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AlphaGenome Nature 2026 supplementary methods

Supplement to Nature version of record, 28 January 2026; content hash pinned

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Model or configurationMetricValueDatasetEvaluation
AbSplice: retrained AbSplice (paper Table 4)AUPRC0.251 unitlessSupervised GTEx splicing-outlier prediction: evaluated data subsetAbSplice: retrained AbSplice (paper Table 4): Supervised GTEx splicing-outlier prediction
AlphaGenome absolute multimodal scores → RandomForestClassifierAUROC (tissue-weighted mean)0.80 unitlessSupervised distance-balanced eQTL causality: evaluated data subsetAlphaGenome absolute multimodal scores → RandomForestClassifier: Supervised distance-balanced eQTL causality
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.57 unitlessATAC track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: ATAC track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.74 unitlessCAGE track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: CAGE track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.86 unitlessDNase track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: DNase track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.69 unitlesshistone ChIP-seq track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: histone ChIP-seq track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.78 unitlessRNA-seq track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: RNA-seq track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching headPearson0.55 unitlessTF ChIP-seq track prediction at 32 bp: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with 32 bp Borzoi-matching head: TF ChIP-seq track prediction at 32 bp
AlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq headPearson (1 bp, linear scale)0.59 unitlessBase-resolution RNA-seq prediction: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq head: Base-resolution RNA-seq prediction
AlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq headPearson (1 bp, log1p scale)0.80 unitlessBase-resolution RNA-seq prediction: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq head: Base-resolution RNA-seq prediction
AlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq headPearson (gene tpm, across genes)0.80 unitlessRNA expression correlation across genes: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq head: RNA expression correlation across genes
AlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq headPearson (normalised gene tpm, across genes)0.52 unitlessRNA expression correlation across genes: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq head: RNA expression correlation across genes
AlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq headPearson (normalised gene tpm, across tracks)0.57 unitlessRNA expression correlation across tracks: evaluated data subsetAlphaGenome Borzoi-fold-1 model fine-tuned with base-resolution Borzoi RNA-seq head: RNA expression correlation across tracks
AlphaGenome distilled all-fold studentAUPRC0.56 unitlessAfrican-ancestry LCL caQTL classification: evaluated data subsetAlphaGenome distilled all-fold student: African-ancestry LCL caQTL classification
AlphaGenome distilled all-fold studentPearson0.74 unitlessAfrican-ancestry LCL caQTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: African-ancestry LCL caQTL effect-size prediction
AlphaGenome distilled all-fold studentAUPRC (all tissues pooled)0.51 unitlessAuthor MFASS splice-disruption prediction: evaluated data subsetAlphaGenome distilled all-fold student: Author MFASS splice-disruption prediction
AlphaGenome distilled all-fold studentPearson0.69 unitlessCoronary smooth-muscle caQTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: Coronary smooth-muscle caQTL effect-size prediction
AlphaGenome distilled all-fold studentAUPRC (max absolute track aggregation)0.66 unitlessDeep intronic and synonymous variants splicing-based classification: evaluated data subsetAlphaGenome distilled all-fold student: Deep intronic and synonymous variants splicing-based classification
AlphaGenome distilled all-fold studentAUPRC0.36 unitlessEuropean-ancestry LCL caQTL classification: evaluated data subsetAlphaGenome distilled all-fold student: European-ancestry LCL caQTL classification
AlphaGenome distilled all-fold studentPearson0.59 unitlessEuropean-ancestry LCL caQTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: European-ancestry LCL caQTL effect-size prediction
AlphaGenome distilled all-fold studentPearson0.64 unitlessMicroglia caQTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: Microglia caQTL effect-size prediction
AlphaGenome distilled all-fold studentAUPRC (max absolute track aggregation)0.18 unitlessMissense variants splicing-based classification: evaluated data subsetAlphaGenome distilled all-fold student: Missense variants splicing-based classification
AlphaGenome distilled all-fold studentAUPRC (pas distance 10000, mean over permutations)0.63 unitlessPolyadenylation-QTL causality: evaluated data subsetAlphaGenome distilled all-fold student: Polyadenylation-QTL causality
AlphaGenome distilled all-fold studentAUPRC0.50 unitlessSPI1 binding QTL classification: evaluated data subsetAlphaGenome distilled all-fold student: SPI1 binding QTL classification
AlphaGenome distilled all-fold studentPearson0.55 unitlessSPI1 binding QTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: SPI1 binding QTL effect-size prediction
AlphaGenome distilled all-fold studentAUPRC (max absolute track aggregation)0.57 unitlessSplice-site-region variants splicing-based classification: evaluated data subsetAlphaGenome distilled all-fold student: Splice-site-region variants splicing-based classification
AlphaGenome distilled all-fold studentAUPRC (tissue-weighted mean)0.76 unitlessSplicing-QTL causality: evaluated data subsetAlphaGenome distilled all-fold student: Splicing-QTL causality
AlphaGenome distilled all-fold studentAUPRC0.63 unitlessYoruba LCL dsQTL classification: evaluated data subsetAlphaGenome distilled all-fold student: Yoruba LCL dsQTL classification
