Figure 5. Correlation of eQTLs, EBV, and ATP to inter- and intra-individual variation in RNA expression levels, and correlation of RNA expression levels to inter- and intra-individual variation in drug response.
Total variance for each of the 1000 “best-measured” genes was separated into inter- and intra- individual variance components (see Methods) using expression data from the 49 unrelated individuals measured twice at the Broad Institute on the Affymetrix platform. (A) 95 genes with eQTLs that explained >10% of expression variance (FDR<10%) in the WTSI dataset were selected (to maximize eQTL detection power) and the SNP genotype was included in the variance components model of the gene to “account” for its effect. −1 times the change in each variance component is plotted for each gene. As expected, the plot shows that that SNPs (which remain fixed across experiments) only explain inter-individual variation in expression. Grey dashed lines indicate the inter- and intra- 2.5% and 97.5%-tiles of the distribution of variance component change estimates when the entire analysis is repeated on a permuted dataset. (B) 125 genes correlated to EBV at rho2>.05 (FDR<10%) were selected and the EBV measurement was included in the variance components model of the gene to “account” for its effect. −1 times the change in each variance component is plotted for each gene. The plot shows that EBV is correlated to inter-individual differences in gene expression that persist across experiments, intra-individual fluctuation in gene expression between experiments, or both, depending on the gene in question. Grey dashed lines are as in (A). (C) 249 genes correlated to ATP at rho2>.05 (FDR<10%) were selected and the ATP measurement was included in the variance components model of the gene to “account” for its effect. −1 times the change in each variance component is plotted for each gene. The plot shows that ATP is correlated to inter-individual differences in gene expression that persist across experiments, intra-individual fluctuation in gene expression between experiments, or both, depending on the gene in question. Grey dashed lines are as in (A). (D) 202 “drug-response correlated” genes were defined as in Figure 6. The expression of each gene was incorporated in a variance components model of the assigned drug response EC50 to examine the correlation of the gene to its strongest correlated drug. −1 times the change in the variance components of drug response is plotted for each gene, showing that it is mostly the inter- individual differences in gene expression that are correlated to cell line drug response. Grey dashed lines are as in (A).