Identification of Crohn’s disease subtypes in single cell RNA sequencing signatures of treatment naïve samples across the paediatric gastrointestinal tract

Background Crohn’s disease (CD) is characterized by chronic intestinal inflammation. Previous single-cell transcriptomic studies have mostly focused on established disease, leaving a knowledge gap in relation to treatment-naive profiles across multiple regions of the gut. Methods To study disease onset, a treatment naïve pediatric CD cohort was recruited, and single-cell transcriptomics was performed on ileum, colon, and rectum biopsies collected at initial endoscopy. A clustering stability assessment workflow was developed to ensure clustering and downstream results were robust. Results Inflammation did not strongly influence cellular proportion due to heterogeneity across donor and tissue. Tensor decomposition revealed distinct mesenchymal and myeloid cell-mediated sources of disease pathology, corresponding to previously identified fibrotic and pro-inflammatory disease progression. Integrating transcriptomics and genome wide association summary statistics for CD suggested myeloid and T cells drive disease, highlighting potential cellular therapeutic targets. Conclusion Tensor decomposition stratified donors into clinically meaningful groups based on their transcriptomic profile, suggesting these signatures can be utilized for personalized medicine.