AlphaGenome distilled all-fold studentPearson0.83 unitlessYoruba LCL dsQTL effect-size prediction: evaluated data subsetAlphaGenome distilled all-fold student: Yoruba LCL dsQTL effect-size prediction
AlphaGenome distilled all-fold studentAUROC (tissue-weighted mean)0.71 unitlessZero-shot distance-balanced eQTL causality: evaluated data subsetAlphaGenome distilled all-fold student: Zero-shot distance-balanced eQTL causality
AlphaGenome distilled all-fold studentAUPRC0.75 unitlessZero-shot enhancer–gene linking: evaluated data subsetAlphaGenome distilled all-fold student: Zero-shot enhancer–gene linking
AlphaGenome distilled all-fold studentAUPRC0.22 unitlessZero-shot GTEx splicing-outlier prediction: evaluated data subsetAlphaGenome distilled all-fold student: Zero-shot GTEx splicing-outlier prediction
AlphaGenome distilled cell-type-matched DNase scorer, Borzoi-matched locus subsetPearson (mean over loci or contexts)0.56 unitlessZero-shot CAGI5 MPRA activity-effect prediction (borzoi-ensemble-matched comparison): evaluated data subsetAlphaGenome distilled cell-type-matched DNase scorer, Borzoi-matched locus subset: Zero-shot CAGI5 MPRA activity-effect prediction (borzoi-ensemble-matched comparison)
AlphaGenome distilled cell-type-matched DNase scorer, ChromBPNet-matched locus subsetPearson (mean over loci or contexts)0.55 unitlessZero-shot CAGI5 MPRA activity-effect prediction (chrombpnet-matched comparison): evaluated data subsetAlphaGenome distilled cell-type-matched DNase scorer, ChromBPNet-matched locus subset: Zero-shot CAGI5 MPRA activity-effect prediction (chrombpnet-matched comparison)
AlphaGenome distilled multimodal DNase, RNA-seq and histone ChIP-seq features → per-locus LassoCVPearson (lasso on dnase, RNA and chip features)0.65 unitlessSupervised multimodal CAGI5 MPRA prediction: evaluated data subsetAlphaGenome distilled multimodal DNase, RNA-seq and histone ChIP-seq features → per-locus LassoCV: Supervised multimodal CAGI5 MPRA prediction
AlphaGenome Enformer-split model with 128 bp Enformer headPearson0.72 unitlessATAC track prediction at 128 bp: evaluated data subsetAlphaGenome Enformer-split model with 128 bp Enformer head: ATAC track prediction at 128 bp
AlphaGenome Enformer-split model with 128 bp Enformer headPearson0.71 unitlessCAGE track prediction at 128 bp: evaluated data subsetAlphaGenome Enformer-split model with 128 bp Enformer head: CAGE track prediction at 128 bp
AlphaGenome Enformer-split model with 128 bp Enformer headPearson0.87 unitlessDNase track prediction at 128 bp: evaluated data subsetAlphaGenome Enformer-split model with 128 bp Enformer head: DNase track prediction at 128 bp
AlphaGenome Enformer-split model with 128 bp Enformer headPearson0.71 unitlesshistone ChIP-seq track prediction at 128 bp: evaluated data subsetAlphaGenome Enformer-split model with 128 bp Enformer head: histone ChIP-seq track prediction at 128 bp
AlphaGenome Enformer-split model with 128 bp Enformer headPearson0.58 unitlessTF ChIP-seq track prediction at 128 bp: evaluated data subsetAlphaGenome Enformer-split model with 128 bp Enformer head: TF ChIP-seq track prediction at 128 bp
AlphaGenome ensemble of four fold-1 modelsAUPRC0.82 unitlessHuman splice-site classification: annotation-derived: evaluated data subsetAlphaGenome ensemble of four fold-1 models: Human splice-site classification: annotation-derived
AlphaGenome ensemble of four fold-1 modelsAUPRC0.79 unitlessHuman splice-site classification: RNA-derived: evaluated data subsetAlphaGenome ensemble of four fold-1 models: Human splice-site classification: RNA-derived
AlphaGenome fold-0 contact-map model, bilinearly resized to Orca 4 kb binsPearson (cell-type difference, 4 kb)0.42 unitlessCell-type difference in chromatin contact-map prediction: evaluated data subsetAlphaGenome fold-0 contact-map model, bilinearly resized to Orca 4 kb bins: Cell-type difference in chromatin contact-map prediction
AlphaGenome fold-0 contact-map model, bilinearly resized to Orca 4 kb binsPearson (per cell type, 4 kb)0.79 unitlesschromatin contact-map prediction: evaluated data subsetAlphaGenome fold-0 contact-map model, bilinearly resized to Orca 4 kb bins: chromatin contact-map prediction
AlphaGenome fold-0 track model on comparator-matched test peaksJensen shannon divergence (profile)0.46 unitlessATAC prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: ATAC prediction on held-out peaks
AlphaGenome fold-0 track model on comparator-matched test peaksPearson0.86 unitlessATAC prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: ATAC prediction on held-out peaks
AlphaGenome fold-0 track model on comparator-matched test peaksPearson (log total counts per peak)0.85 unitlessATAC prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: ATAC prediction on held-out peaks
AlphaGenome fold-0 track model on comparator-matched test peaksJensen shannon divergence (profile)0.51 unitlessDNase prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: DNase prediction on held-out peaks
AlphaGenome fold-0 track model on comparator-matched test peaksPearson0.75 unitlessDNase prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: DNase prediction on held-out peaks
AlphaGenome fold-0 track model on comparator-matched test peaksPearson (log total counts per peak)0.79 unitlessDNase prediction on held-out peaks: evaluated data subsetAlphaGenome fold-0 track model on comparator-matched test peaks: DNase prediction on held-out peaks

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AlphaGenome Nature 2026 supplementary methods

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86b2e6a07543e3c201e2e157a3e9c6eb5235ff13eb8a5224f6fcb6fe1808d4c0
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AlphaGenome Nature 2026 supplementary methods

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AlphaGenome Nature 2026 supplementary methods

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Supplement to Nature version of record, 28 January 2026; content hash pinned
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