ArticleCell systems2023
Uncovering the spatial landscape of molecular interactions within the tumor microenvironment through latent spaces.
Erratum issuedOpen access · greenAbstract read
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Article in Cell systems, 2023. 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 30 papers.
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30citing papers in PubMed
5.5field-weighted citation impact, top 4% of its field
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
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- Quantitative 3D histology reveals localized immune remodeling during early pancreatic cancer progression.Cell press blue · 2026Article
- Computational Modeling of Cellular Influence Delineates Functionally Relevant and Distinct Cellular Neighborhoods in Primary and Metastatic Pancreatic Ductal Adenocarcinoma.Cancer immunology research · 2026Article
- STAPLE: automating spatial transcriptomics analysis and AI interpretation.bioRxiv : the preprint server for biology · 2026Article
- FineST: contrastive learning integrates histology and spatial transcriptomics for nuclei-resolved ligand-receptor analysis.Nature communications · 2026Article
- Deep Learning Enabled 3D Multi-Omic Analysis Reveals Molecular Signatures of Heterogeneous Response to Chemotherapy in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2026Article
- A lipid metabolism-based gene signature defines diagnosis and molecular heterogeneity in diabetic nephropathy.Iranian journal of basic medical sciences · 2026Article
- Addressing the mean-variance relationship in spatially resolved transcriptomics data with spoon.Biostatistics (Oxford, England) · 2025Article
- Whole-heart 3D reconstruction of mouse CVB3 myocarditis reveals spatial and transcriptomic heterogeneity of immune foci.Cardiovascular research · 2025Article
- A novel paradigm for single-cell annotation in stem cell research.Stem cell reports · 2025Review
- Integrative analysis of genomic and transcriptomic data informs precancer progression in the pancreas.bioRxiv : the preprint server for biology · 2025Article
- Neoadjuvant Immunotherapy Promotes the Formation of Mature Tertiary Lymphoid Structures in a Remodeled Pancreatic Tumor Microenvironment.Cancer immunology research · 2025Article
- Multiomic identification of senescent stem cell populations critical for osteoarthritis progression and therapy in subchondral bones.Science advances · 2025Article
- Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies.Medical oncology (Northwood, London, England) · 2025Review
- STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics.Advances in neural information processing systems · 2024Article
- Addressing the mean-variance relationship in spatially resolved transcriptomics data withbioRxiv : the preprint server for biology · 2024Article
- A phenotypic drug discovery approach by latent interaction in deep learning.Royal Society open science · 2024Article
- The MCIB Model: A Novel Theory for Describing the Spatial Heterogeneity of the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Image stitching algorithm for super-resolution localization microscopy combined with fluorescence noise prior.Biomedical optics express · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
30 authors at 3 institutions in 1 country.
Atul DeshpandeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Melanie LothDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dimitrios N SidiropoulosDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Shuming ZhangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Long YuanBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alexander T F BellDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qingfeng ZhuDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Won Jin HoDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cesar Santa-MariaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniele M GilkesDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stephen R Williams10x Genomics, Inc., Pleasanton, CA, USA.
Cedric R Uytingco10x Genomics, Inc., Pleasanton, CA, USA.
Jennifer Chew10x Genomics, Inc., Pleasanton, CA, USA.
Andrej Hartnett10x Genomics, Inc., Pleasanton, CA, USA.
Zachary W Bent10x Genomics, Inc., Pleasanton, CA, USA.
Alexander V FavorovDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Aleksander S PopelDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mark YarchoanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ashley KiemenDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pei-Hsun WuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA.
Kohei FujikuraDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Denis WirtzDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA; Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Laura D WoodDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lei ZhengDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elizabeth M JaffeeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert A AndersConvergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ludmila DanilovaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Genevieve Stein-O'BrienDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Luciane T KagoharaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elana J FertigDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Applied Mathematics and Statistics, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA. Electronic address: ejfertig@jhmi.edu.
Johns Hopkins University · US10X Genomics (United States) · USBloomberg (United States) · US
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6MTRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2009 to 2013
$13.7MTransforming Human Pancreatic Cancer Into An Immunologic DiseaseP01CA247886 · NCI · JOHNS HOPKINS UNIVERSITY · PI WANG, HAO · 2021 to 2025
$12.7MProject 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT, MAITRA, ANIRBAN · 2019 to 2023
$11.0MTech Core 2U54CA268083 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2022 to 2026
$10.2MTumor Microenvironment Crosstalk Drives Early Lesions in Pancreatic CancerU54CA274371 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIRBAN MAITRA, Marina Pasca Di Magliano · 2022 to 2026
$9.5MPredictive experiment-based multiscale models of the tumor immune microenvironment and immunotherapy in breast cancerR01CA138264 · NCI · JOHNS HOPKINS UNIVERSITY · PI POPEL, ALEKSANDER S. · 2009 to 2023
$8.1MTargeting the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer with a Neoadjuvant Platform Clinical TrialR01CA197296 · NCI · JOHNS HOPKINS UNIVERSITY · PI William Reece Burns, Eric Christenson · 2015 to 2026
$5.7MIntegrating bioinformatics into multiscale models for hepatocellular carcinomaU01CA212007 · NCI · JOHNS HOPKINS UNIVERSITY · PI EWALD, ANDREW JOSEF, FERTIG, ELANA · 2018 to 2022
$3.2MValidation of Nuclear Morphology as a Biomarker of Aging and Aging-Related PhenotypesU01AG060903 · NIA · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2018 to 2022
$3.1MInterrogation of the Impact of Selection on the Evolution of Human PancreaticCancer Precursor LesionsU01CA271273 · NCI · JOHNS HOPKINS UNIVERSITY · PI Elana Fertig, Rachel Karchin · 2022 to 2026
$2.8MNCI NIH HHS F31 CA268724NCI NIH HHS P01 CA247886NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA062924NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA138264NCI NIH HHS R01 CA197296NCI NIH HHS R50 CA243627NCI NIH HHS U01 CA212007NCI NIH HHS U01 CA253403NCI NIH HHS U01 CA271273NCI NIH HHS U54 CA143868NCI NIH HHS U54 CA268083NCI NIH HHS U54 CA274371NIAMS NIH HHS U54 AR081774NIA NIH HHS U01 AG060903NINDS NIH HHS K99 NS122085NINDS NIH HHS R00 NS122085
Abstract
Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sample while retaining its spatial context. This technology enables unprecedented in situ resolution of the regulatory pathways that underlie the heterogeneity in the tumor as well as the tumor microenvironment (TME). The direct characterization of cellular co-localization with spatial technologies facilities quantification of the molecular changes resulting from direct cell-cell interaction, as it occurs in tumor-immune interactions. We present SpaceMarkers, a bioinformatics algorithm to infer molecular changes from cell-cell interactions from latent space analysis of ST data. We apply this approach to infer the molecular changes from tumor-immune interactions in Visium spatial transcriptomics data of metastasis, invasive and precursor lesions, and immunotherapy treatment. Further transfer learning in matched scRNA-seq data enabled further quantification of the specific cell types in which SpaceMarkers are enriched. Altogether, SpaceMarkers can identify the location and context-specific molecular interactions within the TME from ST data.
Indexed as
AlgorithmsTumor MicroenvironmentCell CommunicationComputational BiologyGene Expression Profilingcell-cell interactionslatent space factorizationsingle-cell transcriptomicsspatial analysisspatial transcriptomicstransfer learningtumor microenvironment
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