Fig. 1 | Nature Communications

Fig. 1

From: Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions

Fig. 1

Overview of study design and analytical flow. Schematic outlining the clinical phenotyping, sample collections, RNA-sequencing, and analyses conducted. A discovery cohort consisting of 19 peanut allergic subjects, underwent physician-supervised, double-blind oral food challenges to both peanut and placebo, with the order of challenges randomized. For each subject, whole blood samples at baseline, 2 h, and 4 h were each collected during the peanut and placebo challenges. RNA-sequencing was performed on all samples and used for the following analyses outlined in gray: (1) linear mixed-effects model analyses to identify peanut genes (i.e., genes with expression changes in response to peanut, but not placebo, during acute peanut allergic reactions); (2) weighted gene coexpression network analysis (WGCNA) to identify modules of co-expressed genes as broader constructs of biologic function; and (3) leukocyte deconvolution analysis to identify cellular response during the acute peanut allergic reactions. Peanut genes identified by linear mixed-effects model analysis and WGCNA were projected onto a probabilistic causal gene network. Functional biologic processes implicated by WGCNA and peanut genes were investigated further using gene ontology enrichment analysis. Key driver analysis was implemented to identify key causal modulators of the peanut response module enriched for peanut genes. A replication cohort of 21 peanut allergic subjects analogously profiled was used to replicate major findings from this study (steps for which replication analyses were conducted are indicated with maroon arrows)

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