PMCID
PMC13060804

Reconstructing biologically coherent cellular profiles from imaging-based spatial transcriptomics.

bioRxiv : the preprint server for biology
Authors
Keywords
Abstract

In imaging-based spatial transcriptomics, transcript-to-cell assignment shapes downstream biological interpretation including cell typing, ligand-receptor inference, and niche characterization. However, two-dimensional segmentation of volumetric tissue often yields mixed cellular profiles, while cells without detected nuclei are missed entirely, distorting the aforementioned downstream analyses. We present TRACER, which refines cellular representations in imaging-based transcriptomics by leveraging gene-gene coherence and spatial co-localization of transcripts observed directly in the data, without requiring external annotations or reference atlases. TRACER resolves mixed cellular profiles and reconstructs partial cells whose nuclei are not detected, enabling more complete representation of cells within the tissue section. We also introduce coherence-based metrics that quantify transcriptional purity and conflict, enabling platform-agnostic benchmarking of segmentation quality. Across diverse platforms, tissues, and segmentation methodologies, TRACER consistently and reproducibly improves the coherence of cellular profiles and the quality of downstream analyses.

Year of Publication
2026
Journal
bioRxiv : the preprint server for biology
Date Published
04/2026
ISSN
2692-8205
DOI
10.64898/2026.03.08.710395
PubMed ID
41959255
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