Inferring cellular communication through mapping cells in space using Tangram 2

Huang, H.; Andersson, A.; Wu, S. Z.; Scalia, G.; Hoi, K. H.; Collier, J.; Heimberg, G.; Corrada Bravo, H.; Gaddam, S.; Huetter, J.-C.; Muller, S.; Turley, S.; Richmond, D. L.; Bentaieb, A.; Biancalani, T.

doi:10.1101/2025.09.28.679077

bioRxiv · 10.1101/2025.09.28.679077

Inferring cellular communication through mapping cells in space using Tangram 2

Huang, H.·Andersson, A.·Wu, S. Z.·Scalia, G.·Hoi, K. H.·Collier, J.·Heimberg, G.·Corrada Bravo, H.·Gaddam, S.·Huetter, J.-C.·Muller, S.·Turley, S.·Richmond, D. L.·Bentaieb, A.·Biancalani, T.

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Abstract

Cell-to-cell communication (CCC) shapes development, immunity, and disease, yet current spatial transcriptomics (SRT) platforms rarely achieve both single-cell resolution and high-quality transcriptome-wide coverage to accurately characterize CCC in the tissue microenvironment. Tangram2 bridges this gap by integrating single-cell RNA sequencing (scRNA-seq) with SRT to identify genes whose expression changes as a function of neighboring cell types. By accurately mapping cells in tissue space, Tangram2 disentangles interaction-driven transcriptional shifts from intrinsic identity markers, yielding mechanistic CCC maps. Validation across diverse settings--including Slide-tags, co-cultured experiments, human lymph nodes, and simulations--demonstrates high accuracy. Applied to triple-negative breast cancer (TNBC) and cutaneous squamous cell carcinoma (cSCC), Tangram2 recapitulates known biology and uncovers new hypotheses, including various immunosuppressive mechanisms in TNBC and a macrophage-regulatory T-cell circuit associated with survival in cSCC.

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Huang, H., Andersson, A., Wu, S. Z., Scalia, G., Hoi, K. H., Collier, J., Heimberg, G., Corrada Bravo, H., Gaddam, S., Huetter, J.-C., Muller, S., Turley, S., Richmond, D. L., Bentaieb, A., Biancalani, T.. 2025-09-30. Inferring cellular communication through mapping cells in space using Tangram 2. https://doi.org/10.1101/2025.09.28.679077

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