ArticleNature methods2025
Resolving tissue complexity by multimodal spatial omics modeling with MISO.
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Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
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64citing papers in PubMed
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Who cites it
64 citing papers in PubMed.
- 3D multi-omics tumour atlases: from technology to biology and clinical translation.Nature reviews. Cancer · 2026Review
- The dual-enhanced graph learning framework DePass allows paired data integration in single-cell and spatial multiomics.Nature cell biology · 2026Article
- Semi-metric optimal transport enables robust spatial multi-omics integration.Research square · 2026Article
- SpaMOAL is a deep learning method that enables accurate spatial domain identification from multi-omics data.PLoS biology · 2026Article
- HESTIA: scalable multimodal integration of histology and high-resolution spatial Transcriptomics for robust spatial domain identification.Briefings in bioinformatics · 2026Article
- Continual integration of single-cell multimodal data with MIRACLE.Nature computational science · 2026Article
- Unified representation learning for spatial multi-omics.Bioinformatics (Oxford, England) · 2026Article
- scENature communications · 2026Article
- Integrated Spatial and Bulk Untargeted Metabolomics Characterize Location- and Histology-Associated Metabolic Heterogeneity in Colorectal Cancer.Journal of proteome research · 2026Article
- Image-guided spatial omics enhancement reveals hidden spatial microstructures.Bioinformatics (Oxford, England) · 2026Article
- Integrating pathological morphologies and molecular profiles for clinical biomarker discovery with unified multimodal embedding.Clinical and translational medicine · 2026Article
- Decoding Spatial Heterogeneity and Multi-Omics Regulation with Hierarchical Graph Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial multi-omics imputation and embedding with SpaMIE.Cell reports methods · 2026Article
- NicheProt: Cell-type-resolved proteomics of tissue compartments.Science advances · 2026Article
- Multimodal spatial omics: From data acquisition to computational integration.Patterns (New York, N.Y.) · 2026Review
- LYNX: a deep generative model for linking spatial dynamics and cell interactions in multimodal spatial data.bioRxiv : the preprint server for biology · 2026Article
- Histopathology-centered computational evolution of spatial omics: integration, mapping, and foundation models.Briefings in bioinformatics · 2026Review
- Computational analysis in spatial transcriptomics: methods and perspectives.Briefings in bioinformatics · 2026Review
- ARISE: RNA-anchored shared-edge topology and hierarchical fusion for spatial multi-omics integration.Bioinformatics (Oxford, England) · 2026Article
- SpaMFG: a spatial multi-omics integration method based on feature grouping.Bioinformatics (Oxford, England) · 2026Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
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Authors and funding
28 authors.
Kyle ColemanDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. kyle.coleman@cshs.org.ORCID http://orcid.org/0000-0002-9726-2335
Amelia SchroederStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Melanie LothStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Daiwei ZhangStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jeong Hwan ParkDepartment of Pathology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.ORCID http://orcid.org/0000-0003-4522-9928
Ji-Youn SungDepartment of Pathology, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
Niklas BlankDepartment of Microbiology, Institute for Immunology, and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexis J CowanDepartment of Microbiology, Institute for Immunology, and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Xuyu QianDivision of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jianfeng ChenDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jiahui JiangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hanying YanStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9227-1742
Laith Z SamarahDepartment of Chemistry, Lewis Sigler Institute for Integrative Genomics, and Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Jean R ClemenceauDepartment of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Inyeop JangDepartment of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Minji KimDepartment of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Isabel BarnfatherDepartment of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0009-0007-3071-963X
Joshua D RabinowitzDepartment of Chemistry, Lewis Sigler Institute for Integrative Genomics, and Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-1247-4727
Yanxiang DengDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9975-8086
Edward B LeeDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4589-1180
Alexander LazarDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6395-4499
Jianjun GaoDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Emma E FurthDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tae Hyun HwangDepartment of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Linghua WangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9380-0266
Christoph A ThaissDepartment of Microbiology, Institute for Immunology, and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8226-7718
Jian HuDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA. jian.hu@emory.edu.ORCID http://orcid.org/0000-0003-2852-7675
Mingyao LiStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mingyao@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-8180-0621
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MClinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MVIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3MThe Penn Human Precision Pain Center (HPPC): Discovery and Functional Evaluation of Human Primary Somatosensory Neuron Types at Normal and Chronic Pain ConditionsU19NS135528 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Mingyao Li, Wenqin Luo · 2023 to 2026
$11.2MCenter for Gastric Pre-Cancer Atlas of Multidimensional Evolution in 3D (GAME3D)U01CA294518 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Paul F Mansfield, Linghua Wang · 2024 to 2026
$5.4MPASSCODE (Pancreatic Adenocarcinoma Stromal Reprograming ConSortium COordination, Data Management and Education)U24CA274274 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI J. Jack LEE, ANIRBAN MAITRA · 2022 to 2026
$4.9MTumor cell lineage diversity and composition in gastric cancer progression and therapy resistanceR01CA266280 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Pawel K. Mazur, Linghua Wang · 2022 to 2026
$3.2MEffective combination therapy for MTAP-deficient bladder carcinoma by targeting metabolic vulnerability and modulating tumor immune microenvironmentR01CA254988 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAO, JIANJUN · 2021 to 2025
$2.6MSingle-Cell Transcriptomic Analysis of Human RetinaR01EY030192 · NEI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO · 2019 to 2022
$2.6MDecoding tumor metabolic and immunologic interactions driving racial disparity in African American patients with bladder cancer.R01CA282282 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Jianjun Gao, Nagireddy Putluri · 2023 to 2026
$2.5MIntegrative analysis of spatial transcriptomics with histology images and single cellsR01HG013185 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Mingyao Li · 2023 to 2026
$2.2MSpatial and temporal tumor-immune co-evolution and interactions that model lung adenocarcinoma developmentU01CA264583 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Humam Kadara, Linghua Wang · 2022 to 2026
$2.1MNCATS NIH HHS UL1 TR001873NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA190578NCI NIH HHS R01 CA254988NCI NIH HHS R01 CA266280NCI NIH HHS R01 CA269489NCI NIH HHS R01 CA276690NCI NIH HHS R01 CA282282NCI NIH HHS U01 CA264583NCI NIH HHS U01 CA294518NCI NIH HHS U24 CA274274NEI NIH HHS R01 EY030192NHGRI NIH HHS R01 HG013185NHLBI NIH HHS R01 HL171595NIDDK NIH HHS P30 DK019525NINDS NIH HHS K99 NS135123NINDS NIH HHS U19 NS135528NLM NIH HHS R01 LM014592U.S. Department of Defense (United States Department of Defense) CA190578U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01EY030192U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL171595U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01LM014592U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01CA294518U.S. Department of Health & Human Services | National Institutes of Health (NIH) U19NS135582U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) K99NS135123U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01CA254988U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01CA266280U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01CA269489U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01CA276690U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01CA282282U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) U01CA264583U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) U24CA274274
Abstract
Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets. MISO (MultI-modal Spatial Omics) is a versatile algorithm for feature extraction and clustering, capable of integrating multiple modalities from diverse spatial omics experiments with high spatial resolution. Its effectiveness is demonstrated across various datasets, encompassing gene expression, protein expression, epigenetics, metabolomics and tissue histology modalities. MISO outperforms existing methods in identifying biologically relevant spatial domains, representing a substantial advancement in multimodal spatial omics analysis. Moreover, MISO's computational efficiency ensures its scalability to handle large-scale datasets generated by subcellular resolution spatial omics technologies.
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