Two experts predict that tomorrow’s gene sequencing systems may render large swaths of today’s clinical laboratory obsolete

Gene sequencing is the hot technology in both the biotech and clinical laboratory testing industries. That is because the cost of rapid gene sequencing systems is falling rapidly, even as the speed and accuracy of these latest-generation gene sequencers improves significantly.

It is important that medical laboratories managers and pathologists understand the consequences of this technology development curve. The constantly-improving capabilities of these systems means that rapid gene sequencing and whole human genome sequencing will soon take their place in clinical laboratories and anatomic pathology groups.

Dark Daily is tracking this trend. At Scientia Advisors, experts Harry Glorikian, Founder and Managing Partner, and Brian Clancy, Associate, offered a heads up to the industry and investors, in an article in Genetic Engineering News. The authors addressed three trends:

1. sequencing activity polarization;
2. workflow value shifts; and,
3. clinical and commercial applications.

The information in the following paragraphs is based on that story.

Understanding Three Primary Trends in Rapid Gene Sequencing

Glorikian and Clancy say that the first trend, sequencing activity polarization, has to do with the conflicting forces that cause an increase in high-throughput sequencing activity to occur in both the largest and the smallest sequencing labs.

In recent years, the steady stream of technology innovations in gene sequencing have greatly improved the accuracy and the speed of automated gene sequencing systems, while greatly reducing the cost of sequencing a base pair. (image by coris.noaa.gov)

On one hand, the most important force driving the centralization of sequencing activity is the emergence of research consortia. These groups seek to sequence and analyze large numbers of human and other large genomes. Research consortia are driven by economies of scale. Thus, smaller laboratories may achieve lower costs and higher quality if they were to outsource their gene sequencing work to an emerging group of service providers.

On the other hand, the increasing availability of high-throughput gene sequencers that are affordable and fit on a desktop or workbench is one powerful—and much-discussed force that encourages decentralization of gene sequencing. Even more important are the less-discussed user needs that drive the broader demand for smaller, load-and-walk-away gene sequencing systems. Some examples of clinical applications for these smaller gene sequencing systems include panels of tests for oncology, genetic disease, and infectious diseases.

Workflow Changes Enabled by High-Throughput Gene Sequencing

Glorikan and Clancy define their second trend—workflow value shifts—as a period of more pronounced decommoditization and commoditization of resources used in the high-throughput sequencing workflow that go beyond the sequencing instrumentation and consumables themselves. Key drivers of this trend have to do with the maturation of second and later- generation sequencer technology. These factors are primarily technical in nature.

The authors observe that technical improvements to second-generation gene sequencers directly contribute to the de-commoditization of other instruments, consumables, software, IT infrastructure, and expertise used in the overall gene sequencing workflow.

The effects of this trend can be seen in the noteworthy shift that is occurring in the allocation of spending on gene sequencing components. Major genome centers have shifted their spending allocation on tools (instruments and consumables) from about 65% in 2005, to between 40% and 50% in 2010.

Glorikian and Clancy expect increasing investment emphasis on IT/informatics infrastructure, sample logistics infrastructure, and additional personnel (such as, bioinformatists and pathologists) to drive further decreases in the portion of genome center budgets that is allocated to tools.

• By contrast, spending for tools is expected to pick up over the next few years in these areas of sample-preparation instrumentation and consumables:
• DNA shearing
• Size-selection instrumentation and consumables
• Bisulfite sequencing kits
• Chromatin immunoprecipitation (ChIP) kits
• Sequence-enrichment instruments and consumables
• Bioinformatics tools

In the long term, third- and later-generation sequencing technologies could potentially render swaths of today’s clinical laboratory workflow obsolete. The reason is that single-molecule, real-time (SM/RT) technologies are expected make it unnecessary to amplify the DNA.

Gene Sequencing—Omnipotent Technology of the Future Medical Lab

Glorikian and Clancy define the third significant trend to be the diffusion of sequencing technology into clinical and commercial applications. Increasing demand for higher-performance sequencing systems and the rapid expansion of the technical performance envelope are two major forces pushing sequencing technology out of the research environment and into clinical diagnostics.

In the view of these two experts, this evolution of customer needs is more important than the gene sequencing technology’s performance-improvement trajectory. From an analytical perspective, what will increase demand from customers is a decrease in false negatives and false positives. From a clinical perspective, it is the desire to increase positive and negative predictive value.

The gene sequencing performance values of most interest to clinical and commercial customers include:

• how many markers are measured in a given test;
• the ability to detect mutated cells in a background of wild type; and,
• the ability to count the number of times a particular analyte is present.

For example, the authors believe that demand for the unique technical capabilities of high-throughput gene sequencing technology will be created in clinical contexts concurrent with at least two developments: 1) as more genetic markers are discovered, and, 2) as the clinical community becomes more interested in the relative abundance of important genetic mutations.

Glorikian and Clancy estimate that at least 20% of this application area will migrate to high-throughput gene sequencing platforms by about 2014, with accelerating penetration thereafter. Further, they predict that, between 2014 and 2020, there will be a multibillion dollar opportunity for gene sequencing technology and associated services devoted to a genome-first cancer-care paradigm.

These two experts were also willing to speculate that ongoing developments in rapid gene sequencing have the potential to upset the existing global market for in vitro diagnostics (IVD). They note that the regulated, commercial IVD market represents about $41 billion in annual sales.

Glorikian and Clancy wrote that, if a few racks of gene sequencing instrumentation can replace an entire clinical lab worth of clinical chemistry, immunoassays, microbiology, and molecular diagnostics equipment, then the current market shares of the world’s IVD industry heavyweights could ultimately be at risk.

Of course, the rate at which next-generation gene sequencing applications are adopted for clinical diagnostics applications that supplant or replace existing medical laboratory testing methodologies remains to be seen. However, because gene sequencing technology is improving at such a remarkable pace, savvy pathologists and clinical laboratory managers will want to stay informed about these new capabilities and how they can be used for clinical diagnostic purposes.

—Pamela Scherer McLeod

Related Information:

Sequencing Trends Worth Watching

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