ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Commonalities across computational workflows for uncovering explanatory variants in undiagnosed cases.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- 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
- VUStruct: A compute pipeline for high throughput and personalized structural biology.PLoS computational biology · 2026Article
- Phenotypic prediction of missense variants via deep contrastive learning.Nature biomedical engineering · 2026Article
- Toward a Genomics-Driven Hepatology: Liver Biology, Precision Diagnosis, and the Rise in Genetic Therapies.Pharmaceutics · 2026Review
- Recommendations for bioinformatics in clinical practice.Genome medicine · 2025Review
- VarPPUD: Pinpointing diagnostic variants from sets of prioritized, strong candidate variants.PLoS computational biology · 2025Article
- Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations.Nature communications · 2025Article
- Few shot learning for phenotype-driven diagnosis of patients with rare genetic diseases.NPJ digital medicine · 2025Article
- Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients.BioData mining · 2025Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.bioRxiv : the preprint server for biology · 2024Article
- Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- VarPPUD: Variant post prioritization developed for undiagnosed genetic disorders.medRxiv : the preprint server for health sciences · 2024Article
- Phenotypic overlap between rare disease patients and variant carriers in a large population cohort informs biological mechanisms.medRxiv : the preprint server for health sciences · 2024Article
- Dual diagnosis ofRare (Amsterdam, Netherlands) · 2024Article
- International Undiagnosed Diseases Programs (UDPs): components and outcomes.Orphanet journal of rare diseases · 2023Review
- Simulation of undiagnosed patients with novel genetic conditions.Nature communications · 2023Article
- In vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders.Frontiers in cell and developmental biology · 2023Article
- Genomic medicine for liver disease.Hepatology (Baltimore, Md.) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 20 institutions in 1 country.
Funding
Abstract
purposeGenomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful.
methodsWe collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network via meetings with bioinformaticians, online survey forms, and analyses of internal protocols.
resultsWe found that tools for processing genomic sequencing data can be grouped into four distinct categories. Whereas well-established practices exist for initial variant calling and quality control steps, there is substantial divergence across sites in later stages for variant prioritization and multimodal data integration, demonstrating a diversity of approaches for solving the most mysterious undiagnosed cases.
conclusionThe largest differences across diagnostic workflows suggest that advances in structural variant detection, noncoding variant interpretation, and integration of additional biomedical data may be especially promising for solving chronically undiagnosed cases.
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What OpenQuestion holds
Registered trials
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.