ArticleScience translational medicine2019
Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 150 papers, 3 of them syntheses that pooled it.
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.
Genomic Biorepository: Protocol for the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data
Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data
Who cites it
150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 293 citations in OpenAlex.
- Pooled it
- Pediatric Predictive Artificial Intelligence Implemented in Clinical Practice from 2010 to 2021: A Systematic Review.Applied clinical informatics · 2025Pooled it
- The Potential of Research Drawing on Clinical Free Text to Bring Benefits to Patients in the United Kingdom: A Systematic Review of the Literature.Frontiers in digital health · 2021Pooled it
- Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Trial
- A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants.American journal of human genetics · 2020Trial
- An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm.American journal of human genetics · 2020Trial
- A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants.American journal of human genetics · 2019Trial
- Artificial Intelligence in Clinical Genetics: Current Applications and Challenges.Indian journal of pediatrics · 2026Review
- RankVar: machine learning-based variant ranking and reinterpretation for rare genetic diseases.Genome medicine · 2026Article
- Role of next generation sequencing in neonatal diagnosis and screening.Journal of neuromuscular diseases · 2026Review
- G.AI: an AI-driven platform for phenotype standardization, variant interpretation and structured clinical reporting in rare disease genomic diagnosis.Journal of translational medicine · 2026Article
- Diagnostic Yield After Postnatal Reanalysis of Prenatal Exome Sequencing Results.Prenatal diagnosis · 2026Article
- Genome-based medicine in Korea: the Korea National Institute of Health infrastructure for precision medicine.Childhood kidney diseases · 2026Review
- The transformative impact of ultra-rapid nanopore sequencing in precision medicine.Frontiers in immunology · 2026Review
- Diagnostic Yield of Genome Sequencing in an Iranian Exome-Negative Autosomal-Recessive Intellectual Disability Cohort.Human mutation · 2026Article
- Clinical risk factors predicting likelihood of pathogenic genetic result in NICU patients.Genetics in medicine open · 2026Article
- Toward a National Health Digital and Data Architecture: Laying the Foundation for Digital Transformation: Commission on Investment Imperatives for a Healthy Nation.NAM perspectives · 2026Review
- Uncovering the Molecular Signatures of Rare Genetic Diseases in the Punjabi Population.International journal of molecular sciences · 2025Observational
- Genetic disorders and associated morbidity, mortality, and congenital anomalies in preterm infants born at less than 34 weeks of gestation.BMC pediatrics · 2025Observational
- Integrating the Continuum of Genetic Testing From Fetus to Neonate: A Review of Prenatal Genetic Testing and the Overlap With Newborn Testing.Prenatal diagnosis · 2025Review
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
61 authors at 8 institutions in 3 countries.
Funding
Abstract
By informing timely targeted treatments, rapid whole-genome sequencing can improve the outcomes of seriously ill children with genetic diseases, particularly infants in neonatal and pediatric intensive care units (ICUs). The need for highly qualified professionals to decipher results, however, precludes widespread implementation. We describe a platform for population-scale, provisional diagnosis of genetic diseases with automated phenotyping and interpretation. Genome sequencing was expedited by bead-based genome library preparation directly from blood samples and sequencing of paired 100-nt reads in 15.5 hours. Clinical natural language processing (CNLP) automatically extracted children's deep phenomes from electronic health records with 80% precision and 93% recall. In 101 children with 105 genetic diseases, a mean of 4.3 CNLP-extracted phenotypic features matched the expected phenotypic features of those diseases, compared with a match of 0.9 phenotypic features used in manual interpretation. We automated provisional diagnosis by combining the ranking of the similarity of a patient's CNLP phenome with respect to the expected phenotypic features of all genetic diseases, together with the ranking of the pathogenicity of all of the patient's genomic variants. Automated, retrospective diagnoses concurred well with expert manual interpretation (97% recall and 99% precision in 95 children with 97 genetic diseases). Prospectively, our platform correctly diagnosed three of seven seriously ill ICU infants (100% precision and recall) with a mean time saving of 22:19 hours. In each case, the diagnosis affected treatment. Genome sequencing with automated phenotyping and interpretation in a median of 20:10 hours may increase adoption in ICUs and, thereby, timely implementation of precise treatments.
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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.