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Happy 2018!  2017 saw a renewed interest in copy number analysis particularly from NGS data and I think it's going to be a key topic in 2018. The ability to obtain copy number from the same assay as that used for SNVs is an important topic among genetics labs. Clinicians are now starting to realize the major benefits in consolidating tests to a single NGS assay analyzed on a single software system:

  • Cost savings by reducing the number of tests needed
    • E.g. cost analysis from Shen W, et al. J Clin Pathol 2017
    • $850 - Single assay for CNV, AOH, mutations
    • $1300 - Combined direct cost of SNP array ($650) and targeted NGS mutation panel ($650)
  • Time savings with the ability using a single test vs. a multi-tier approach that requires several tests in sequence
  • Ability to identify compound events (SNVs in regions of homozygosity) which can easily be missed when using separate technologies and software systems
  • Increased turnaround delivering a diagnosis to patients much more quickly

There have been many obstacles in attaining this single assay approach. One hurdle has been the ability to generate high quality copy number calls from sequencing data. But once that is achieved, the question turns to "what do we do with the results?" Often methods for estimating copy number from sequencing data are

  • new and not well-tested
  • apply only to select technology
  • are very specific to a lab’s workflow
  • don’t have a system for visualization which is key for CNVs
  • are hard to generalize and apply across different tests and technologies (WES, WGS, targeted panels, etc.) 

Another issue is that most software is designed to handle either one or the other (CNV or SNV) and each modality is utilized by separate groups that typically don't interact with each other. There is a need for the two branches to come together and a system uniting the two modalitites assists with this. 

BioDiscovery has been in the genomics software market for 20 years and our algorithms have been the gold standard in CNV calling for many years. We are currently on our 4th generation algorithm in a software that hundreds of labs globally have relied on for years. Our BAM MSR algorithm to derive copy number from sequencing data is now integrated in our clinical product (NxClinical). With the software’s robust algorithms, platform independence, strong visualization tools, and integrated analysis of CNV, Seq Var, and AOH, it is the system that can be easily adopted into a clinical setting for streamlining, speeding, and increasing diagnostic yield from a single NGS assay.

A recent paper in the European Journal of Medical Genetics evaluated the possibility of replacing CMA + sequencing with a single assay. The authors chose to use a commercial software, and selected BioDiscovery software, for reasons including

  • the ability to handle data from different technologies (microarray and NGS) - facilitates transition to use of NGS for CNV with validation of CNV from NGS by comparison to microarray results using the same algorithms and software
  • support for different NGS platforms (WES, WGS, targeted panels) - easy for a lab to use the platform that is best for a certain test
  • user-friendly interactive GUI (does not require command line programming) - allows geneticists with no programming knowledge to quickly learn and use the software
  • optimized for copy number estimation with rich visualization - very important to cytogeneticists

So with the start of the new year, as you plan out the year for your lab, take a look at the transitioning testing market and evaluate the benefits of a single assay approach for your organization.