Evidence claim

Relevance of RNA-seq confirmation of SpliceAI2-prioritised rare variants in panel genes, Genomics England rare-disease participants (SpliceAI2 paper) to use case use-case-patient-rna-splicing-validation

Use case: Select a patient-RNA splicing-variant validation workflow
Assessed by: RNA-seq confirmation of SpliceAI2-prioritised rare variants in panel genes, Genomics England rare-disease participants (SpliceAI2 paper)
Relevance: Proxy evidence
Endpoint: Number of rare variants prioritised by SpliceAI2 (> 0.25) in phenotype-matched panel genes and the number with RNA-seq evidence of the predicted splicing change (23 and 17)

Shows how often SpliceAI2-prioritised candidates in rare-disease participants were supported by the participant's own RNA-seq, the follow-up step this use case is about. Proxy: one tool only, a single threshold, and confirmation of a splicing change rather than a diagnosis.

1 reviewed evaluation

SpliceAI2 prioritised variants confirmed in Genomics England RNA-seq

Evidence

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19 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
Property and statement	Original source and location	Review and provenance
Citation locations 3 values source id rna-splicing-20261013-spliceai2-source-article locator Main 'Contribution to rare genetic disease' paragraph 4 source id rna-splicing-20261013-spliceai2-source-article locator Fig. 4h,i source id rna-splicing-20261013-spliceai2-source-article locator Extended Data Fig. 5 Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Comparison group spliceai2-2026-gel Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Comparison title DNA splice predictors against cryptic splicing in Genomics England rare-disease blood RNA-seq (SpliceAI2 paper, developer-reported) Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Constraints 3 values Inspect every linked evaluation's source locator and configuration before citing a result. Do not combine this mapping's evaluations with any other protocol's results; truth sets, inputs and metrics differ between sources. Do not read 17 of 23 as a precision for other tools; no comparator was put through the same prioritisation. Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.constraints` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Endpoint Number of rare variants prioritised by SpliceAI2 (> 0.25) in phenotype-matched panel genes and the number with RNA-seq evidence of the predicted splicing change (23 and 17) Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.endpoint` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Claimed field links:assessed_by:rna-splicing-20261013-spliceai2-protocol-gel-prioritised-confirmation Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.field` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Headline metric true-positive-count Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.headline_metric` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Limitations 6 values SpliceAI2 only; SpliceAI and Pangolin were not evaluated on this prioritisation. 23 variants; no confidence interval. Confirmation is shown with sashimi plots against 20 pooled controls; a numeric confirmation rule for these variants is not stated. Developer-reported; controlled-access Genomics England data (project 754). Training overlap: SpliceAI2 was trained on all human genes outside chromosomes 21 and 22. Preprint (bioRxiv v1), not peer reviewed. Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.limitations` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Pinned records 6 values record id rna-splicing-20261013-spliceai2-eval-gel-prioritised-confirmation-spliceai2-ensemble fields status links attributes.origin attributes.comparison sha256 f2bda936da8ac0ed2c6d73ff69262a5fb407bb21b71cdeeef0652ee881362303 record id rna-splicing-20261013-spliceai2-protocol-gel-prioritised-confirmation fields status name description facets source_ids links attributes sha256 dd23e40ab6b7b3771af1edf358599cd50c2b25417e304aaa812dfaa2a6c1f812 record id rna-splicing-20261013-spliceai2-result-gel-prioritised-confirmation-spliceai2-ensemble-confirmed-count fields status attributes.metric attributes.metric_qualifier attributes.printed_value attributes.numeric_value sha256 2c4a1b6a33bb06cdc5a2e5cbeab4dd048017052833e90fcf3c08b890c48797ae record id rna-splicing-20261013-spliceai2-result-gel-prioritised-confirmation-spliceai2-ensemble-prioritised-count fields status attributes.metric attributes.metric_qualifier attributes.printed_value attributes.numeric_value sha256 c2c8cd951bf6c410fa8f8aa18e8bdd3a526dec2e14eb5d88acd655a9e601960f record id rna-splicing-20261013-spliceai2-source-article fields status attributes.artifact_sha256 sha256 09442cd33f8941b2e764e137cb843ca4a962a185fba4f3d7419d13f1981a5de1 record id use-case-patient-rna-splicing-validation fields status name description facets attributes.question attributes.decision attributes.inputs attributes.output attributes.exclusions attributes.setting attributes.clinical_scope attributes.intended_users sha256 b85cad56e15fbfad66a2e70c3b193ed56c464e5e44b62a19b12f391e409ec897 Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.pins` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact
Rationale Shows how often SpliceAI2-prioritised candidates in rare-disease participants were supported by the participant's own RNA-seq, the follow-up step this use case is about. Proxy: one tool only, a single threshold, and confirmation of a splicing change rather than a diagnosis. Context-only references	A unified framework for quantitative splicing and transcript prediction (Jaganathan et al., bioRxiv 2026) Original source ↗ rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5 Version: bioRxiv preprint version 1, posted 2026-10-11; full-text PDF (57 pages) Retrieved: 2026-10-13T12:40:34Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.rationale` Source artifact SHA-256: `f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF when serving it (XMP ModifyDate, MetadataDate, DocumentID, InstanceID, Info ModDate and the second trailer ID), so later retrievals differ. A reviewer retrieval on 2026-10-13 of the same length (2,679,664 bytes) had SHA-256 407f5884427dda0226e0ce1f022e4479d3ff2b243da18bcc691eb345b0e04a6a and ModDate D:20261013063115-07'00'; its bytes differ only in those fields and its pdftotext text layer is identical to the pinned copy. Inspected artifact

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Release 2026-10-22-1b7cf027e4f6 · Record review: source checked

