Ranomics Changing the Genetic Testing industry by Bringing Conclusive Interpretation Based on Functional Studies
It is no secret that the genetic testing industry is among one of the fastest changing industries over the past decade. Just 15 years ago, it cost over $100 Million to sequence the first human genome. Since then, the cost of genome sequencing has decreased faster than Moore’s Law. As we can see that in 2016, it costs less than $1000 to sequence an entire human genome. Genetic testing companies like Color Genomics and Veritas Genetics have made it their mission to democratize cancer prediction tests by lowering the average cost of a test 10-fold to $200-$300 USD. As genetic tests are becoming democratized, genomics is playing a greater role in our society and people are becoming increasingly aware of the wealth of knowledge held within each individual’s genome, for instance, through prenatal testing or hereditary disease prediction.
As technology advances, the main challenge in the genetic testing industry is no longer the cost of sequencing, but rather, the interpretation of the sequenced results, or what Bruce Korf, past president of the American College of Medical Genetics, calls “the $1-million interpretation.”
Traditionally, genetic variants are classified by clinical data. This means that clinicians assess the pathogenicity of a genetic variant based on family history and pedigree analysis.. However, only a small percentage of possible genetic mutations have been previously observed in sequenced patients, leaving the vast majority of genetic mutations unclassified. These mutations are termed variants of unknown significance (VUS) and since they cannot be interpreted using clinical data, patients with a VUS receive an inconclusive test result.
Inconclusive genetic tests result in emotional distress, anxiety, and a lack of appropriate diagnosis for patients who are expecting to make clinical decisions based on the test results. A recent lawsuit (url http://www.buzzfeed.com/stephaniemlee/dna-quest-lawsuit#.je8gq40d just for “lawsuit”) was filed toward genetic testing companies, Quest Diagnostics and Athena Diagnostics, for a “False DNA test” that was claimed to cause the death of a 2-year-old child. The lawsuit, which is pending in the U.S. District Court in South Carolina, accuses the companies for failing to report that the child had a genetic mutation linked with a rare seizure disorder that would have led to appropriate treatment which would have prevented the fatal incident. The root of this problem is caused by the genetic company’s incorrect interpretation on a variants of unknown significance (VUS) in the SCN1A gene. By Athena’s interpretation, this variant can affect normal gene activity but “often have no effect.”, and attorneys concluded that Athena should have interpreted this variant as a mutation that could cause disease. VUS affects patients every day, and this is merely one of many cases that an incorrect VUS interpretation making a large impact on the life of the patient.
At Ranomics, we believe that it is possible to solve this problem with lab-based experiments. We physically generate all possible variants of a disease gene, like the hereditary breast cancer gene BRCA1. We test the function of all variants in model organisms such as yeast and human cell lines. We then classify the harmfulness of each variant by measuring the functionality of each variant in the the model organism.
By classifying all possible variations of disease genes, we will be able to use this information to eliminate all variants of unknown significance (VUS) in genetic tests.
In addition to BRCA1, our goal is to apply our technology to 20–25 common hereditary cancer genes in the upcoming years. We want to change the way genetic results are analyzed by actively generating functional data for all possible variants before a variant is observed in patients. In a world where knowledge is power, we believe that the interpretation of sequenced human genomes will not only hold the key to our understanding of individual health and well-being, but also to empowering the next wave of personalized medicine.
