Supplementary Figure 7: Relevant tissue networks show the best performance in reprioritizing hypertension GWAS and are enriched with targets of antihypertensive drugs.
From: Understanding multicellular function and disease with human tissue-specific networks
To evaluate the choice of tissues for reprioritization, we evaluated all tissue networks (along with the tissue-naive network) in the same setting we used for the kidney network. (a) The distribution of performance (measured using AUC) shows that the right tissue network, kidney, and other relevant tissues, heart and liver, are among the best, while the tissue-naive network sits amidst tissue networks that provide an average performance. (b) Top-ranked genes by NetWAS are significantly enriched with targets of antihypertensive drugs. Drug targets were obtained from four databases—DrugBank, TTD, PharmGKB and CTD—which curate this information using different criteria. We evaluated both the original GWAS (gray) and NetWAS using the kidney network (dark red) for enrichment of drug targets from each of these sources among the top-ranked genes. Enrichment was measures using z scores (Online Methods), with higher scores indicating greater enrichment near the top of the list. In nearly all cases—target data sources and phenotypic end points—NetWAS reprioritization resulted in significant top ranking of therapeutic targets, over the original GWAS.
