The DOI matches its Crossref record; 295 of the 295 references it cites were found in a registry or an index.
A guide for the diagnosis of rare and undiagnosed disease: beyond the exome
Open accessAbstract
Rare diseases affect 30 million people in the USA and more than 300–400 million worldwide, often causing chronic illness, disability, and premature death. Traditional diagnostic techniques rely heavily on heuristic approaches, coupling clinical experience from prior rare disease presentations with the medical literature. A large number of rare disease patients remain undiagnosed for years and many even die without an accurate diagnosis. In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25–35%) of undiagnosed patients, often with actionable findings. However, a large proportion of these patients remain undiagnosed. In this review, we focus on technologies that can be adopted if exome sequencing is unrevealing. We discuss the benefits of sequencing the whole genome and the additional benefit that may be offered by long-read technology, pan-genome reference, transcriptomics, metabolomics, proteomics, and methyl profiling. We highlight computational methods to help identify regionally distant patients with similar phenotypes or similar genetic mutations. Finally, we describe approaches to automate and accelerate genomic analysis. The strategies discussed here are intended to serve as a guide for clinicians and researchers in the next steps when encountering patients with non-diagnostic exomes.
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DNA language models are powerful predictors of genome-wide variant effects
Benegas, G., Batra, S. S., & Song, Y. S. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311219120 · Cited by 157
Rare disease diagnosis using knowledge guided retrieval augmentation for ChatGPT
Zelin, C., Chung, W. K., Jeanne, M., Zhang, G., & Weng, C. (2024) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2024.104702 · Cited by 47
Consequences of genetic variants in miRNA genes
Machowska, M., Galka-Marciniak, P., & Kozlowski, P. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.11.036 · Cited by 40
Few shot learning for phenotype-driven diagnosis of patients with rare genetic diseases
Alsentzer, E., Li, M. M., Kobren, S. N., Noori, A., Undiagnosed Diseases Network, Kohane, I. S., & Zitnik, M. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-01749-1 · Cited by 54
Metadata
- Authors
- Marwaha, S., Knowles, J. W., & Ashley, E. A.
- Venue
- Genome Medicine
- Published
- 2022-02-28
- Volume
- 14
- Issue
- 1
- Pages
- 23-23
- ISSN
- 1756-994X (ISSN-L)
- OpenAlex
- W4214613209
- Cited by
- 359
- References
- 295
- FWCI
- 42.27
- Type
- journal article
- Language
- en
- Open access
- gold
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