Extended Data Fig. 5: Additional eQTL analysis.

Further characterization and stratification of AlphaGenome’s eQTL prediction performance. (a) Performance comparison on eQTL tasks (Coefficient Spearman R, Sign auROC, Causality auROC zero-shot, Causality RF auROC) across individual GTEx tissues (see Methods for specific scorer configurations). For zero-shot tasks, AlphaGenome’s default variant scorer is used (Methods; Fig. 4a). For the supervised causality task (‘eQTL Causality (RF)’), results use the best-performing feature set (‘All scorers combined’; e). For Borzoi comparison, the published L2_DIFF scorer across all output tracks is used. (b) Performance on eQTL tasks (Coefficient, Sign, Causality) stratified by distance from variant to target gene TSS, compared to Borzoi and a 1/distance baseline for the causality task. (c) Performance on eQTL tasks stratified by broad functional classes based on variant location. TG = Target Gene; VTG = Variant target gene. (d) Performance on indel eQTLs for the Sign and Coefficient tasks stratified by indel size, comparing AlphaGenome and Borzoi. (e) Random forest performance on the eQTL causality task using different feature sets. Horizontal bar plot compares RF performance (auROC from Fig. 4g) when trained using features derived from all scorers combined or individual modality scorers (also comparing AlphaGenome to Borzoi outputs). (f) Observed versus predicted eQTL log2 fold change plotted against variant-TSS distance (within 262 kb, ensuring target TSS is within receptive field context). Observed values are allelic log-fold changes from Mohammadi et al.⁵⁶, which were used to allow direct comparison with the scale of AlphaGenome’s predicted log-fold changes (Methods). (g) Sign accuracy as well as the fraction of eQTLs that pass a certain quantile-score cutoff visualized for all possible thresholds and four eQTL distance categories. The quantile score cutoff which leads to an overall (across distance bins) sign accuracy of 90% is highlighted. At this cutoff, sign accuracy is similar across distance categories, although recall is notably lower for distal variants. (h) Scatterplot comparing observed versus predicted effect sizes for 8,678 fine-mapped eQTLs filtered for high AlphaGenome prediction scores (>99th percentile of common variants). (i) Relationship between AlphaGenome’s quantile score threshold (x-axis; Methods) and the resulting performance (y-axis) for eQTL Sign accuracy and Coefficient Spearman R tasks.