Erratum: Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene,

[This corrects the article DOI: 10.1038/npjgenmed.2015.7.]

Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene,

An important component of precision medicine-the use of whole-genome sequencing (WGS) to guide lifelong healthcare-is electronic decision support to inform drug choice and dosing. To achieve this, automated identification of genetic variation in genes involved in drug absorption, distribution, metabolism, excretion and response (ADMER) is required

Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to$7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients

Additional file 1: Figure S1. of A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases

Screen-shots demonstrating the functionality of SSAGA. A. The clinical feature entry page. Synonyms for each feature are entered in the top left box. Upon entry, a list of matching HPO terms is displayed. The appropriate HPO term is selected and added to the patient’s feature list in the box on the right. This is performed for each clinical feature. In this case, patient CMH672ref, the patient had 11 clinical features that included neonatal seizures and a characteristic facies. B. Upon clicking the ‘Get Diagnosis’ button, the list of all matching diseases is generated. In this case, the differential diagnosis had 1,136 rows, representing 597 genes, of which 222 matched two or more clinical features. (PDF 240 kb

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19 septembre 18791879/09/19 (A13,N4882)