Protocol

Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC)

Separate 4,545 RNA-seq-confirmed cryptic splice gains from 573,967 null GT/AG-creating variants by model score.

Overview

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Consult the linked sources for architecture or protocol details. Missing evidence is not evidence of a missing capability.

5 recorded evaluations, 17 metric rows. A comparison chart has not yet been validated for these results. The table retains the individual findings and their sources.

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Results

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All evaluations

5 evaluations · 17 results. Different protocols are not a single leaderboard.

Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) · Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)

Sorted by AUPRC (all variants; essential splice variants excluded) (higher is better). The best value in each column is highlighted. Decimals are rounded for display; each value links to the printed value and its source.

Tested configuration	AUPRC (all variants; essential splice variants excluded)	AUPRC (deep intronic variants (500 bp or more from the nearest exon); essential splice variants excluded)	AUPRC (exonic variants; essential splice variants excluded)	AUPRC (near intronic variants (under 500 bp from the nearest exon); essential splice variants excluded)
SpliceAI2 two-model multispecies ensemble (Jaganathan et al. 2026)Evaluation	0.77 (best in column)	0.68 (best in column)	0.8 (best in column)	0.79 (best in column)
SpliceAI 1.3.1, position-resolved delta at the effect position, masking off (Jaganathan et al. 2026)Evaluation	0.66	0.52	0.73	0.7
AlphaGenome raw splice site score, maximum aggregation (Jaganathan et al. 2026)Evaluation	0.63	Not reported	Not reported	Not reported
Pangolin, per-position score at the effect position, masking off (Jaganathan et al. 2026)Evaluation	0.56	0.44	0.64	0.67
AlphaGenome raw composite splice score, maximum aggregation (Jaganathan et al. 2026)Evaluation	0.54	0.45	0.56	0.58

All 17 result rows with coverage, uncertainty and sources

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Tested model or methodProtocolDatasetEvaluation setupMetricEvidence origin

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Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: AlphaGenome raw composite splice score, maximum aggregation (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.54 AUPRC (all variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaGenome on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'AlphaGenome', column 'All'
Configuration: AlphaGenome raw composite splice score, maximum aggregation (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.45 AUPRC (deep intronic variants (500 bp or more from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaGenome on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'AlphaGenome', column 'Deep intronic'
Configuration: AlphaGenome raw composite splice score, maximum aggregation (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.56 AUPRC (exonic variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaGenome on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'AlphaGenome', column 'Exon'
Configuration: AlphaGenome raw composite splice score, maximum aggregation (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.58 AUPRC (near intronic variants (under 500 bp from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaGenome on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'AlphaGenome', column 'Near intronic'
Configuration: AlphaGenome raw splice site score, maximum aggregation (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.63 AUPRC (all variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaGenome raw splice site score on GTEx GT/AG (auPRC, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Methods 'Evaluation of competing methods', AlphaGenome paragraph: '... GTEx GT/AG auPRC (0.63) ...'
Configuration: Pangolin, per-position score at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.56 AUPRC (all variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'Pangolin', column 'All'
Configuration: Pangolin, per-position score at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.44 AUPRC (deep intronic variants (500 bp or more from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'Pangolin', column 'Deep intronic'
Configuration: Pangolin, per-position score at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.64 AUPRC (exonic variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'Pangolin', column 'Exon'
Configuration: Pangolin, per-position score at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.67 AUPRC (near intronic variants (under 500 bp from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'Pangolin', column 'Near intronic'
Configuration: SpliceAI 1.3.1, position-resolved delta at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.66 AUPRC (all variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI', column 'All'
Configuration: SpliceAI 1.3.1, position-resolved delta at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.52 AUPRC (deep intronic variants (500 bp or more from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI', column 'Deep intronic'
Configuration: SpliceAI 1.3.1, position-resolved delta at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.73 AUPRC (exonic variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI', column 'Exon'
Configuration: SpliceAI 1.3.1, position-resolved delta at the effect position, masking off (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.7 AUPRC (near intronic variants (under 500 bp from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI', column 'Near intronic'
Configuration: SpliceAI2 two-model multispecies ensemble (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.77 AUPRC (all variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI2 on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI2', column 'All'
Configuration: SpliceAI2 two-model multispecies ensemble (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.68 AUPRC (deep intronic variants (500 bp or more from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI2 on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI2', column 'Deep intronic'
Configuration: SpliceAI2 two-model multispecies ensemble (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.8 AUPRC (exonic variants; essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI2 on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI2', column 'Exon'
Configuration: SpliceAI2 two-model multispecies ensemble (Jaganathan et al. 2026)	Protocol: Cryptic splice site activation by rare GT/AG-creating SNVs, GTEx WGS and RNA-seq (SpliceAI2 paper, auPRC) Dataset: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)	0.79 AUPRC (near intronic variants (under 500 bp from the nearest exon); essential splice variants excluded) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source SpliceAI2 on GTEx GT/AG (auprc, SpliceAI2 paper) rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection Aggregation: Not reported A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Extended Data Fig. 2 (page 52), panel 'GTEx GT/AG (auPRC)', row 'SpliceAI2', column 'Near intronic'

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A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) · Original source · bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages)

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Technical metadata and extraction receipts

Stable ID: rna-splicing-20261013-spliceai2-protocol-gtex-gtag-detection

areas: dna-genomes; rna-transcriptomes
contexts: research
protocol: Score every rare GT/AG-creating SNV with each model at the created site; compute auPRC for cryptic gains against nulls, overall and by region (exonic, near intronic, deep intronic >= 500 bp from the nearest exon).
version: bioRxiv v1 Extended Data Fig. 2 and Fig. 1d
metric: auprc
metric direction: higher
source locator: Methods 'Variant effect benchmarks' (GTEx and GEL GT/AG); Extended Data Fig. 2 panel 'GTEx GT/AG (auPRC)'; Fig. 1d
limitations: Null variants require at least ten carriers and high gene expression, so the class balance (4,545 of 578,512) and auPRC depend on those filters.; Region stratum sizes are not printed.; Developer-reported: the SpliceAI2 authors (Illumina) built the benchmark, chose comparator settings and ran every model; AlphaGenome was scored by co-authors at the University of Oxford.; Training overlap: SpliceAI2 was trained on all human genes except those on chromosomes 21 and 22, and the benchmark is genome-wide, so most variants lie in genes seen in training. Supplementary Table 1 lists GTEx among the recount3 human training sources.; Essential splice variants are excluded, so results do not cover canonical GT/AG disruption.; No confidence intervals or resampling uncertainty are printed.; Preprint (bioRxiv v1), not peer reviewed.

Related records

uses data: GTEx rare GT/AG-creating SNVs with RNA-seq cryptic splicing labels (Jaganathan et al. 2026)
assessment: AlphaGenome on GTEx GT/AG (auprc, SpliceAI2 paper)
assessment: AlphaGenome raw splice site score on GTEx GT/AG (auPRC, SpliceAI2 paper)
assessment: Pangolin on GTEx GT/AG (auprc, SpliceAI2 paper)
assessment: SpliceAI on GTEx GT/AG (auprc, SpliceAI2 paper)
assessment: SpliceAI2 on GTEx GT/AG (auprc, SpliceAI2 paper)

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