Measuring Co-expression of Drug Targets

We downloaded the RNA-seq data (RPKM value) across 32 tissues from GTEx V6 release (accessed on April 2016, https://gtexportal.org/). For each tissue, we regarded those genes with RPKM ≥ 1 in more than 80% samples as tissue-expressed genes. To measure the extent to which drug target-coding genes (a and b) associated with the drug-treated diseases are co-expressed, we calculated the Pearson’s correlation coefficient ( $PCC\left(a,b\right)$ ) and the corresponding P-value via F-statistics for each pair of drug target-coding genes a and b across 32 human tissues. In order to reduce the noise of co-expression analysis, we mapped PCC(a, b) into the human protein–protein interactome network (Supplementary Methods 2) to build a co-expressed protein–protein interactome network as described previously^{51 (link)}. The co-expression similarity of the drug target-coding genes associated with two drugs A and B is computed by averaging PCC(a,b) over all pairs of targets a and b with $a\in A$ and $b\in B$ as below: $⟨S_{\mathrm{co}}⟩=\frac{1}{n_{\mathrm{pairs}}}\sum _{\left\{a,b\right\}}\mid PCC\left(a,b\right)\mid$