ArticleEuropean journal of human genetics : EJHG2021
Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.
Article in European journal of human genetics : EJHG, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- aiDIVA - hybrid AI for rare disease diagnostics using evidence-based, machine learning and language models.NPJ genomic medicine · 2026Article
- Article
- Skipping the Biopsy: Real-World Experience of Whole-Exome Sequencing as First-Tier Testing in Pediatric Muscular Disorders.International journal of molecular sciences · 2026Article
- Genomics workforce views on automating genomic reanalysis: trust, equity and governance.Human genetics · 2026Article
- Gene4Denovo2: an updated platform for human de novo mutations discovery and interpretation.Nucleic acids research · 2026Article
- Enhancing Molecular Diagnostic Accuracy in Genetic Eye Disorders Through a Personalized Re-Evaluation Strategy.Investigative ophthalmology & visual science · 2026Article
- Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.Genetics in medicine open · 2026Article
- A heterozygous 9q34 deletion encompassing SPTAN1 as a cause of distal myopathy.European journal of human genetics : EJHG · 2026Article
- Mitochondrial DNA disease discovery through evaluation of genotype and phenotype data: The Solve-RD experience.American journal of human genetics · 2025Article
- MOLGENIS VIP: an end-to-end DNA variant interpretation pipeline for research and diagnostics configurable to support rapid implementation of new methods.NAR genomics and bioinformatics · 2025Article
- Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes.Nature genetics · 2025Article
- Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.Nature medicine · 2025Article
- Reanalysis of genomic data in rare disease: current practice and attitudes among Australian clinical and laboratory genetics services.European journal of human genetics : EJHG · 2024Article
- Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes.European journal of human genetics : EJHG · 2024Article
- Variants in mitochondrial disease genes are common causes of inherited peripheral neuropathies.Journal of neurology · 2024Article
- Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.European journal of human genetics : EJHG · 2024Article
- Phenotypic similarity-based approach for variant prioritization for unsolved rare disease: a preliminary methodological report.European journal of human genetics : EJHG · 2024Article
- An interconnected data infrastructure to support large-scale rare disease research.GigaScience · 2024Article
- Increased Diagnostic Yield by Reanalysis of Whole Exome Sequencing Data in Mitochondrial Disease.Journal of neuromuscular diseases · 2024Article
- International Undiagnosed Diseases Programs (UDPs): components and outcomes.Orphanet journal of rare diseases · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
27 authors.
Funding
Abstract
Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics.
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