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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: use-case-mapping-rna-splicing-20261013-spliceai2-gel-prioritised

field: links:assessed_by:rna-splicing-20261013-spliceai2-protocol-gel-prioritised-confirmation
value: rna-splicing-20261013-spliceai2-protocol-gel-prioritised-confirmation
relevance: proxy
endpoint: Number of rare variants prioritised by SpliceAI2 (> 0.25) in phenotype-matched panel genes and the number with RNA-seq evidence of the predicted splicing change (23 and 17)
rationale: Shows how often SpliceAI2-prioritised candidates in rare-disease participants were supported by the participant's own RNA-seq, the follow-up step this use case is about. Proxy: one tool only, a single threshold, and confirmation of a splicing change rather than a diagnosis.
constraints: Inspect every linked evaluation's source locator and configuration before citing a result.; Do not combine this mapping's evaluations with any other protocol's results; truth sets, inputs and metrics differ between sources.; Do not read 17 of 23 as a precision for other tools; no comparator was put through the same prioritisation.
limitations: SpliceAI2 only; SpliceAI and Pangolin were not evaluated on this prioritisation.; 23 variants; no confidence interval.; Confirmation is shown with sashimi plots against 20 pooled controls; a numeric confirmation rule for these variants is not stated.; Developer-reported; controlled-access Genomics England data (project 754).; Training overlap: SpliceAI2 was trained on all human genes outside chromosomes 21 and 22.; Preprint (bioRxiv v1), not peer reviewed.
citation locators: source id: rna-splicing-20261013-spliceai2-source-article; locator: Main 'Contribution to rare genetic disease' paragraph 4; source id: rna-splicing-20261013-spliceai2-source-article; locator: Fig. 4h,i; source id: rna-splicing-20261013-spliceai2-source-article; locator: Extended Data Fig. 5
source locator: rna-splicing-20261013-spliceai2-source-article: Main 'Contribution to rare genetic disease' paragraph 4; rna-splicing-20261013-spliceai2-source-article: Fig. 4h,i; rna-splicing-20261013-spliceai2-source-article: Extended Data Fig. 5
comparison group: spliceai2-2026-gel
comparison title: DNA splice predictors against cryptic splicing in Genomics England rare-disease blood RNA-seq (SpliceAI2 paper, developer-reported)
stratum label: SpliceAI2-prioritised variants checked in RNA-seq
stratum order: 2
headline metric: true-positive-count
reason: Drafted from the 2026-10-13 SpliceAI2 extraction (data/omics/use-case-coverage-rna-splicing-20261013-spliceai2), issue #127. Independently reviewed in docs/reviews/use-cases/spliceai2-2026-10-13.md.
review: method: scope-review; independent-cell-check; reviewer: claude; reviewer note: Claude (Opus 5.5) research agent, independent reviewer; did not extract this batch; no human review claimed; date: 2026-10-13; artifact sha256: f8f3db2c3943d4827b670bc2e962e0cec8fbe96e0b1acf9d4a9b9f0c7a78c06b; retrieval url: https://www.biorxiv.org/content/10.64898/2026.10.08.757673v1.full.pdf; method note: Judged against the use case's question, inputs and output in data/entities/use-cases.jsonl and the existing judgements for the same use case; endpoint, limitations and every evaluation on the protocol re-read in the pinned PDF.; note: Checked against the pinned source by the independent reviewer; verdict and correction list in docs/reviews/use-cases/spliceai2-2026-10-13.md and this batch's review.json. Developer-reported value, not reproduced. Extraction method: Drafted by the extractor against the use case's question, inputs and output and the existing judgements for the same use case; not a review.
reviewed evaluations: rna-splicing-20261013-spliceai2-eval-gel-prioritised-confirmation-spliceai2-ensemble
pins: record id: rna-splicing-20261013-spliceai2-eval-gel-prioritised-confirmation-spliceai2-ensemble; fields: status; links; attributes.origin; attributes.comparison; sha256: f2bda936da8ac0ed2c6d73ff69262a5fb407bb21b71cdeeef0652ee881362303; record id: rna-splicing-20261013-spliceai2-protocol-gel-prioritised-confirmation; fields: status; name; description; facets; source_ids; links; attributes; sha256: dd23e40ab6b7b3771af1edf358599cd50c2b25417e304aaa812dfaa2a6c1f812; record id: rna-splicing-20261013-spliceai2-result-gel-prioritised-confirmation-spliceai2-ensemble-confirmed-count; fields: status; attributes.metric; attributes.metric_qualifier; attributes.printed_value; attributes.numeric_value; sha256: 2c4a1b6a33bb06cdc5a2e5cbeab4dd048017052833e90fcf3c08b890c48797ae; record id: rna-splicing-20261013-spliceai2-result-gel-prioritised-confirmation-spliceai2-ensemble-prioritised-count; fields: status; attributes.metric; attributes.metric_qualifier; attributes.printed_value; attributes.numeric_value; sha256: c2c8cd951bf6c410fa8f8aa18e8bdd3a526dec2e14eb5d88acd655a9e601960f; record id: rna-splicing-20261013-spliceai2-source-article; fields: status; attributes.artifact_sha256; sha256: 09442cd33f8941b2e764e137cb843ca4a962a185fba4f3d7419d13f1981a5de1; record id: use-case-patient-rna-splicing-validation; fields: status; name; description; facets; attributes.question; attributes.decision; attributes.inputs; attributes.output; attributes.exclusions; attributes.setting; attributes.clinical_scope; attributes.intended_users; sha256: b85cad56e15fbfad66a2e70c3b193ed56c464e5e44b62a19b12f391e409ec897

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