Rady Children's Institute for Genomic Medicine, San Diego, CA, 92123, USA.
Rady Children's Hospital, San Diego, CA, 92123, USA.
Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6.
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.
虽然许多遗传性疾病都有有效的治疗方法，但如果不立即实施这些治疗方法，这些疾病常常会迅速发展为严重的发病率或死亡率。由于一线医生通常不熟悉这些疾病，因此及时的分子诊断可能并不能改善预后。在此，我们介绍了 Genome-to-Treatment，这是一种用于遗传疾病诊断和急性管理指导的自动化虚拟系统。通过加速全基因组测序，在 13.5 小时内即可完成诊断，在结构和拷贝数变异方面具有卓越的分析性能。一个专家小组对 563 种严重的儿童遗传性疾病的 9911 种药物、设备、饮食和手术干预的适应证、禁忌证、疗效和疗效证据进行了裁决。保留了 421 种（75%）疾病和 1527 种（15%）有效干预措施，并与 13 种遗传疾病信息资源集成，并附加到诊断报告中（https://gtrx.radygenomiclab.com）。该系统在四个回顾性和两个前瞻性测试的婴儿中提供了正确的诊断。Genome-to-Treatment 系统有助于患有快速进展性遗传性疾病的儿童获得最佳结果。
