GenePeeks’ unique, patent-protected platform enables the rapid and accurate analysis of clinically relevant genotypes and variants -- including the full spectrum of VUS’s -- to support a clinical workflow.
The interactive, web-based system facilitates access to multifactorial data informing the measurement of variant damage and genotype pathogenicity.
|Total variants||Pathogenic (ClinVar)||Pathogenic (GenePeeks)||Additional Coverage (GenePeeks)|
Variants observed in ExAC database using 4,791 genes in TruSight One panel, 2017.
|In detecting ClinVar pathogentic variants before they are added to ClinVar|
GenePeeks calls against ClinVar naive calls; Internal GenePeeks analysis, 2017.
GenePeeks’ platform generates standardized estimates of disease likelihood and severity by calculating a Variant Gene Dysfunction (VGD) score for all identified variants in the genome, including variants of unknown or uncertain significance (VUS).
The platform integrates data from multiple validated, peer-reviewed sources to compute the degree to which any variant, known or novel, reduces normal gene function. Variant attributes from these diverse set of resources are combined in a novel computational process to generate a single summary VGD score.
The platform scores every computed gene allele (with one or more variants) on a full 0 to 1 scale where a 0 has no effect on gene function and a 1 shuts down the gene. After computing these VGD scores, the system computationally generates gene-specific and genotype-specific output metrics.
For our preconception screen, these metrics are mapped to “virtual progeny” diploid genomes, but the same emphasis on genotype-specific analysis informs our post-natal diagnostic applications, currently in clinical development.
GenePeeks’ platform uniquely considers the combined effect of two chromosomal copies in a genotype. For every analyzed gene in a genotype, the system accumulates the disease risk quantified by VGD and evaluates the corresponding gene product’s functionality. Importantly, the platform calibrates the combined allele dysfunction relative to the scoring distribution of clinically validated variants within the same gene to account for differing levels of gene tolerance.
The assessment of genotypes enables a more comprehensive assessment of variant damage by: (1) quantifying the gene effects of variants, including variants of unknown significance and (2) integrating the total variant impact on gene function rather than examining variants in isolation.
The focus on genotype pathogenicity also enables a reduction in the number of candidate genes flagged for review, which significantly expedites the time involved in the assessment of disease and disease risk. In comparison to other interpretation platforms, GenePeeks offers a ~100x improvement in genotype curation time.
In the spirit of sharing information and advancing the progress and practice of human genetics, we created the publicly accessible GenePeeks Research Browser (GPRB). GPRB is an interactive web application intended for comprehensive variant, gene, and disease curation.
The centerpiece of GPRB are the novel graphic displays integrating population and clinical data with Variant Gene Dysfunction (VGD) scores. The graphs for ~5,000 genes currently analyzed by the GenePeeks platform can be searched through the GPRB search bar.View Browser