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

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 frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. 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. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases. Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.

虽然许多遗传性疾病有有效的治疗方法，但如果不立即实施这些治疗，它们往往会迅速发展为严重的发病状态或导致死亡。由于一线医生往往对这些疾病缺乏了解，及时的分子诊断可能无法改善结果。在此我们描述了“基因组到治疗”（Genome - to - Treatment），这是一个用于遗传性疾病诊断和急性治疗指导的自动化虚拟系统。通过加速全基因组测序，可在13.5小时内完成诊断，对于结构变异和拷贝数变异具有优异的分析性能。一个专家小组对563种严重的儿童遗传性疾病的9911种药物、器械、饮食和手术干预措施的适应证、禁忌证、疗效和疗效证据进行了判定。保留的421种（75%）疾病和1527种（15%）有效干预措施与13种遗传性疾病信息资源整合，并附在诊断报告中（https://gtrx.radygenomiclab.com）。该系统对4例回顾性和2例前瞻性检测的婴儿做出了正确诊断。“基因组到治疗”系统有助于患有快速进展性遗传性疾病的儿童获得最佳治疗效果。 在许多遗传疾病中，快速诊断和实施治疗至关重要。在此作者描述了“基因组到治疗”，这是一个虚拟的疾病管理系统，它可以通过加速全基因组测序在13.5小时内实现快速诊断，并为临床医生提供可能的治疗指导。