Fig. 4

A rectal gene signature is associated with response to UC induction therapy and microbial shifts. Samples loading PC1 (Z score) values of the corticosteroid response gene signature are shown for controls and the discovery cohort of 152 moderate-severe UC patients stratified by a WK4 clinical remission (R) and b mucosal healing (fecal calprotectin < 250 mcg/gm). Samples loading PC1 values derived from an independent 3′UTR Lexogen mRNASeq platform are shown for the discovery cohort and an independent validation cohort stratified by c WK4 clinical remission (R), or by d mucosal healing as in (b) for the validation cohort. Samples loading PC1 values including controls and e the GSE16879²⁰ data set of UC treated with anti-TNF and f GSE73661²³ of UC treated with anti-integrin α₄β₇. R: mucosal healing defined by colonoscopy. g Functional annotation enrichment analyses of the corticosteroid response gene signature and the top 50 genes that were differentially expressed in pretreatment colon biopsies of anti-TNF refractory vs. responsive UC patients²¹. The full list of enriched functions and P values are in Supplementary Dataset 4. Genes are in blue and biologic functions in pink; connections to each signature are as shown. h Heat map summarizing Spearman similarity measures between microbial abundances and gene expression using hierarchical all-against-all association. *False discovery rate < 0.2. Blue and red indicate negative and positive associations, respectively. i Graphical summary of the cohort and main findings. Box and whisker plot with central line indicating median, box ends representing upper and lower quartile, and whisker represent 10–90 percentile. Mann−Whitney and ANOVA FDR as applicable, *P < 0.05, **P < 0.01, ***P < 0.001, ****<0.0001