SAN FRANCISCO – Although it is still early days, next-generation sequencing (NGS) is being harnessed by researchers and clinicians to help them delve into the complexities of the molecular basis of diseases in order to reveal a patient's genomic profile and how that information relates to the causes of their conditions.

The powerful disruptive technology is churning out a tsunami of genetic sequence data, which need to be carefully interpreted and translated into clinically relevant and actionable information. And that is indeed starting to evolve in creative ways, according to an expert panel at the recent J.P. Morgan Healthcare Conference drawn together to discuss the practical applications and growing clinical utility of NGS that will enable personalized approaches to prevent and treat disease thanks to improved diagnostics, biomarkers and targeted therapeutics.

Referring to an analogy from a commentary from Genetics in Medicine, panelist Randy Scott, founder and CEO of Invitae Corp., said clinical genomics needs to evolve to the level that high-definition (HD) television has today. "What is really exciting about the field now is that we have reached the stage where Moore's Law is just beginning to deliver.

"Although we have a ways to go to arrive at HD clinical-grade genomics we are developing tools that will provide enough 'pixels' on a large number of genes that will improve the ability of clinicians to make informed treatment decisions."

The fact that we are early in that growth curve was one of the reasons panelist John Stuelpnagel, co-founder and chairman of 10X Genomics, told the audience that he hasn't had his own genome sequenced. Not because of the cost or worries about what the results might reveal, but in his view sequencing was not yet robust enough for many of the applications that they are interested in.

X-RAY

Nevertheless, "this is an incredible exciting space," said Chad Robins, CEO of Seattle-based Adaptive Biotechnologies Corp., which is leveraging NGS to profile T-cell and B-cell receptors. At the company, "we sequence your adaptive immune system that provides a unique 'X-ray' into the system."

Robins commented that he believed this is the largest application space, or content area, of NGS because the immune system is involved in almost every therapeutic area. "It allows us to measure how individual patients respond to different treatments."

"There is a great deal of excitement about sequencing in general, and we share in this enthusiasm," said George Yancopoulos, chief scientific officer, Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y. He noted that for many years his company's therapeutic efforts have been founded on an interest on genetics. "We believe we have been at the forefront of genetic approaches to both target discovery validation and therapeutics development. Next-generation sequencing has become a critical component in this process, and we have one of the largest ongoing sequencing initiatives in the industry."

Regeneron has established the Regeneron Genetics Center (RGC), a wholly owned subsidiary, which is a fully integrated genomics program that spans early gene discovery and functional genomics and facilitates drug development. The primary goal of the RGC is to improve patient outcomes by identifying novel drug targets, clinical indications for development programs and genomic biomarkers for pharmacogenomic applications. To date, the RGC has sequenced de-identified samples from more than 10,000 individuals, leveraging laboratory automation and an innovative approach to cloud computing to achieve high-quality throughput at a rate that exceeds 50,000 unique samples per year.

"We may be one of a handful of companies in the entire industry that has started human genetics programs that have resulted in approved therapeutics and many of the late-stage products we currently have in our pipeline," Yancopoulos said.

However, sequencing isn't the limiting step in drug discovery; it is the biology. The biggest problem is aligning the gene with human disease, Yancopoulos noted.

That was one of the reasons Regeneron established a major human genetics research collaboration with Geisinger Health System in January last year focused on studying the genetic determinants of disease. During the initial five-year collaboration term, Geisinger plans to collect samples from more than 100,000 consented patient volunteers, while Regeneron, through its RGC, will perform sequencing and genotyping to generate de-identified genomic data. The size and scope of the study are meant to allow great precision in identifying and validating the associations between genes and human disease. (See The world of NGS heats up in this issue.)

"Geisinger has a unique phenotypic database so when we sequence individuals from their database we can align the genomics data with their condition."

INTERNET OF GENOMICS

Scott noted that although we are not there yet, the "internet of genomics" is coming to heath care. That is one of the promises being offered by Foundation Medicine Inc., which is building a database in oncology. Someday we will have a complete genomic profile database on every tumor across every patient in an open source network that clinicians will be able to access.

On the regulatory and reimbursement front, Adaptive Biotechnologies' Robins said the payer community is still behind the curve as far as the benefits of NGS are concerned.

And 10X Genomics' Stuelpnagel noted that the market for genetic testing and NGS will develop rapidly over the next two to three years toward medical applications driven by consumer demand and lower costs per genetic test. You have to establish a competitive advantage in the value chain in this market. That is why 10X is focusing on delivering products that extract more information derived from sequencers.

If genetic testing and NGS are overregulated by the FDA there is a danger that those technologies will move offshore stifling innovation in the U.S, he noted.