Clinical analysis of genome next-generation sequencing data using the Omicia platform

Abstract

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance.

Succinyl-CoA synthetase ( SUCLA2 ) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion

“…The candidate SUCLA2 variants identified by VAAST were c.985A>G (p.Met329Val) and c.920C>T (p.Ala307Val) with Omicia scores of 0.94 and 0.79, respectively. The Omicia score represents a composite score using PolyPhen, MutationTaster, PhyloP and SIFT in silico prediction algorithms [24]. A score of ≥0.85 = 1% false-positive prediction rate [24].…”

“…The Omicia score represents a composite score using PolyPhen, MutationTaster, PhyloP and SIFT in silico prediction algorithms [24]. A score of ≥0.85 = 1% false-positive prediction rate [24]. Furthermore, a variant with an Omicia score of >0.85 is considered likely pathogenic, while one with a score between 0.5 and 0.85 is considered potentially pathogenic [24].…”

“…A score of ≥0.85 = 1% false-positive prediction rate [24]. Furthermore, a variant with an Omicia score of >0.85 is considered likely pathogenic, while one with a score between 0.5 and 0.85 is considered potentially pathogenic [24]. The reads for the candidate SUCLA2 variants were non-overlapping.…”

Settling the score: variant prioritization and Mendelian disease

“…Commercial tools increasingly have an important role in this domain, partly because of the complexity and cost of developing such software. Examples include Congenica’s Sapientia, WuXi’s NextCode, (see Further Information) and Fabric Genomics’ Opal platform 12 . These platforms offer customizable workflows and web-based user interfaces that facilitate expert review and interpretation of results.…”

“…The last several years have seen a proliferation of decision support frameworks for variant interpretation 12–15 . These interactive, often web-based, platforms are a big step forwards from simple command line-based analyses.…”