3D-Guided Scalable Flow Matching for Generating Volumetric Tissue Spatial Transcriptomics from Serial Histology

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Auteurs principaux: Sanian, Mohammad Vali, Hemmat, Arshia, Vahidi, Amirhossein, Maaskola, Jonas, Lee, Jimmy Tsz Hang, Makarchuk, Stanislaw, Demirci, Yeliz, Chipampe, Nana-Jane, Haniffa, Muzlifah, Bayraktar, Omer, Paavolainen, Lassi, Lotfollahi, Mohammad
Format: Preprint
Publié: 2025
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author Sanian, Mohammad Vali
Hemmat, Arshia
Vahidi, Amirhossein
Maaskola, Jonas
Lee, Jimmy Tsz Hang
Makarchuk, Stanislaw
Demirci, Yeliz
Chipampe, Nana-Jane
Haniffa, Muzlifah
Bayraktar, Omer
Paavolainen, Lassi
Lotfollahi, Mohammad
author_facet Sanian, Mohammad Vali
Hemmat, Arshia
Vahidi, Amirhossein
Maaskola, Jonas
Lee, Jimmy Tsz Hang
Makarchuk, Stanislaw
Demirci, Yeliz
Chipampe, Nana-Jane
Haniffa, Muzlifah
Bayraktar, Omer
Paavolainen, Lassi
Lotfollahi, Mohammad
contents A scalable and robust 3D tissue transcriptomics profile can enable a holistic understanding of tissue organization and provide deeper insights into human biology and disease. Most predictive algorithms that infer ST directly from histology treat each section independently and ignore 3D structure, while existing 3D-aware approaches are not generative and do not scale well. We present Holographic Tissue Expression Inpainting and Analysis (HoloTea), a 3D-aware flow-matching framework that imputes spot-level gene expression from H&E while explicitly using information from adjacent sections. Our key idea is to retrieve morphologically corresponding spots on neighboring slides in a shared feature space and fuse this cross section context into a lightweight ControlNet, allowing conditioning to follow anatomical continuity. To better capture the count nature of the data, we introduce a 3D-consistent prior for flow matching that combines a learned zero-inflated negative binomial (ZINB) prior with a spatial-empirical prior constructed from neighboring sections. A global attention block introduces 3D H&E scaling linearly with the number of spots in the slide, enabling training and inference on large 3D ST datasets. Across three spatial transcriptomics datasets spanning different tissue types and resolutions, HoloTea consistently improves 3D expression accuracy and generalization compared to 2D and 3D baselines. We envision HoloTea advancing the creation of accurate 3D virtual tissues, ultimately accelerating biomarker discovery and deepening our understanding of disease.
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id arxiv_https___arxiv_org_abs_2511_14613
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle 3D-Guided Scalable Flow Matching for Generating Volumetric Tissue Spatial Transcriptomics from Serial Histology
Sanian, Mohammad Vali
Hemmat, Arshia
Vahidi, Amirhossein
Maaskola, Jonas
Lee, Jimmy Tsz Hang
Makarchuk, Stanislaw
Demirci, Yeliz
Chipampe, Nana-Jane
Haniffa, Muzlifah
Bayraktar, Omer
Paavolainen, Lassi
Lotfollahi, Mohammad
Computer Vision and Pattern Recognition
A scalable and robust 3D tissue transcriptomics profile can enable a holistic understanding of tissue organization and provide deeper insights into human biology and disease. Most predictive algorithms that infer ST directly from histology treat each section independently and ignore 3D structure, while existing 3D-aware approaches are not generative and do not scale well. We present Holographic Tissue Expression Inpainting and Analysis (HoloTea), a 3D-aware flow-matching framework that imputes spot-level gene expression from H&E while explicitly using information from adjacent sections. Our key idea is to retrieve morphologically corresponding spots on neighboring slides in a shared feature space and fuse this cross section context into a lightweight ControlNet, allowing conditioning to follow anatomical continuity. To better capture the count nature of the data, we introduce a 3D-consistent prior for flow matching that combines a learned zero-inflated negative binomial (ZINB) prior with a spatial-empirical prior constructed from neighboring sections. A global attention block introduces 3D H&E scaling linearly with the number of spots in the slide, enabling training and inference on large 3D ST datasets. Across three spatial transcriptomics datasets spanning different tissue types and resolutions, HoloTea consistently improves 3D expression accuracy and generalization compared to 2D and 3D baselines. We envision HoloTea advancing the creation of accurate 3D virtual tissues, ultimately accelerating biomarker discovery and deepening our understanding of disease.
title 3D-Guided Scalable Flow Matching for Generating Volumetric Tissue Spatial Transcriptomics from Serial Histology
topic Computer Vision and Pattern Recognition
url https://arxiv.org/abs/2511.14613