Mike Friez takes to the treadmill to Race the Helix at the Festival of Genomics

We’ve all been told that next generation sequencing is revolutionising healthcare. But how is it actually being applied, today? Read on to find out how sequencing data is turned into actionable, informed patient diagnoses and treatment.

When not Racing the Helix with the rest of the Greenwood Genetic Center family, Michael Friez heads up the Diagnostic Laboratory at the genetic nirvana. Read the full article in the latest issue of FLG Magazine.

Next Generation Sequencing (NGS) has certainly made life for geneticists (as well as their friends and colleagues) more interesting…and challenging. Most molecular diagnostic laboratories that offer sequencing tests for clinical conditions are spending the majority of their time these days focused on multigene panels, exomes and genomes. Technically speaking, NGS is the methodological platform that encompasses several capabilities which include targeted capture of selected genomic regions, massively parallel sequencing of these regions along with bioinformatic solutions to identify genomic variants or patterns that may be biologically relevant. This spectacular technological advancement provides volumes of data the likes of which the genomics community has never before seen. It is commonly utilised for addressing many medically significant issues, including the clinical evaluation of individuals believed to have a disorder of genetic origin.

Want to find out more about NGS in clinical services? Check out our brand new 101 guide to Clinical Genomics

Single gene tests performed using traditional Sanger sequencing still have a prominent role in the clinical world, but most labs don’t appear overly interested in continuing their test development efforts in this direction. This decision comes with good reason given the capabilities that NGS has enabled. It may also be in part due to the notion that the most commonly diagnosed Mendelian conditions and their associated confirmatory gene tests have sufficient availability. Add to the mix the confounding factors of genetic heterogeneity, reduced penetrance and variable expressivity, it’s no wonder that NGS-based tests have become a routine testing option for many clinical teams that work tirelessly to provide answers to the unknown.

Prior to life with NGS, clinicians were required to systematically prioritise sequential single-gene tests, in hopes of identifying the underlying genetic cause for their patients. This traditional testing strategy was often cost-prohibitive, time-consuming and excessively inefficient. NGS overcomes most of the hurdles of traditional single-gene testing, and often leads to a finding that ends the “diagnostic odyssey” for many families.

NGS applications aimed at detecting pathogenic alterations come in three general and overly-simplified categories: Targeted/ Focused panels (small), Whole Exome (medium) and Whole Genome (large). Most agree that Whole Genome Sequencing (WGS) will ultimately become the gold-standard in time as NGS methods, particularly on the data management side, are continuously improved. That being said, there continues to be a great deal of discussion regarding the current clinical utility and future of Targeted panels and Whole Exome Sequencing (WES). WGS and WES offer what has been referred to as “non-hypothesis driven testing” as these NGS options offer incredible opportunities to “find the genetic needle in the haystack”. They also come with the challenge of detecting significantly more variants that are often near impossible to fully understand or interpret from a clinical perspective. Some may take issue with the preceding statement, but for those familiar with the term “Variant of Unknown Significance” (VUS) it rings very true. So with all due respect to the genomic power of WGS and other NGS applications (known and unknown) the remainder of this brief communication will focus on Targeted panels. These remain the most clinically requested of the categories given their clinical utility, the logistics involved, and the cost to consumers.