Performance differences in spatial transcriptomics platforms identify Treg biology in human inflammatory bowel disease [Xenium]

ABSTRACT: Spatial transcriptomics is a rapidly growing field with the potential to enhance our ability to uncover novel biology, support drug development, and guide biomarker discovery. However, a biologically validated comparison of leading single-cell-level spatial transcriptomics platforms to guide scientists is lacking in the field. Using intestinal biopsies (n = 40) from patients with inflammatory bowel disease (IBD) of varying disease states and disease locations and non-diseased controls, we systematically compared two imaging based spatial transcriptomics platforms (CosMx and Xenium) to guide translational work for two NIDDK supported IBD consortiums and the Crohn’s and Colitis Foundation Plexus Biorepository. In vitro experiments were conducted to validate key biologic findings. We present a comprehensive data resource of over 1.5 million spatially profiled intestinal cells from healthy and IBD samples. We observed CosMx to have overall better data quality than Xenium in both ulcerative colitis and Crohn’s disease across the full spectrum of commercially available panels. The performance of Xenium, but not CosMx, was significantly influenced by block quality and panel size, with a decline in data quality as the panel size increased. We demonstrate operational feasibility for CosMx in multi-center studies, and CosMx uniquely identified Treg-associated biology in both ulcerative colitis and Crohn’s disease which was validated by in vitro experiments. This study highlights the performance differences between CosMx and Xenium, demonstrating the strengths of CosMx for biology discovery in IBD research. Further studies are needed to explore the broader applicability of CosMx in other gastrointestinal conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE312420 | GEO | 2026/03/13

REPOSITORIES: GEO