Accelerating rare disease diagnostics by linking DNA and RNA through an explainable and interactive RNA-guided workflow.

WHY IT MATTERS

This workflow could speed up diagnosis for patients with undiagnosed rare diseases by combining DNA and RNA analysis, potentially reducing the time from symptom onset to genetic diagnosis.

Scientists created a new tool that helps doctors diagnose rare diseases by looking at both DNA and RNA (the instructions cells use to make proteins). The tool is better at handling differences in how genes work in different people and situations, making it easier to find which gene changes cause a patient's rare disease.

Accelerating rare disease diagnostics by linking DNA and RNA through an explainable and interactive RNA-guided workflow. Abstract: Challenges preventing mainstream use of RNA-sequencing (RNA-seq) in genome diagnostics are sources of biological and technical variation, typically caused by intrinsic differences in gene expression between tissue types, cellular conditions, and environmental factors. While machine learning methods may partially correct unwanted variation, interpreting RNA-seq data that are typically generated by different sources over time, which is a realistic scenario in healthcare, remains challenging and complex. 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 result is a streamlined implementation of OUTRIDER and FRASER, comp Authors: Maassen et al. Journal: NAR genomics and bioinformatics MeSH: Humans, Workflow, Rare Diseases, RNA, Sequence Analysis, RNA, DNA