Abstract
BackgroundVariant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually searching through a multitude of independent databases, often with the aid of several, mostly independent, computational tools. To streamline variant interpretation, we developed the GeneTerpret platform which collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in the genome(s). The platform assigns quantitative validity scores to genes by query and assembly of the genotype–phenotype data, sequence homology, molecular interactions, expression data, and animal models. It also uses the American College of Medical Genetics and Genomics (ACMG) criteria to categorize variants into five tiers of pathogenicity. The final output is a prioritized list of potentially causal variants/genes.ResultsWe tested GeneTerpret by comparing its performance to expert-curated genes (ClinGen’s gene-validity database) and variant pathogenicity reports (DECIPHER database). Output from GeneTerpret was 97.2% and 83.5% concordant with the expert-curated sources, respectively. Additionally, similar concordance was observed when GeneTerpret’s performance was compared with our internal expert-interpreted clinical datasets.ConclusionsGeneTerpret is a flexible platform designed to streamline the genome interpretation process, through a unique interface, with improved ease, speed and accuracy. This modular and customizable system allows the user to tailor the component-programs in the analysis process to their preference. GeneTerpret is available online at https://geneterpret.com.
Highlights
Variant interpretation is the main bottleneck in medical genomic sequencing efforts
In an effort to facilitate genome interpretation by presenting a unified all-in-one platform for the average genome analyst, we have developed GeneTerpret, a customizable Genomic Variant Interpretation (GVI) platform, and visual analytics tool that accelerates the prioritization of genomic variants with an easy interface for expert interaction
We developed the GeneTerpret platform as a bioinformatics tool to facilitate the process of identifying diseasecausing variants
Summary
Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually searching through a multitude of independent databases, often with the aid of several, mostly independent, computational tools. The platform assigns quantitative validity scores to genes by query and assembly of the genotype–phenotype data, sequence homology, molecular interactions, expression data, and animal models It uses the American College of Medical Genetics and Genomics (ACMG) criteria to categorize variants into five tiers of pathogenicity. Several independent computer programs are available to aid GVI, the process routinely requires manual interpretation by a human analyst who leverages expertise, insight and phenotypic knowledge to curate a list of candidate variants. This process is often tedious, repetitive, time-consuming, and may be prone to human errors. A unifying platform for GVI is needed to help standardise the process and outcomes
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