A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases

The American Journal of Human Genetics, Journal Year: 2022, Volume and Issue: 109(9), P. 1605 - 1619

Published: Aug. 24, 2022

Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive it concomitantly examines almost all diseases and gaining acceptance disease diagnosis ill newborns. We describe prototypic methods scalable, parentally consented, feedback-informed of rWGS virtual, acute management guidance (NBS-rWGS). Using established criteria the Delphi method, we reviewed 457 NBS-rWGS, retaining 388 (85%) with effective treatments. Simulated NBS-rWGS 454,707 UK Biobank subjects 29,865 pathogenic or likely variants associated had a true negative rate (specificity) 99.7% following root cause analysis. 2,208 critically children suspected 2,168 their parents, simulated identified 104 (87%) 119 diagnoses previously made 15 findings not reported (NBS-rWGS predictive value 99.6%, positive [sensitivity] 88.8%). Retrospective diagnosed that been undetected conventional NBS. 43 children, NBS-rWGS-based interventions started on day life 5, consensus was symptoms could have avoided completely seven mostly 21, partially 13. invite groups worldwide to refine these conditions join us prospectively examine clinical utility cost effectiveness.

Language: Английский

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Artificial intelligence and machine learning in precision medicine: A paradigm shift in big data analysis

Progress in molecular biology and translational science, Journal Year: 2022, Volume and Issue: unknown, P. 57 - 100

Published: Jan. 1, 2022

Language: Английский

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Artificial Intelligence in Molecular Medicine

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(26), P. 2456 - 2465

Published: June 28, 2023

Machine-learning methods for analyzing genomic, transcriptomic, epigenomic, proteomic, and metabolomic data sets have yielded clinically directive information, mostly rare genetic diseases.

Language: Английский

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Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association

Circulation, Journal Year: 2024, Volume and Issue: 149(14)

Published: Feb. 28, 2024

A major focus of academia, industry, and global governmental agencies is to develop apply artificial intelligence other advanced analytical tools transform health care delivery. The American Heart Association supports the creation services that would further science practice precision medicine by enabling more precise approaches cardiovascular stroke research, prevention, individuals populations. Nevertheless, several challenges exist, few have been shown improve sufficiently be widely adopted. This scientific statement outlines current state art on use algorithms data in diagnosis, classification, treatment disease. It also sets out advance this mission, focusing how digital and, particular, may provide clinical mechanistic insights, address bias studies, facilitate education implementation outcomes. Last, a key objective field identifying best practices, gaps, for interested stakeholders.

Language: Английский

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Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review

npj Genomic Medicine, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 27, 2024

Abstract Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid (URGS), rapid exome (RES) diagnostic tests for genetic ICU patients. In 44 studies children in ICUs with unknown etiology, 37% received diagnosis, 26% had consequent changes management, net costs were reduced by $14,265 per child tested URGS, RGS, or RES. URGS outperformed RGS RES faster time to higher rate diagnosis clinical utility. Diagnostic outcomes will improve as methods evolve, decrease, testing is implemented within precision medicine delivery systems attuned needs. currently performed <5% the ~200,000 likely benefit annually due lack payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition possible diseases, current formatting rather than system. The gap between actual optimal increasing since expanded use lags growth those through new therapies. There sufficient evidence conclude that should be considered all uncertain etiology at admission. Minimally, ordered early during admissions critically ill infants suspected diseases.

Language: Английский

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Artificial intelligence in clinical genetics

European Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Artificial intelligence (AI) has been growing more powerful and accessible, will increasingly impact many areas, including virtually all aspects of medicine biomedical research. This review focuses on previous, current, especially emerging applications AI in clinical genetics. Topics covered include a brief explanation different general categories AI, machine learning, deep generative AI. After introductory explanations examples, the discusses genetics three main categories: diagnostics; management therapeutics; support. The concludes with short, medium, long-term predictions about ways that may affect field Overall, while precise speed at which continue to change is unclear, as are overall ramifications for patients, families, clinicians, researchers, others, it likely result dramatic evolution It be important those involved prepare accordingly order minimize risks maximize benefits related use field.

Language: Английский

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An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 26, 2022

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians lack familiarity with these diseases, timely molecular diagnosis may improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for disease and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, superior analytic performance structural copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, evidence-of-efficacy of 9911 drug, device, dietary, surgical interventions 563 severe, childhood, diseases. The 421 (75%) 1527 (15%) retained integrated 13 information resources appended diagnostic reports ( https://gtrx.radygenomiclab.com ). This provided correct diagnoses four retrospectively two prospectively tested infants. Genome-to-Treatment facilitates optimal outcomes children progressive

Language: Английский

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Newborn Screening by Genomic Sequencing: Opportunities and Challenges

International Journal of Neonatal Screening, Journal Year: 2022, Volume and Issue: 8(3), P. 40 - 40

Published: July 15, 2022

Newborn screening for treatable disorders is one of the great public health success stories twentieth century worldwide. This commentary examines potential use a new technology, next generation sequencing, in newborn through lens Wilson and Jungner criteria. Each ten criteria are examined to show how they might be applied by programmes using genomic sequencing as tool. While there obvious advantages method that can examine all disease-causing genes single assay at an ever-diminishing cost, implementation scale presents numerous challenges, some which intrinsic rare disease specifically linked genomics-led screening. In addition questions specific routine considerations, ethical, communication, data management, legal, social implications require consideration.

Language: Английский

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The Role of Genome Sequencing in Neonatal Intensive Care Units

Annual Review of Genomics and Human Genetics, Journal Year: 2022, Volume and Issue: 23(1), P. 427 - 448

Published: June 9, 2022

Genetic diseases disrupt the functionality of an infant's genome during fetal-neonatal adaptation and represent a leading cause neonatal infant mortality in United States. Due to disease acuity, gene locus allelic heterogeneity, overlapping diverse clinical phenotypes, diagnostic sequencing intensive care units has required development methods shorten turnaround times improve genomic interpretation. From 2012 2021, 31 studies documented utility first-tier rapid or ultrarapid whole-genome through cost-effective identification pathogenic variants that change medical management, suggest new therapeutic strategies, refine prognoses. Genomic diagnosis also permits prediction reproductive recurrence risk for parents surviving probands. Using implementation science quality improvement, deployment learning healthcare system will contribute reduction integration into best-practice care.

Language: Английский

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Applications of artificial intelligence in clinical laboratory genomics

American Journal of Medical Genetics Part C Seminars in Medical Genetics, Journal Year: 2023, Volume and Issue: 193(3)

Published: July 28, 2023

Abstract The transition from analog to digital technologies in clinical laboratory genomics is ushering an era of “big data” ways that will exceed human capacity rapidly and reproducibly analyze those data using conventional approaches. Accurately evaluating complex molecular facilitate timely diagnosis management genomic disorders require supportive artificial intelligence methods. These are already being introduced into identify variants DNA sequencing data, predict the effects on protein structure function inform interpretation pathogenicity, link phenotype ontologies genetic identified through exome or genome help clinicians reach diagnostic answers faster, correlate with tumor staging treatment approaches, utilize natural language processing critical published medical literature during analysis use interactive chatbots individuals who qualify for testing provide pre‐test post‐test education. With careful ethical development validation genomics, these advances expected significantly enhance abilities geneticists translate clearly synthesized information managing care their patients at scale.

Language: Английский

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