Gene Ontology clustering of genes differentially expressed between HHT and control BOECs. (A) Expression of genes encoding TGF-β/BMP ligands ([i] TGF-β1, [ii] BMP6), and extracellular matrix BMP/TGF-β sequestration and activation proteins ([iii] LTBP1, [iv] FBN1, [v] LRRC32, and [vi] POSTN encoding latent TGFβ-binding protein 1, fibrillin 1, leucine-rich repeat containing 32, and periostin, respectively). Expression was DeSeq2 normalized^59,60 using low–GINI coefficient genes^61,62 that displayed least variability in BOECs (supplemental Table 2; supplemental Figure 8), although these genes were also differentially expressed when normalized only to total reads per library. Box plots show interquartile range and error bars (minimum to maximum). P values were calculated by Kruskal-Wallis test. Control (C) black, ACVRL1^+/− (A^+/−) is highlighted purple; ENG^+/− (E^+/−) blue; SMAD4^+/− (S^+/−) orange. (B) All significant terms enriched by clustering genes differentially expressed to (i) Bonferroni P < .05 (n = 30); and (ii) Bonferroni P < 1.00 (n = 161). (C) Specific terms enriched by clustering the most differentially expressed genes in each data set examining each category from top 100 to top 1500 separately. The lowest P value for each cluster is displayed. Note consistency with the most enriched terms displayed in panel B, and for further detail, see supplemental Figure 9. (D) Comparison of expression for each of the 9 “Bonferroni P < .05” genes that clustered to both isopeptide-bond and ubiquitin-like conjugation in panel B, by BOEC genotype color-coded as in panel A. Mean, standard deviation, and Kruskal-Wallis P values displayed; posttest pairwise P values by Dunn's test: ∗P < .05, ∗∗P < .01, and ∗∗∗P < .005; ns, not significant at P ≥ .05.