ArticleAmerican journal of human genetics2025
Clinical validation of RNA sequencing for Mendelian disorder diagnostics.
Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Arriving at a diagnosis: Effective strategies used by the Undiagnosed Diseases Network.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Beyond in silico prediction: multi-omics to identify a pathogenic deep intronic HNRNPK variant in Au-Kline syndrome.Journal of human genetics · 2026Article
- When splicing is not all or none: GT>GC 5' splice-site variants as a model for intermediate effects and challenges in variant classification.HGG advances · 2026Article
- Evaluating the Utility of RNAseq in Prenatal Diagnostics: Expression Profiles of Cultured Chorionic Villus and Amniotic Fluid Samples.Prenatal diagnosis · 2026Article
- Translating transcriptomics analysis into diagnostic workflows: clinical variant identification and interpretation in hypothesis-driven and hypothesis-free approaches.EBioMedicine · 2026Article
- Fibroblast Transcriptomics in Molecular Diagnostics of a Comprehensive Dystonia Cohort.Annals of neurology · 2026Article
- Integrative Transcriptomic and Machine Learning Analysis of ecDNA-Associated Features for Studying Chemotherapy Resistance in TNBC.bioRxiv : the preprint server for biology · 2026Article
- A Homozygous Deep Intronic SNX14 Variant Activates Pseudo-Exon Inclusion in a Patient with SCAR20.Genes · 2026Article
- TEDD 2.0: an advanced temporal gene expression database enabled by in-silico functional analyses for developmental mechanism investigation.Science China. Life sciences · 2026Article
- Addressing the diagnostic gap through deep phenotyping.Human genomics · 2026Article
- Benchmarking RNA-seq Tools for Real-World Diagnostic Applications.Research square · 2026Article
- Benchmarking RNA-seq Tools for Real-World Diagnostic Applications.medRxiv : the preprint server for health sciences · 2026Article
- Genome and transcriptome sequencing reveal pathogenic activation of a pseudoexon inGenetics in medicine open · 2026Article
- TRACE: A Framework for Integrating Transcript Relevance Into ACMG/AMP Variant Interpretation.Human mutation · 2026Review
- A role forFrontiers in genetics · 2026Article
- RNA Sequencing Addresses a 5' UTR Variant Leading to X-Linked Agammaglobulinemia and Broader Immune Dysregulation.Journal of clinical immunology · 2025Article
- Long-range PCR and Nanopore sequencing for localisation and phasing variants: an end-to-end clinical application workflow.BMC medical genomics · 2025Article
- RNA sequencing provides functional insights and diagnostic resolution in previously unsolved rare disease cases.BMC medical genomics · 2025Article
- The utility of ultra-deep RNA sequencing in Mendelian disorder diagnostics.American journal of human genetics · 2025Article
- Oxford Nanopore Technologies [ONT] Sequencing: Clinical Validation in Genetically Heterogeneous Disorders.Genes · 2025Article
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15 authors.
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Abstract
Despite rapid advancements in clinical sequencing, over half of diagnostic evaluations still lack definitive results. RNA sequencing (RNA-seq) has shown promise in research settings for bridging this gap by providing essential functional data for accurate interpretation of diagnostic sequencing results. However, despite advanced research pipelines, clinical translation of diagnostic RNA-seq has not yet been realized. We have developed and validated a clinical diagnostic RNA-seq test for individuals with suspected genetic disorders who have existing or concurrent comprehensive DNA diagnostic testing. This diagnostic RNA-seq test processes RNA samples from fibroblasts or blood and derives clinical interpretations based on the analytical detection of outliers in gene expressions and splicing patterns. The clinical validation involves 130 samples, including 90 negative and 40 positive samples. We developed provisional expression and splicing benchmarks using short-read and long-read RNA-seq data from the GM24385 lymphoblastoid sample produced by the Genome in a Bottle Consortium. For clinical validation, we first established reference ranges for each gene and junction based on expression distributions from our control data. We then evaluated the clinical performance of our outlier-based pipeline using 40 positive samples with previously identified diagnostic findings from the Undiagnosed Diseases Network project. Our study provides a paradigm and necessary resources for independent laboratories to validate a clinical RNA-seq test.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.