Geographic distance to specialty centers correlates with time to diagnosis, receipt of specialty care, and outcomes in childhood genetic diseases 23, 24. Most healthcare providers lack adequate genomic literacy to practice genomic medicine, and depend upon other subspecialists, particularly medical geneticists, for translation of genome reports into treatment recommendations 19, 20, 21, 22. Clinical trials of rWGS have identified several factors that contribute to the gap between expected and observed clinical utility of genetic disease diagnoses: 3, 4, 7, 10 Firstly, exponential advances in genomics have outpaced medical education ( ). rWGS is now being implemented nationally for inpatient diagnosis of childhood genetic disease in England, Wales, Germany, in Medicaid beneficiaries in Michigan, California, Minnesota, and Oregon, and in Anthem/Blue Cross/Blue Shield beneficiaries nationwide ( ) ( ) ( ) ( ) ( ).Īs is often true in biotechnology, rWGS removed one bottleneck, but exposed another downstream-delayed, variable, or absent implementation of optimal, specific treatments. An initial, comprehensive technological solution to this problem was rapid diagnostic whole genome sequencing (rWGS), which enabled concomitant diagnostic evaluation of almost all genetic diseases in as little as 19.5 h 13, 14, 15, 16, 17, 18. In ICU settings, progression of childhood genetic diseases is often extremely rapid leading to morbidity and/or early death without a timely diagnosis and treatment 10, 11, 12. Of 140 million children worldwide suffering from rare genetic diseases, it is estimated ~30% will not survive to their fifth birthday 8, 9. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.Ĭollectively, the 7200 known genetic disorders engender a large proportion of pediatric morbidity and mortality, particularly in neonatal, pediatric, and cardiovascular ICUs 1, 2, 3, 4, 5, 6, 7. This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( ). An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases.
Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants.
Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately.
Nature Communications volume 13, Article number: 4057 ( 2022) An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases
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