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Researchers awarded $4.8 million to validate locally developed test, EpiSign, for first-line diagnostic testing of rare hereditary disorders

Dr. Bekim Sadikovic

A clinical trial named “EpiSign-CAN,” led by researchers at Lawson Health Research Institute (Lawson) has been awarded $4.8 million to measure the clinical impact of a new molecular genomics test for diagnosing genetic neurodevelopmental conditions.

Developed at Lawson, the diagnostic test, called EpiSign, uses machine learning to analyze the EpiSign Knowledge Database. This database compiles information on rare genetic diseases using laboratory analyses of the entire genome, referred to as the epigenome, from patients with suspected genetic abnormalities.

A recent paper describes the newly discovered biomarkers for over 50 neurodevelopmental conditions. Dr. Bekim Sadikovic, Lawson Scientist and Head of the Molecular Diagnostics Division at London Health Sciences Centre (LHSC) explains, “before this study, many such conditions required targeted, and often labour intensive and costly assays for a diagnosis, which in many cases provided no conclusive answers. Now, using our EpiSign Knowledge Database which includes the epigenomic information of thousands of patients and controls, we are able to diagnose over 50 conditions with a single test, including in patients where targeted genetic testing was inconclusive.”

The upcoming clinical trial hopes to validate the use of this test in the first-line of diagnosing rare genetic disorders across Canada. “Patients and families typically wait years, and undergo multiple exams and lab tests in search of a definitive diagnosis. With EpiSign, we estimate that we will be able to increase the number of people who receive a diagnoses by five per cent, or more in the future as the database develops” explains Dr. Sadikovic. “Though individual genetic conditions are rare, there are over 4,000 recognized genetic disorders which affect thousands of patients in Canada.”

EpiSign-CAN will study 4,000 patients, who will either receive EpiSign testing as part of the initial diagnostic workup or after classical genetic testing approaches have been exhausted. The goal is to assess the impact of using EpiSign in the first stage of diagnosis vs. after other tests have failed to provide answers in this patient population.

Timely diagnosis will prevent the so called “diagnostic odyssey,” and by doing so has the potential to improve healthcare outcomes for these patients and decrease cost to the health system. 

As the EpiSign Knowledge Database continues to grow, researchers are finding correlations between specific episignatures, or molecular DNA markers, and related physiological features across a syndrome.

This research is co-funded through the collaboration of three partners; LHSC, Illumina, and Genome Canada. This is the first time researchers at Lawson have been awarded a Genome Canada Genomic Applications Partnership Program (GAPP) grant. “Genome Canada focuses its resources on new innovation that has a strong likelihood of translating directly to patient care. Their support of our work is extremely meaningful,” says Dr. Sadikovic.

The study describing the most recent advancements in EpiSign technology, “Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 Mendelian neurodevelopmental disorders,” is published in The American Journal of Human Genetics.