Figure 10. Dysregulated EoE transcriptome genes in family 443.

Heatmap from RNA sequencing of patient esophageal biopsies showing log₂ fragments per kilobase of transcript per million mapped reads (FPKM) values for EoE transcriptome genes (n = 36) and significant dysregulation in family 443 individuals I.1 and II.1 during active disease (dashed rectangle) compared with unrelated patients with active eosinophilic esophagitis (EoE) and normal controls (NL) (P < 0.05, fold change > 2.0) (A). Network analysis of family 443–specific EoE transcriptome genes (red hexagons) showing significantly enriched Gene Ontology (GO) terms (B). Heatmap from RNA sequencing of esophageal epithelial cell line (EPC2) cells grown at the air-liquid interface (ALI) showing log₂ FPKM values of dysregulated genes in family 443 (from A) that are also regulated by IL-13 (+ IL-13; 100 ng/ml for 6 days) in vitro (n = 12 genes) (P < 0.05, fold change > 2.0 compared with untreated [untx] cells) (C). FPKM plot for RSAD2 from normal control (NL, n = 6; unshaded squares) and EoE patients (EoE, n = 10; shaded circles) (D).Quantitative PCR for radical S-adenosyl methionine domain containing 2 (RSAD2) from nonsilencing control (NSC; black circles) and dehydrogenase E1 and transketolase domain–containing 1 (DHTKD1) shRNA–transduced (black triangles) EPC2 cells untreated or treated with IL-13 (100 ng/mL for 24 h) in the ALI system (E). Data in D are presented as mean ± SD, and data in E are presented as the mean ± SEM from 3 independent experiments performed in triplicate and are normalized to untreated nonsilencing control (NSC) cells. Statistical analyses used were unpaired t test with Welch’s correction (D) and 1-way ANOVA with Sidak multiple comparison test (E). NL, normal control. *P < 0.05, **P < 0.01.