CENTOGENE develops a new validation framework to optimize the specificity and sensitivity of diagnostics based on Exome sequencing

CENTOGENE, a company specializing in rare diseases committed to improving the lives of patients with rare diseases by providing solutions to accelerate drug development, has published the development of a justification framework enabling to optimize the sensitivity and specificity of diagnostics based on whole exome sequencing (WES). population of clinically heterogeneous patients using orthogonal Sanger sequencing validation.

While next-generation sequencing (NGS) clearly replaces Sanger's DNA sequencing method not only for research but also for routine genetic diagnostic tests, studies have shown that it is not as reliable than the autonomous genetic test. Since NGS has introduced a relevant number of false positives and false negatives, CENTOGENE has determined how to optimize the use of parallel Sanger orthogonal sequencing of variants when one examines borderline cases. In the January 2019 issue of Genetics in Medicine, CENTOGENE describes in the manuscript titled "Development of an Evidence-Based Algorithm that Optimizes the Sensitivity and Specificity of ES-based Diagnosis in a Patient Population". clinically heterogeneous – a framework in which NGS variant calls can be evaluated consistently. and monitored, greatly reducing the burden of this additional validation.

CENTOGENE has developed a decision tree taking into account three characteristics specific to each variant: quality score, number of readings and frequency. Using this predictor, it is possible to clbadify 91.7% of the variants with a specificity of 100% and a sensitivity of 99.8%, leaving only 8.3% of the variants to be confirmed with an additional Sanger sequencing. This result avoids the results of excessive and insufficient filtering, thus generating a more accurate diagnosis for patients with rare diseases that would otherwise have been missed. The implications of this increased specificity and sensitivity also translate into more consistent surveillance capabilities.

The new framework we have developed to optimize the sensitivity and specificity of WES-based diagnostics underscores CENTOGENE's strategic focus on clinical and genetic data transformation to enable rapid medical diagnosis of hereditary diseases, said the Professor. Peter Bauer, MD, Scientific Director of CENTOGENE and lead author of the study. This framework can be optimized in the industry, academia and clinic without compromising the accuracy of the genetic diagnosis.

The study was conducted on a large population of real-world patients and integrates data from approximately 1,000 candidate genomic variants. Patient samples were provided as EDTA blood or dried blood spots on filter cards using CENTOGENE CentoCard ^{a global logistics solution developed by CENTOGENE to simplify the collection of samples all over the world.}

About CENTOGENE CENTOGENE is a rare disease company specializing in the transformation of clinical and genetic data into medical solutions for patients. We are focused on streamlining treatment decisions and accelerating the development of new orphan drugs using our knowledge of the global rare-disease market, including epidemiological and clinical heterogeneity and innovative biomarkers.

CENTOGENE, one of the world's leading rare disease societies, is dedicated to transforming the science of genetic information into solutions and hope for rare disease patients and their families. www.centogene.com.

CENTOGENE
Ross Bethell
Director, company
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