Mapping the 3D genome architecture

The spatial organization of the genome plays a critical role in regulating gene expression, cellular differentiation, and genome stability. This review provides an in-depth examination of the methodologies, computational tools, and frameworks developed to map the three-dimensional (3D) architecture...

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Main Authors: Ghazaleh Tavallaee, Elias Orouji
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Computational and Structural Biotechnology Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S2001037024004392
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author Ghazaleh Tavallaee
Elias Orouji
author_facet Ghazaleh Tavallaee
Elias Orouji
author_sort Ghazaleh Tavallaee
collection DOAJ
description The spatial organization of the genome plays a critical role in regulating gene expression, cellular differentiation, and genome stability. This review provides an in-depth examination of the methodologies, computational tools, and frameworks developed to map the three-dimensional (3D) architecture of the genome, focusing on both ligation-based and ligation-free techniques. We also explore the limitations of these methods, including biases introduced by restriction enzyme digestion and ligation inefficiencies, and compare them to more recent ligation-free approaches such as Genome Architecture Mapping (GAM) and Split-Pool Recognition of Interactions by Tag Extension (SPRITE). These techniques offer unique insights into higher-order chromatin structures by bypassing ligation steps, thus enabling the capture of complex multi-way interactions that are often challenging to resolve with traditional methods. Furthermore, we discuss the integration of chromatin interaction data with other genomic layers through multimodal approaches, including recent advances in single-cell technologies like sci-HiC and scSPRITE, which help unravel the heterogeneity of chromatin architecture in development and disease.
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spelling doaj-art-2ad5de6d8c464818a3bf48592dffa64f2025-08-20T02:51:11ZengElsevierComputational and Structural Biotechnology Journal2001-03702025-01-01278910110.1016/j.csbj.2024.12.018Mapping the 3D genome architectureGhazaleh Tavallaee0Elias Orouji1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, CanadaCorrespondence to: Epigenomics Lab, Princess Margaret Cancer Centre, University Health Network (UHN), 101 College St., Toronto, ON M5G 1L7, Canada.; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, CanadaThe spatial organization of the genome plays a critical role in regulating gene expression, cellular differentiation, and genome stability. This review provides an in-depth examination of the methodologies, computational tools, and frameworks developed to map the three-dimensional (3D) architecture of the genome, focusing on both ligation-based and ligation-free techniques. We also explore the limitations of these methods, including biases introduced by restriction enzyme digestion and ligation inefficiencies, and compare them to more recent ligation-free approaches such as Genome Architecture Mapping (GAM) and Split-Pool Recognition of Interactions by Tag Extension (SPRITE). These techniques offer unique insights into higher-order chromatin structures by bypassing ligation steps, thus enabling the capture of complex multi-way interactions that are often challenging to resolve with traditional methods. Furthermore, we discuss the integration of chromatin interaction data with other genomic layers through multimodal approaches, including recent advances in single-cell technologies like sci-HiC and scSPRITE, which help unravel the heterogeneity of chromatin architecture in development and disease.http://www.sciencedirect.com/science/article/pii/S20010370240043923D genome architectureChromatin conformation captureHi-CSingle-cell genomicsEpigenomicsChromatin
spellingShingle Ghazaleh Tavallaee
Elias Orouji
Mapping the 3D genome architecture
Computational and Structural Biotechnology Journal
3D genome architecture
Chromatin conformation capture
Hi-C
Single-cell genomics
Epigenomics
Chromatin
title Mapping the 3D genome architecture
title_full Mapping the 3D genome architecture
title_fullStr Mapping the 3D genome architecture
title_full_unstemmed Mapping the 3D genome architecture
title_short Mapping the 3D genome architecture
title_sort mapping the 3d genome architecture
topic 3D genome architecture
Chromatin conformation capture
Hi-C
Single-cell genomics
Epigenomics
Chromatin
url http://www.sciencedirect.com/science/article/pii/S2001037024004392
work_keys_str_mv AT ghazalehtavallaee mappingthe3dgenomearchitecture
AT eliasorouji mappingthe3dgenomearchitecture