Refinement strategies for Tangram for reliable single-cell to spatial mapping

Stahl M, Straßer LJ, Lio CT, Bernett J, Röttger R, List M (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Bioinformatics (Oxford, England) Oxford University Press (OUP): Policy B - Oxford Open Option B

Book Volume: 41

Pages Range: i552-i560

DOI: 10.1093/bioinformatics/btaf194

Abstract

Motivation Single-cell RNA sequencing (scRNA-seq) provides comprehensive gene expression data at a single-cell level but lacks spatial context. In contrast, spatial transcriptomics captures both spatial and transcriptional information but is limited by resolution, sensitivity, or feasibility. No single technology combines both the high spatial resolution and deep transcriptomic profiling at the single-cell level without tradeoffs. Spatial mapping tools that integrate scRNA-seq and spatial transcriptomics data are crucial to bridge this gap. However, we found that Tangram, one of the most prominent spatial mapping tools, provides inconsistent results over repeated runs. Results We refine Tangram to achieve more consistent cell mappings and investigate the challenges that arise from data characteristics. We find that the mapping quality depends on the gene expression sparsity. To address this, we (1) train the model on an informative gene subset, (2) apply cell filtering, (3) introduce several forms of regularization, and (4) incorporate neighborhood information. Evaluations on real and simulated mouse datasets demonstrate that this approach improves both gene expression prediction and cell mapping. Consistent cell mapping strengthens the reliability of the projection of cell annotations and features into space, gene imputation, and correction of low-quality measurements. Our pipeline, which includes gene set and hyperparameter selection, can serve as guidance for applying Tangram on other datasets, while our benchmarking framework with data simulation and inconsistency metrics is useful for evaluating other tools or Tangram modifications.

Authors with CRIS profile

Judith Bernett

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) University of Southern Denmark / Syddansk Universitet DK Denmark (DK)

How to cite

APA:

Stahl, M., Straßer, L.J., Lio, C.T., Bernett, J., Röttger, R., & List, M. (2025). Refinement strategies for Tangram for reliable single-cell to spatial mapping. Bioinformatics (Oxford, England), 41, i552-i560. https://doi.org/10.1093/bioinformatics/btaf194

MLA:

Stahl, Merle, et al. "Refinement strategies for Tangram for reliable single-cell to spatial mapping." Bioinformatics (Oxford, England) 41 (2025): i552-i560.

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