rewirebio.iobenchmarks
Evidence claim

Relevance of ABCA4 deep-intronic variants: classification against mini- or midigene splicing results (Riepe et al. Table 4) to "Prioritise variants for splicing experiments"

Use case
Prioritise variants for splicing experiments
Assessed by
ABCA4 deep-intronic variants: classification against mini- or midigene splicing results (Riepe et al. Table 4)
Relevance
Proxy evidence
Endpoint
Confusion matrix, accuracy, PPV, sensitivity, specificity, NPV and MCC for up to 11 splice predictors on 81 ABCA4 deep-intronic variants tested in mini- or midigene assays

Experimentally measured splicing of human SNVs, with several predictors scored on the same variants, informs which configurations to use when choosing SNVs for a follow-up splicing experiment. As for the existing MFASS mappings, transfer to a different assay, exon or follow-up capacity is not established.

9 reviewed evaluations

Evidence

Source checking verifies the cited claim or transcription. It does not establish independent reproduction.

Evidence table

Inspect claims, sources and review details

Trace each statement to its source and review. A context-only reference supports the record generally; it does not verify an individual field. Source checking does not reproduce an experiment.

One row per statement and cited source. Multiple citations are not independent evaluations. Shared locators are labelled explicitly.

20 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-11-02-a7f03c9e55a5
Property and statementOriginal source and locationReview and provenance
Citation locations
1 values
  • source id
    splicing-follow-up-20261009-source-riepe2021
    locator
    Table 4; Methods 'Datasets' and 'In silico splice prediction tools'
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.citation_locators

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Comparison group
riepe2021-minigene
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.comparison_group

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Comparison title
ABCA4 and MYBPC3 mini- and midigene variant sets (Riepe et al. 2021)
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.comparison_title

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Constraints
2 values
  • Inspect every linked evaluation's source locator and preserved conflicts before citing a result.
  • Do not combine this mapping's evaluations with any other protocol's results, including the matched and historical MFASS protocols; populations, labels and thresholds differ.
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.constraints

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Endpoint
Confusion matrix, accuracy, PPV, sensitivity, specificity, NPV and MCC for up to 11 splice predictors on 81 ABCA4 deep-intronic variants tested in mini- or midigene assays
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.endpoint

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Claimed field
links:assessed_by:splicing-follow-up-20261009-protocol-riepe2021-abca4-di
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.field

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Headline metric
matthews-correlation-coefficient
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.headline_metric

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Limitations
6 values
  • Variants were selected for testing with Alamut tools (ABCA4) or MaxEntScan (MYBPC3), which can favour those tools and their relatives.
  • Cutoffs appear to be tuned on the same data set (Table 2 ROC-optimal thresholds); Tables 3-5 do not state the cutoff, so values may be optimistic.
  • Small single-gene sets with strong class imbalance (ABCA4 NCSS 90% positive, ABCA4 DI 26% positive).
  • Variants are from patients but splicing was measured in mini- or midigene assays in HEK293T, not in patient tissue.
  • The authors note the selection bias but observed the opposite pattern (Alamut 3/4 best on MYBPC3).
  • Spidex's unscored variants are counted in its confusion matrix without a stated class.
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.limitations

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

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Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.pins

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

Rationale
Experimentally measured splicing of human SNVs, with several predictors scored on the same variants, informs which configurations to use when choosing SNVs for a follow-up splicing experiment. As for the existing MFASS mappings, transfer to a different assay, exon or follow-up capacity is not established.
Context-only references
Benchmarking deep learning splice prediction tools using functional splice assays

Original source ↗

splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'

Version: Human Mutation 42(7):799, published online 2021-05-20; PMC8360004 full-text XML
Retrieved: 2026-10-09T20:52:02Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.rationale

Source artifact SHA-256: 595be5360a9d3d421c4d4b6adda30175b4048e1aa0b563eb7afd2b7850277112

Hash scope: Hash scope not separately documented; inspect source record

Inspected artifact

How to read the evidence

Sources and history

Release 2026-11-02-a7f03c9e55a5 · Record review: source checked

1 source record and release historyDownload this release (gzip)
Technical metadata and extraction receipts

Stable ID: use-case-mapping-splicing-follow-up-20261009-riepe2021-abca4-di

field
links:assessed_by:splicing-follow-up-20261009-protocol-riepe2021-abca4-di
value
splicing-follow-up-20261009-protocol-riepe2021-abca4-di
relevance
proxy
endpoint
Confusion matrix, accuracy, PPV, sensitivity, specificity, NPV and MCC for up to 11 splice predictors on 81 ABCA4 deep-intronic variants tested in mini- or midigene assays
rationale
Experimentally measured splicing of human SNVs, with several predictors scored on the same variants, informs which configurations to use when choosing SNVs for a follow-up splicing experiment. As for the existing MFASS mappings, transfer to a different assay, exon or follow-up capacity is not established.
constraints
Inspect every linked evaluation's source locator and preserved conflicts before citing a result.; Do not combine this mapping's evaluations with any other protocol's results, including the matched and historical MFASS protocols; populations, labels and thresholds differ.
limitations
Variants were selected for testing with Alamut tools (ABCA4) or MaxEntScan (MYBPC3), which can favour those tools and their relatives.; Cutoffs appear to be tuned on the same data set (Table 2 ROC-optimal thresholds); Tables 3-5 do not state the cutoff, so values may be optimistic.; Small single-gene sets with strong class imbalance (ABCA4 NCSS 90% positive, ABCA4 DI 26% positive).; Variants are from patients but splicing was measured in mini- or midigene assays in HEK293T, not in patient tissue.; The authors note the selection bias but observed the opposite pattern (Alamut 3/4 best on MYBPC3).; Spidex's unscored variants are counted in its confusion matrix without a stated class.
citation locators
source id: splicing-follow-up-20261009-source-riepe2021; locator: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'
source locator
splicing-follow-up-20261009-source-riepe2021: Table 4; Methods 'Datasets' and 'In silico splice prediction tools'
revision
1
reason
Recorded from the splicing follow-up use-case pass 2026-10-09 (data/omics/use-case-coverage-splicing-follow-up-20261009/).
comparison group
riepe2021-minigene
comparison title
ABCA4 and MYBPC3 mini- and midigene variant sets (Riepe et al. 2021)
headline metric
matthews-correlation-coefficient
stratum label
ABCA4 deep-intronic variants
stratum order
2
reviewed evaluations
splicing-follow-up-20261009-eval-riepe2021-abca4-di-alamut-consensus; splicing-follow-up-20261009-eval-riepe2021-abca4-di-cadd-1-6; splicing-follow-up-20261009-eval-riepe2021-abca4-di-dssp; splicing-follow-up-20261009-eval-riepe2021-abca4-di-genesplicer; splicing-follow-up-20261009-eval-riepe2021-abca4-di-maxentscan; splicing-follow-up-20261009-eval-riepe2021-abca4-di-nnsplice; splicing-follow-up-20261009-eval-riepe2021-abca4-di-spliceai-1-3-1; splicing-follow-up-20261009-eval-riepe2021-abca4-di-splicerover; splicing-follow-up-20261009-eval-riepe2021-abca4-di-splicesitefinder-like
review
method: automated-source-review; reviewer: claude; reviewer note: Separate Claude review agent, independent of the extractor; no human review claimed; reviewed at: 2026-10-09T22:30:00Z; note: Independent review of endpoint fit, relevance grade, limitations and grouping against the use case and the source text; every value of the listed evaluations was checked against the pinned table. No execution, reproduction, human scientific review or clinical validation.
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