Manual versus Talos reanalysis of 219 unresolved genomes after a mean 660 days (Kaschta et al. 2026)
New P/LP and VUS findings, case-category counts and review effort from manual and automated reanalysis of the same unresolved cases.
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2 recorded evaluations, 14 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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Protocol: Manual versus Talos reanalysis of 219 unresolved genomes after a mean 660 days (Kaschta et al. 2026) · Dataset: UKSH rare-disease genomes without a prior P/LP finding: 219 cases (Kaschta et al. 2026)
Sorted by Count (cases with a new P/LP finding) (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 | Count (cases with a new P/LP finding) | Count (cohort cases with a reported P/LP finding after reanalysis (158 before)) | Candidates per case (average variants returned per case, singleton and trio cases) | Count (cases with newly reported findings (P/LP or VUS)) | Count (cohort cases without a prioritised finding after reanalysis (170 before)) | Count (cohort cases without a reported clinically relevant finding after reanalysis (170 before)) | Count (of the two cases newly classified as VUS by manual reanalysis, cases also prioritised) | Diagnostic yield (total P/LP diagnostic rate in the 377-case cohort after reanalysis) | Review time per case (mean hands-on time for full manual case reanalysis, excluding report writing and secondary-review preparation) | Count (cohort cases with VUS findings after reanalysis (49 before)) | Count (cases newly classified as VUS findings) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Manual reanalysis in Illumina Emedgene with DRAGEN v4.2.4 re-calling (Kaschta et al. 2026)Evaluation | three (best in column) | 161 (best in column) | Not reported | five | Not reported | 166 | Not reported | 42.7% | 81 minutes | 50 | two |
| Talos 8.2.0 on archived DRAGEN v3.7.5 VCFs, pedigree where available (Kaschta et al. 2026)Evaluation | three (best in column) | 161 (best in column) | three | Not reported | 167 | Not reported | one | Not reported | Not reported | 49 | Not reported |
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Sources and history
Release 2026-10-10-cbb3da59bc08 · Record review: source checked
1 source record and release history
- Automated versus manual reanalysis in rare disease genomics · Original source · medRxiv 2026.05.16.26352295 v1, posted 2026-05-19; JATS source XML
Technical metadata and extraction receipts
Stable ID: reanalysis-kaschta-20261010-protocol-manual-vs-talos-219-reanalysis
- areas
- dna-genomes
- contexts
- clinical_research
- protocol
- Manual reanalysis of all 219 cases without a prior P/LP finding (October 2024 to December 2025); Talos applied to the whole cohort (October 2025); concordance defined as Talos returning the variants found or reclassified by manual reanalysis; outcomes counted at case level in the 377-case cohort.
- version
- medRxiv v1
- source locator
- Methods 'Study Cohort and Reanalysis Design', 'Manual Reanalysis', 'Automated Reanalysis Using Talos', 'Concordance Analysis and Error Types'; Results 'Reanalysis Diagnostic Yield'
- limitations
- Unequal inputs: the manual arm re-aligned and re-called the raw reads with DRAGEN v4.2.4 and used Emedgene; Talos used the archived DRAGEN v3.7.5 VCFs. Differences cannot be attributed to the method alone.; The reference is the manual arm's own result: Talos is scored on whether it returned what manual reanalysis found, so findings that only Talos might have made are not counted.; Very small numbers: three new P/LP cases in each arm.; The Talos total diagnostic yield is printed as 41.9% in a sentence that also gives 158 to 161 cases and calls it identical to the manual result; 161 of 377 is 42.7%, and 41.9% is the initial yield. That one result is disputed and not shown; the Talos count of 161 is stored.; Talos output per case is printed as an average of three variants (Results; Discussion P3) and as a median of approximately three (Discussion P1); the stored value is the average. It is a rounded word, and the cases it averages over (219 or the whole cohort) are not stated.; Manual time excludes report writing and preparation of evidence for secondary review; no hands-on time is printed for Talos.; Single centre, high initial yield (41.9%), one reanalysis round after a mean of 660 days.; A new candidate or classification is not a confirmed diagnosis; per-case confirmation details are in the supplement, which was not read.; Review effort is measured in different units: mean analyst minutes per case for the manual arm, candidate variants per case for Talos. No analyst time is printed for reviewing the Talos output, so the two cannot be compared as effort.; Manual reanalysis ran from October 2024 to December 2025 and Talos once in October 2025, so the knowledge available to each arm differed by case.; Illumina, which makes DRAGEN and Emedgene, provided sequencing reagents, software licences and technical support and supported the study (Competing interests; Funding statement).
Related records
- uses data: UKSH rare-disease genomes without a prior P/LP finding: 219 cases (Kaschta et al. 2026)
- subject: reported_finding: reanalysis-kaschta-20261010-protocol-manual-vs-talos-219-reanalysis
- subject: input_difference: reanalysis-kaschta-20261010-protocol-manual-vs-talos-219-reanalysis
- assessment: Manual reanalysis of 219 unresolved genomes
- assessment: Talos reanalysis of 219 unresolved genomes
- assessed by: Reanalyse unresolved rare-disease cases