Supplementary Figure 1: Pilot analysis supporting principles used by Pi.

a, Schematic illustration of scoring for nearby genes (nGene) from GWAS summary data accounting for linkage disequilibrium (LD) structure and genomic organization. Considering genomic proximity, that is, a distance window for GWAS SNPs taking account of LD structure, and also considering genomic organization, that is, nearby genes and SNPs constrained to the same topologically associated domain (TAD). b, Simultaneous optimization of parameters regarding genomic influential range (distance and decay for nearby gene scoring) and network influential range (the restarting probability controlling the degree of network connectivity being exploited by random walk with restart), in terms of performance measured by area under the curve (AUC) separating gold standard positives (clinical proof-of-concept immune drug targets) and gold standard negatives (simulated genes unlikely to be drug targets). Clinical proof-of-concept immune drug targets are sourced from the ChEMBL database, defined as a collection of target genes of drugs with phase 2 concluded, moving into phase 3 and above in Pi immune traits. c, Enrichment analysis of approved immune drug targets (left), phase 3 and above immune drug targets (middle), and clinical proof-of-concept immune targets (right) in terms of chromatin conformation genes (cGene) by physical interaction and eQTL genes (eGene) by expression. Enrichment analysis is based on one-sided Fisher’s exact test, with the vertical line in grey indicating the false discovery rate (FDR) threshold at 0.05. d, The cGene scored considering the empirical cumulative distribution function (eCDF) of the significance/strength level linking an SNP to a gene. e, The methodological overview of incorporating colocalization analysis at the GWAS-eQTL integration step in the Pi pipeline, and how to estimate directionality and magnitude of effect.