HiCMamba: Enhancing Hi-C resolution and identifying 3D genome structures with state space modeling

Hi-C technology measures genome-wide interaction frequencies, providing a powerful tool for studying the 3D genomic structure within the nucleus. However, high sequencing costs and technical challenges often result in Hi-C data with limited coverage, leading to imprecise estimates of chromatin interaction frequencies. To address this issue, we present a novel deep learning-based method HiCMamba to enhance the resolution of Hi-C contact maps using a state space model. We adopt the UNet-based auto-encoder architecture to stack the proposed holistic scan block, enabling the perception of both global and local receptive fields at multiple scales. Experimental results demonstrate that HiCMamba outperforms state-of-the-art methods while significantly reducing computational resources. Furthermore, the 3D genome structures, including topologically associating domains (TADs) and loops, identified in the contact maps recovered by HiCMamba are validated through associated epigenomic features. Our work demonstrates the potential of a state space model as foundational frameworks in the field of Hi-C resolution enhancement. The data and source code used in this work are available at GitHub: https://github.com/myang998/HiCMamba.

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Publication Details

Journal
PLoS Computational Biology
Published
2026-03-24
DOI
https://doi.org/10.1371/journal.pcbi.1014057
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
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article

HiCMamba: Enhancing Hi-C resolution and identifying 3D genome structures with state space modeling

PLoS Computational Biology
Genomics and Chromatin Dynamics
article

HiCMamba: Enhancing Hi-C resolution and identifying 3D genome structures with state space modeling

article en

Abstract

Hi-C technology measures genome-wide interaction frequencies, providing a powerful tool for studying the 3D genomic structure within the nucleus. However, high sequencing costs and technical challenges often result in Hi-C data with limited coverage, leading to imprecise estimates of chromatin interaction frequencies. To address this issue, we present a novel deep learning-based method HiCMamba to enhance the resolution of Hi-C contact maps using a state space model. We adopt the UNet-based auto-encoder architecture to stack the proposed holistic scan block, enabling the perception of both global and local receptive fields at multiple scales. Experimental results demonstrate that HiCMamba outperforms state-of-the-art methods while significantly reducing computational resources. Furthermore, the 3D genome structures, including topologically associating domains (TADs) and loops, identified in the contact maps recovered by HiCMamba are validated through associated epigenomic features. Our work demonstrates the potential of a state space model as foundational frameworks in the field of Hi-C resolution enhancement. The data and source code used in this work are available at GitHub: https://github.com/myang998/HiCMamba.

PLoS Computational BiologyVol. 22(3)
City University of Hong Kong (HK), Virginia Commonwealth University (US), Hong Kong University of Science and Technology (HK), City College of Dongguan University of Technology (CN), University of Hong Kong (HK), South China University of Technology (CN)
Openalex Percentile: Top 10%
Genomics and Chromatin Dynamics
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HiCMamba: Enhancing Hi-C resolution and identifying 3D genome structures with state space modeling · PLoS Computational Biology (2026) | TGRS Research Map | TGRS