Relevance of Recovery of known pathogenic splicing events and outlier calls in true-negative samples, patient RNA-seq (Silverstein et al. Table S9, splicing tools) to "Select a patient-RNA splicing-variant validation workflow"

Stable ID: use-case-mapping-rna-splicing-20261011-silverstein2026-splicing

field

links:assessed_by:rna-splicing-20261011-silverstein2026-protocol-splicing

value

rna-splicing-20261011-silverstein2026-protocol-splicing

relevance

direct

endpoint

Per-tool TP, FN, TN and FP counts with accuracy, precision, recall, F1 and MCC for rMATS-turbo, MINTIE, FRASER, FRASER2.0 and LeafcutterMD on known pathogenic splicing events and true-negative samples

rationale

Direct: patient muscle and fibroblast RNA-seq, several splicing callers on the same diagnosed samples, scored on recovery of known pathogenic splicing events and on outlier calls in true-negative samples; it is known-event recovery, not diagnostic yield.

constraints

Inspect every linked evaluation's source locator and population 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.; Compare tools only where their populations match; Table S9 denominators differ by tool.

limitations

Denominators differ by tool: rMATS and MINTIE 23 positives (muscle and fibroblast), FRASER 68 and LeafcutterMD 67 (three tissue sets), FRASER2.0 16 (muscle only).; Splicing true positives require at least 3 split reads supporting the novel junction in manual IGV review, so events invisible in the RNA-seq data are not counted.; The authors did not develop rMATS-turbo, MINTIE, FRASER, LeafcutterMD, OUTRIDER or the DROP MAE module. ANEVA-h is the authors' own method: two of its authors (K. R. Ganapathy and S. Silverstein) are the first and third authors of reference 36, the ANEVA-h preprint, so the ANEVA-H row is recorded as author_reported.; Positives are counted per known event or gene, negatives per true-negative sample: a negative sample with any reported outlier counts as one false positive. Accuracy, precision and MCC therefore mix event-level and sample-level units (Methods 'True Positive and Negative Detection').; Variants with clinically interpretable mechanisms were selected; the authors state this favours clearly defined events and likely underestimates tool sensitivity, and that binary outlier scoring of negatives may overestimate false-positive rates and lowers MCC (Discussion, limitations paragraph).; Retrospective study of a single centre's neuromuscular cohort; no confidence intervals are printed.; Preprint (medRxiv v1), not peer reviewed.

citation locators

source id: rna-splicing-20261011-silverstein2026-source-tables-s1-s10; locator: Table S9 rows 2 to 6; source id: rna-splicing-20261011-silverstein2026-source-article; locator: Methods 'One vs All Splice Tools', 'Case vs Control Splice Tools', 'True Positive and Negative Detection' and 'Performance Metrics'

source locator

rna-splicing-20261011-silverstein2026-source-tables-s1-s10: Table S9 rows 2 to 6; rna-splicing-20261011-silverstein2026-source-article: Methods 'One vs All Splice Tools', 'Case vs Control Splice Tools', 'True Positive and Negative Detection' and 'Performance Metrics'

headline metric

recall

comparison group

silverstein2026-neuromuscular

comparison title

RNA-seq tools on known diagnoses and true-negative samples, neuromuscular patient RNA-seq (Silverstein et al. 2026)

stratum label

Aberrant-splicing callers

stratum order

1

reason

Recorded from the 2026-10-11 use-case literature pass (data/omics/use-case-coverage-rna-splicing-20261011-silverstein2026). Independently reviewed in docs/reviews/use-cases/splicing-cnv-use-cases-2026-10-12.md.

review

method: source-hash-verification; independent-cell-check; automated-source-review; scope-review; reviewer: claude; reviewer note: Independent Claude review agent reviewer-scnv; did not extract this batch; no human review claimed; date: 2026-10-12; artifact sha256: 8b987ac49f086adc0a191522436529a70f243505f7dda9926786004e15b4601c; retrieval url: https://www.medrxiv.org/content/early/2026/01/28/2026.01.27.26344940.source.xml; method note: Drafted by the collector agent uc-splicing-cnv from the pinned source.; note: Checked by reviewer-scnv against the pinned source; verdict in docs/reviews/use-cases/splicing-cnv-use-cases-2026-10-12.md and in this batch's review.md.

reviewed evaluations

rna-splicing-20261011-silverstein2026-eval-fraser; rna-splicing-20261011-silverstein2026-eval-fraser2-0; rna-splicing-20261011-silverstein2026-eval-leafcuttermd; rna-splicing-20261011-silverstein2026-eval-mintie; rna-splicing-20261011-silverstein2026-eval-rmats

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• subject: Select a patient-RNA splicing-variant validation workflow