The workflow links DNA and RNA to identify gene-disease associations and prioritize patient-level variants in rare disease diagnostics. It uses interactive reports to visualize outlier genes and prioritized variants for clinical interpretation.
First-pass extracted concept
RNA-guided workflow
Candidate: workflow template1 source documents6 linked claims1 workflow observations
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Workflow Logic
Workflow evidenceSource 1
Objective: Use an explainable and interactive RNA-guided workflow to link DNA and RNA for rare disease diagnostics and identify gene-disease associations.
Why it works: The workflow is described as handling biological and technical variation in RNA-seq and combining expression and splicing outlier analysis with genomic, phenotypic, and segregation analysis to support clinical interpretation.
Priority logic: The workflow prioritizes outlier genes and patient-level variants for immediate clinical interpretation, aiming to accelerate coding and non-coding variant prioritization and VUS reclassification.
Validation strategy: The abstract reports analysis of 144 cases from different centres to demonstrate that RNA outlier analysis enhances variant interpretation.
Target properties: robustness to biological variation, robustness to technical variation, variant prioritization, clinical interpretability, detection of expression effects, detection of splicing effects
Target mechanisms: pinpointing rare variants affecting gene expression, pinpointing rare variants affecting splicing, linking RNA outliers to genomic and phenotypic interpretation
Target techniques: RNA-seq outlier analysis, integration of genomic, phenotypic, and segregation analysis, interactive report generation
Evidence Snippets
Supporting Sources
Linked Claims
The study analyzed 144 cases from different centres.
Quoted textsource-backed
We analysed 144 cases from different centres, a realistic cohort for centres more likely to be dependent on background cohorts.
The workflow accelerates prioritization of coding and non-coding variants and reclassification of clinically relevant variants of unknown significance.
Quoted textsource-backed
Our workflow accelerates the prioritization of coding and non-coding variants, and the reclassification of clinically relevant variants of unknown significance.
RNA outlier analysis enhances variant interpretation and can aid clinical variant interpretation despite limitations.
Quoted textsource-backed
We demonstrate that RNA outlier analysis enhances variant interpretation and, despite its limitations, is already able to aid clinical variant interpretation.
The paper reports a complete RNA-guided workflow that handles biological and technical variation in RNA-seq data and can identify gene-disease associations in rare disease patients when integrated with genomic, phenotypic, and segregation analysis.
Quoted textsource-backed
We developed a complete RNA-guided workflow that handles such variation and is therefore able to identify gene-disease associations in the context of genomic, phenotypic, and segregation analysis of rare disease patients.
The reported RNA-guided workflow is composed of a streamlined implementation of OUTRIDER and FRASER complemented with Borzoi and MOLGENIS VIP.
Quoted textsource-backed
The result is a streamlined implementation of OUTRIDER and FRASER, complemented with Borzoi and MOLGENIS VIP.
The workflow enables pinpointing rare variants affecting gene expression and splicing using self-contained interactive reports that visualize outlier genes and prioritized patient-level variants for immediate clinical interpretation.
Quoted textsource-backed
This novel workflow paves the way for pinpointing rare variants affecting gene expression and splicing using self-contained interactive reports visualizing outlier genes and prioritized patient-level variants for immediate clinical interpretation.