Single-cell transcriptomic and targeted genomic profiling reveal CRTAM and PLCB1 as novel hub genes for anti-TNFa therapy response in Crohn's disease

The lack of reliable biomarkers of response to anti-TNFa biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFa biomarker discovery towards specific immune cell sub-populations using single-cell RNA-sequencing. Overall design: The single-cell RNA sequencing was performed on PBMCs samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells, and association analysis summary. Machine learning, mendelian randomization and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFa therapy response.