INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation

Abstract Recent advances in spatial epigenomic techniques have given rise to spatial assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of epigenomic heterogeneity and spatial information simultaneously. Integrative analysis of multiple spATA...

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Main Authors: Yuyao Liu, Zhen Li, Xiaoyang Chen, Xuejian Cui, Zijing Gao, Rui Jiang
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56535-0
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author Yuyao Liu
Zhen Li
Xiaoyang Chen
Xuejian Cui
Zijing Gao
Rui Jiang
author_facet Yuyao Liu
Zhen Li
Xiaoyang Chen
Xuejian Cui
Zijing Gao
Rui Jiang
author_sort Yuyao Liu
collection DOAJ
description Abstract Recent advances in spatial epigenomic techniques have given rise to spatial assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of epigenomic heterogeneity and spatial information simultaneously. Integrative analysis of multiple spATAC-seq samples, for which no method has been developed, allows for effective identification and elimination of unwanted non-biological factors within the data, enabling comprehensive exploration of tissue structures and providing a holistic epigenomic landscape, thereby facilitating the discovery of biological implications and the study of regulatory processes. In this article, we present INSTINCT, a method for multi-sample INtegration of Spatial chromaTIN accessibility sequencing data via stochastiC domain Translation. INSTINCT can efficiently handle the high dimensionality of spATAC-seq data and eliminate the complex noise and batch effects of samples through a stochastic domain translation procedure. We demonstrate the superiority and robustness of INSTINCT in integrating spATAC-seq data across multiple simulated scenarios and real datasets. Additionally, we highlight the advantages of INSTINCT in spatial domain identification, visualization, spot-type annotation, and various downstream analyses, including motif enrichment analysis, expression enrichment analysis, and partitioned heritability analysis.
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issn 2041-1723
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publisher Nature Portfolio
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spelling doaj-art-46f76b4f0eb2415087157d1f7c46bd9c2025-02-02T12:31:39ZengNature PortfolioNature Communications2041-17232025-02-0116112310.1038/s41467-025-56535-0INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translationYuyao Liu0Zhen Li1Xiaoyang Chen2Xuejian Cui3Zijing Gao4Rui Jiang5Ministry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityMinistry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityMinistry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityMinistry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityMinistry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityMinistry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua UniversityAbstract Recent advances in spatial epigenomic techniques have given rise to spatial assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of epigenomic heterogeneity and spatial information simultaneously. Integrative analysis of multiple spATAC-seq samples, for which no method has been developed, allows for effective identification and elimination of unwanted non-biological factors within the data, enabling comprehensive exploration of tissue structures and providing a holistic epigenomic landscape, thereby facilitating the discovery of biological implications and the study of regulatory processes. In this article, we present INSTINCT, a method for multi-sample INtegration of Spatial chromaTIN accessibility sequencing data via stochastiC domain Translation. INSTINCT can efficiently handle the high dimensionality of spATAC-seq data and eliminate the complex noise and batch effects of samples through a stochastic domain translation procedure. We demonstrate the superiority and robustness of INSTINCT in integrating spATAC-seq data across multiple simulated scenarios and real datasets. Additionally, we highlight the advantages of INSTINCT in spatial domain identification, visualization, spot-type annotation, and various downstream analyses, including motif enrichment analysis, expression enrichment analysis, and partitioned heritability analysis.https://doi.org/10.1038/s41467-025-56535-0
spellingShingle Yuyao Liu
Zhen Li
Xiaoyang Chen
Xuejian Cui
Zijing Gao
Rui Jiang
INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
Nature Communications
title INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
title_full INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
title_fullStr INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
title_full_unstemmed INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
title_short INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
title_sort instinct multi sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation
url https://doi.org/10.1038/s41467-025-56535-0
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