Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution

Abstract The dynamic three-dimensional spatial conformations of chromosomes demonstrate complex structural variations across single cells, which plays pivotal roles in modulating single-cell specific transcription and epigenetics landscapes. The high rates of missing contacts in single-cell chromati...

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Main Authors: Hao Wang, Jiaxin Yang, Xinrui Yu, Yu Zhang, Jianliang Qian, Jianrong Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58674-w
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author Hao Wang
Jiaxin Yang
Xinrui Yu
Yu Zhang
Jianliang Qian
Jianrong Wang
author_facet Hao Wang
Jiaxin Yang
Xinrui Yu
Yu Zhang
Jianliang Qian
Jianrong Wang
author_sort Hao Wang
collection DOAJ
description Abstract The dynamic three-dimensional spatial conformations of chromosomes demonstrate complex structural variations across single cells, which plays pivotal roles in modulating single-cell specific transcription and epigenetics landscapes. The high rates of missing contacts in single-cell chromatin contact maps impose significant challenges to reconstruct high-resolution spatial chromatin configurations. We develop a data-driven algorithm, Tensor-FLAMINGO, based on a low-rank tensor completion strategy. Implemented on a diverse panel of single-cell chromatin datasets, Tensor-FLAMINGO generates 10kb- and 30kb-resolution spatial chromosomal architectures across individual cells. Tensor-FLAMINGO achieves superior accuracy in reconstructing 3D chromatin structures, recovering missing contacts, and delineating cell clusters. The unprecedented high-resolution characterization of single-cell genome folding enables expanded identification of single-cell specific long-range chromatin interactions, multi-way spatial hubs, and the mechanisms of disease-associated GWAS variants. Beyond the sparse 2D contact maps, the complete 3D chromatin conformations promote an avenue to understand the dynamics of spatially coordinated molecular processes across different cells.
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publishDate 2025-04-01
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record_format Article
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spelling doaj-art-5e5edc0b4f744b5193b4bf934c1d66f92025-08-20T02:17:13ZengNature PortfolioNature Communications2041-17232025-04-0116112210.1038/s41467-025-58674-wTensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolutionHao Wang0Jiaxin Yang1Xinrui Yu2Yu Zhang3Jianliang Qian4Jianrong Wang5Department of Computational Mathematics, Science and Engineering, Michigan State UniversityDepartment of Computational Mathematics, Science and Engineering, Michigan State UniversityDepartment of Computational Mathematics, Science and Engineering, Michigan State UniversityDepartment of Microbiology, Genetics, and Immunology, Michigan State UniversityDepartment of Computational Mathematics, Science and Engineering, Michigan State UniversityDepartment of Computational Mathematics, Science and Engineering, Michigan State UniversityAbstract The dynamic three-dimensional spatial conformations of chromosomes demonstrate complex structural variations across single cells, which plays pivotal roles in modulating single-cell specific transcription and epigenetics landscapes. The high rates of missing contacts in single-cell chromatin contact maps impose significant challenges to reconstruct high-resolution spatial chromatin configurations. We develop a data-driven algorithm, Tensor-FLAMINGO, based on a low-rank tensor completion strategy. Implemented on a diverse panel of single-cell chromatin datasets, Tensor-FLAMINGO generates 10kb- and 30kb-resolution spatial chromosomal architectures across individual cells. Tensor-FLAMINGO achieves superior accuracy in reconstructing 3D chromatin structures, recovering missing contacts, and delineating cell clusters. The unprecedented high-resolution characterization of single-cell genome folding enables expanded identification of single-cell specific long-range chromatin interactions, multi-way spatial hubs, and the mechanisms of disease-associated GWAS variants. Beyond the sparse 2D contact maps, the complete 3D chromatin conformations promote an avenue to understand the dynamics of spatially coordinated molecular processes across different cells.https://doi.org/10.1038/s41467-025-58674-w
spellingShingle Hao Wang
Jiaxin Yang
Xinrui Yu
Yu Zhang
Jianliang Qian
Jianrong Wang
Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
Nature Communications
title Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
title_full Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
title_fullStr Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
title_full_unstemmed Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
title_short Tensor-FLAMINGO unravels the complexity of single-cell spatial architectures of genomes at high-resolution
title_sort tensor flamingo unravels the complexity of single cell spatial architectures of genomes at high resolution
url https://doi.org/10.1038/s41467-025-58674-w
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