Cross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections

Kaitlin M. Stouffer (), Alain Trouvé, Laurent Younes, Michael Kunst, Lydia Ng, Hongkui Zeng, Manjari Anant, Jean Fan, Yongsoo Kim, Xiaoyin Chen, Mara Rue and Michael I. Miller ()
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Kaitlin M. Stouffer: Johns Hopkins University
Alain Trouvé: ENS Paris-Saclay
Laurent Younes: Johns Hopkins University
Michael Kunst: Allen Institute for Brain Science
Lydia Ng: Allen Institute for Brain Science
Hongkui Zeng: Allen Institute for Brain Science
Manjari Anant: Johns Hopkins University
Jean Fan: Johns Hopkins University
Yongsoo Kim: Penn State University, College of Medicine
Xiaoyin Chen: Allen Institute for Brain Science
Mara Rue: Allen Institute for Brain Science
Michael I. Miller: Johns Hopkins University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction.

Date: 2024
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DOI: 10.1038/s41467-024-47883-4

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