DNA Sequencers, Solving Diagnostic Mystery

DNA sequencing will be driven by killer applications, not by killer technologies.

DNA sequencing has started making huge strides in our current understanding of mechanisms of various chronic illnesses like cancers, metabolic disorders, inherited disorders, neurodegenerative anomalies, and transplant immunology. Latest trends in biomedical research are giving birth to a new branch in medicine referred to as precision medicine or personalized therapy. Technology has continuously evolved from Sanger to high-throughput next-generation and further to third-generation long read sequencers. This will reorient medical practice more toward disease prediction and prevention approaches rather than curing them at later stages of their development and progression. With the latest ability of long read DNA sequencers to capture all types of structural variations in genomes, it is easy to detect causal structural variations in a rare disease that include deletions, duplications, and other structural rearrangements, as well as a highly homologous pseudo gene.

Increased throughput read length and decreased running cost of current next-gen DNA sequencers creates opportunity to obtain high-quality, ethnicity specific medical grade genomes that better represent haplotypes common in their regional populations, thereby accelerating the use of precision medicine. For example, Craig Ventor genome, the first Human Genome reference completed in 2003, has been re-sequenced using latest long read DNA sequences. This allowed identifying unique variations on chromosome 20 alone, which include 196 novel insertions and 260 novel deletions with an average size of 634bp.

India is aggressively gearing up to adopt this current trend and many startups are joining hands to provide clinical diagnosis/prognosis utilizing DNA sequencers. Also, there is huge push for HLA donor registries to provide that most compatible match and this is only possible due to the ability of long read DNA sequencers to provide full length high-resolution allele level typing results and process large sample volumes.

Fueled by these technological advancements, precision medicine will use this knowledge to redefine diseases with new therapies and provide hope for generations of patients to come.

Global market

The global DNA sequencing market is anticipated to grow from USD 7898 million in 2017 to USD 34,087 million by 2026, at a CAGR of 17.64 percent between 2018 and 2026.

One of the major drivers for this market is the all-inclusive cost structure of sequencing products. Manufacturers developed an all-inclusive cost approach that includes the cost of components, direct costs, and indirect costs. This all-inclusive cost structure explains the cost structure to end-users and funding agencies. This cost approach reduces the volume of sequencing and increase the volume of data. Detailed cost-related data decreases the cost of sequencing and that increases the amount of genome data for better research. Consequently, detailed cost structure is driving the demand for DNA sequencing in the next-generation sequencing market. Increasing prevalence of cancer cases is another major driver boosting the global DNA sequencing market. A genomic period of cancer studies is advancing forward at a rapid pace, propelled by the advent of next-generation sequencing techniques that offer sharp resolution and sensitivity. Standardization and accurateness concerns in diagnostic testing and a dearth of skilled professionals are the major factors hindering the DNA sequencing market.

Technology trends

The evolution of DNA sequencing from nascent protocols to today’s high-throughput technologies has occurred at a breathtaking pace. Nearly 30 years of exponential growth in data generation have given way, in the past decade, to super-exponential growth. And the resultant data have spawned transformative applications in basic biology and beyond – from archaeology and criminal investigation to prenatal diagnostics.

What will the next 40 years bring?

Prognosticators are typically wrong about which technologies – or, more importantly, which applications – will be the most disruptive. In the early days of the internet, few predicted that e-mail would achieve staggering popularity. Similarly, traders on Wall Street and investors in Silicon Valley failed to foresee that games, online video streaming, and social media would come to dominate the use of today’s available processing power and network bandwidth.

It would probably fare no better in predicting the future of DNA sequencing. So instead, a recent study offers a framework for thinking about it. The central message is that trends in DNA sequencing will be driven by killer applications, not by killer technologies.

In demand. Improvements in a technology can either increase or decrease demand. DNA sequencing will follow the pattern of computing and photography, not of tyres. As it becomes cheaper and more convenient, applications will proliferate, and demand will rise. As DNA sequencing breaks out of the research market and into clinical, consumer, and other domains, the rule of more supply means more demand will hold ever more strongly.

What is more, much of the basic science needed to interpret the data is already in place for a growing repertoire of practical applications (such as high-quality reference sequences of bacterial genomes, or the rules by which certain gene networks operate in healthy people). These range from recognizing microbial DNA sequences in unbiased surveys of environmental or clinical samples to identifying genome changes associated with known biological consequences.

Killer applications. Over the years, the platforms for DNA sequencing have changed dramatically. Yet the trajectories of other technologies for which there is a seemingly insatiable demand – smartphones, the internet, digital photography – suggest that the real disrupters will be the resulting applications, not the new technologies.

Various applications can be envisioned outside the clinic, too, particularly for hand-held DNA sequencers. Epidemiologists and even caregivers working in rural areas could use such devices to test air, water, food, and animal and insect vectors, not to mention human throat swabs and body fluids. In fact, easy access to DNA-sequencing technologies in low- and middle-income countries is already facilitating projects such as the Global Virome Project. This aims to sequence numerous samples of wildlife DNA to identify a significant fraction of the viruses that can be transmitted into humans and cause disease.

Meanwhile, public-health specialists are starting to discuss how they might sequence the DNA of all the microorganisms in the waste-water outlets of entire cities to speed up the recognition of disease outbreaks. And marine biologists are exploring ways to monitor the health of the oceans through systematic metagenomic studies.

On the street, portable instruments could bring DNA analysis out of the crime lab and make it a front-line policing tool. Police might be able to read people’s DNA, much as they currently check car number plates or identification documents. In fact, the degree to which cheap and easy DNA sequencing opens up possibilities for mass surveillance has recently sparked concern among human-rights groups.

In the home, DNA-sequencing appliances could become the next smart or connected devices, after smoke alarms and thermostats. One commentator even identified the toilet as the ideal place to monitor family health through real-time DNA sequencing.

Hitting limits. What are the stumbling blocks? In a mere 40 years, the central goal of putting molecular data about cells to practical use has changed from an informational challenge to a meta-informational one. Take clinical applications of genome-sequence data. It may soon be possible to use DNA sequencing routinely to analyze body fluids obtained for any clinical purpose. But only a vast amount of well-organized data about the multi-year medical histories of millions of people will provide the meta-information needed to establish when to ignore such data and when to act on them.

Way forward

Surprises are a certainty. In fact, it is possible that decades from now, much of the world’s data (now residing on hard drives or in the cloud) will be stored in DNA, and that the main driver of DNA sequencing will be not our quest to tackle disease, but an insatiable appetite for data storage.