://dx.doi.org/10.3390/biology10040338 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caudai, Claudia
Zoppè, Monica
Tonazzini, Anna
Merelli, Ivan
Salerno, Emanuele
Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title_full Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title_fullStr Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title_full_unstemmed Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title_short Integration of Multiple Resolution Data in 3D Chromatin Reconstruction Using ChromStruct
title_sort integration of multiple resolution data in 3d chromatin reconstruction using chromstruct
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072831/
https://www.ncbi.nlm.nih.gov/pubmed/33923796
http://dx.doi.org/10.3390/biology10040338
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