Fig. 4: Validation of SNPs prioritized by PENGUIN.

CRISPR/Cas9 knockout and RNAi screens provide Z-scores to quantify the relevance of a specific gene network to proliferation of LNCaP cells. A CRISPR/Cas9 knockout analysis indicates that intermediate SNPs prioritized by PENGUIN (red) occur in genes essential for LNCaP. Genes with the strongest effect are labeled. B RNAi analysis shows milder but significantly consistent results with CRISPR/Cas9 knockout. A, B The boxes show the interquartile range (IQR), the central line represents the median, the whiskers add 1.5 times the IQR to the 75 percentile (box upper limit) and subtract 1.5 times the IQR from the 25 percentile (box lower limit). Significance calculated with two-sided Mann–Whitney test. C Gene Set Enrichment Analysis (GSEA) indicates that SNPs prioritized by PENGUIN occur in the most essential genes identified by CRISPR/Cas9 knockouts. D GSEA indicates that SNPs prioritized by PENGUIN occur in the most essential ones based on the RNAi screen. for C and D, the statistical significance of the enrichment of a gene set within the ranked gene list is reported. C, D Significance is calculated using a two-sided hypergeometric test. Source data are provided as a Source Data file and Supplementary Data 10.