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NGS: The Next Big Thing in the Clinical Market

Next-generation sequencer technology is opening up exciting new clinical applications across a variety of industries. Learn more from EASi expert Courtenay Vining.

Since the 00’s, Next Generation Sequencers (NGS) have been processing DNA for  research applications conducted around the world. With ongoing improvements to read length and library prep, NGS has exponentially increased the speed of sequencing and reduced the cost per base, reducing timelines and overall costs for researchers.

This means exponentially more output in a previously impractical field with limitless implications, faster and cheaper than ever before. The total impact of NGS - on industries such as pharmaceuticals, biotech, medicine, and even consumer products - is likely to be revolutionary.

And NGS applications are now being tested in the clinical market.

Companies in a variety of clinical sectors have been eager to participate, with movement to quickly develop a wide range of possible NGS clinical applications representing a gold rush of sorts.

Considerations relevant to the current state of play include:

Understanding the limitations of NGS

As easy as it is to be hopeful about the possible clinical applications of NGS, technical challenges, critical expertise and upfront costs still present considerable barriers to entry.

The initial technology cost of a third-generation sequencer could be as high as into the seven figure range.

The regulatory environment is also uncertain with the FDA reviewing significant changes to NGS testing including guidance to change the oversight from CMS to the FDA for diagnosis of germline diseases by NGS.

The work necessary to meet data validation standards can vary by application. Such concerns are relevant in different ways for the pharmacology industry, or for pharmacogenetics, oncology, therapeutics and bacteriology.

For those interested in exploring NGS applications there are still many challenges including method development, timeline to ROI, and whether to do it in house or outsourced.

As for clinical applications that are just starting to cross the necessary thresholds for method validation, we’re seeing the following:

Using NGS to validate patient sets

With regard to best practices for patient set validation, The Journal of Molecular Diagnostics published a joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists, titled “Guidelines for Validating NGS-Based Oncology Panels,” in May of 2017.

These guidelines operate primarily in the oncology space but can be modelled to other areas of diagnostics and pathology. Of particular note are the recommendations regarding minimal depth of coverage and sample number requirements, as well as an emphasis on error-based approaches to test design, methodology and quality assurance.

As for the current state of using NGS as a tool for patient set validation, it’s still in an experimental phase.

For instance, in the oncology space, people are just beginning to look at sequencing their patient base to determine whether outcomes are based on what’s happening with the drug rather than prior genetic disposition to the drug.

Using NGS for environmental monitoring

A research study titled “Next-generation sequencing technologies and their application to the study and control of bacterial infections” appeared in the April 2018 issue of Clinical Microbiology and Infection.

In it, authors Tassios and Moran-Gilad outline best practices and terminology for bacterial whole genome sequencing (WGS) to help environmental monitoring clinicians make sense of results and guide clinical practice.

Thanks to this work and other studies like it, the clinical space can now explore monitoring activity centered around organism identification in a variety of environments.

The chief benefit NGS brings to this space is the directness of the testing mechanism. Contaminants of a biological nature can now be identified in an unbiased way, using NGS sequencing processors to take samples, sequence everything and read directly what the organisms are at an individual level.

Complex disease state sequencing using NGS

NGS also has the potential to fundamentally alter our overall diagnostic and treatment approach to complex diseases by applying next-gen sequencing to the disease stage.

For example, a complex immunological disease like lupus, which is really a syndrome rather than a specific disease, can have all kinds of different causes. NGS can qualify a patient base and bin them based on genetic backgrounds, making it possible to attack each different symptom rather than lumping all disease sufferers together.

Such applications would advance our collective ability to develop clinical treatments that go after the actual root of the problem on an individual patient basis, rather than trying to unlock an overarching approach that broadly covers every disease presentation at once.

For further background on potential NGS applications for complex disease states, look at “Genetic diagnosis of autoinflammatory disease patients using clinical exome sequencing,” by Batlle-Masó, et al.

Navigating compliance for NGS

As promising as the potential clinical applications of NGS are, the fundamental impossibility of de-identifying gene sequences presents an enormously complex legal framework to negotiate. 

While the FDA has drafted language around regulations dealing specifically with clinical applications of sequencing, nothing has been accepted yet. One preliminary area of focus has been around surety levels for validation.

For further detail on the regulatory landscape, read “FDA guidance for next generation sequencing-based testing: balancing regulation and innovation in precision medicine” by Frank Luh and Yun Yen.

We can expect a regulatory framework to emerge and evolve along with the marketplace. In the meantime, the more conservative solution is the better solution.

Exploring the market for NGS services

Any of the above-mentioned applications can be accomplished through a developing market of sequencing service options. Firms looking to explore new NGS-based applications can choose their preference along a spectrum of external involvement.

Current options span anywhere from direct purchase and exclusive in-house lab use of an NGS, to partnership with a managed service provider for sequencing support, or intensively coordinated sample outsourcing to a large lab provider.

In the current state, specific requirements for NGS applications still vary on a case by case basis, due  to nuances between industries, regulations and experience level.

Want to learn more about NGS? Contact EASi now.