Forging Ahead to New Heights

With the advancements in the technologies to detect the DNA sequence, from the foundational approaches such as Maxam & Gilbert’s and Sanger sequencing, the domain of DNA sequencers has rapidly evolved in capacity, capability, cost, and applications. The revelations about the enormous complexity of genome architecture have brought these sequencing technologies to even greater advancements. The next-generation methods massively parallelize the sequencing of relatively short fragments of DNA, achieving much higher throughput. Since then these technical advents have paved the way for increasing automation, opening the world to an era of next generation sequencing methodologies.New market players are envisioned to get attracted to the market as technological innovations take precedence. Established players can expect to leverage new opportunities in the market with sophisticated technologies such as chain terminator DNA sequencing and next generation DNA sequencing.

Vendors can also find lucrative opportunities in the clinical field as the DNA sequencer is highly demanded in numerous clinical applications. Next-generation DNA sequencers, particularly, are receiving high attention with the providence of novel platforms from the ongoing quantum leaps in microfluidics, bioinformatics, nanotechnology, and imaging. Such breakthroughs are also predicted to revolutionize a number of life science fields, thus providing an easy path of growth for the market.

Global Market
The global DNA sequencing instruments, reagents, and consumables market is projected to reach USD 4.6 billion by 2020 from USD 3.1 billion in 2016, at a compound annual growth rate (CAGR) of  9.5 percent.

The worldwide market for sequencing products is forecast to grow at a 5-year compound annual growth rate (CAGR) of 18.7 percent to reach nearly USD 13.8 billion by 2020, estimates BCC Research. The services segment had secured a colossal share in 2016 while instruments and consumables was one of the most rapidly growing segments in the same year.

Emerging sequencing systems, single molecular or nanopore sequencing, are still in an early market stage, with platforms only recently introduced. These new sequencing technologies promise to fill new market niches that are presently underserved by the main sequencing technologies.

Since its commercial introduction more than a decade ago, next-generation sequencing (NGS) has matured into an essential life science tool for genetic studies in a range of applications. The NGS industry is on the cusp of a second growth phase, powered by new market applications such as clinical and consumer sequencing.

Sequencing services is the fastest-growing segment, with an anticipated 5-year CAGR of 26 percent. The value of the sequencing services segment is forecast to exceed USD 9 billion by 2020. The high growth rate is due to a number of factors, including the expansion of sequencing into new applications in the clinical and applied market segments.

The main clinical applications driving market growth are cancer and reproductive health. In cancer, there is a growing need for genomic profiling tests that can be used as the basis for treatment decisions. This is part of a general trend for characterizing cancer on a genomics, rather than anatomic, basis. Also, the maturation of large-scale government research initiatives like the Cancer Genome Atlas should spur growth in this market. These projects help to uncover the underlying genomic basis for cancer, creating a need for sequencing diagnostics to help evaluate, treat, and monitor cancer cases.

Non-invasive prenatal diagnostics (NIPT), for high-risk women, should drive growth in the reproductive health application. In-vitro fertilization, carrier screening, newborn screening, and NIPT for average-risk women are anticipated as key drivers, as well.

Technological Advances
Technology is quickly moving from the lab into hospitals, clinics, and even homes with the advent of consumer genomics. Companies are looking for new ways to capitalize on the growing clinical and consumer markets with new applications, and become an essential part of every aspect of the DNA ecosystem.

Long-read technology. Both the real-time and synthetic long-read technology have gained importance in the recent past in addition to the short-read technology that was already in use. While the real-time technology harnesses the natural processes of DNA replication and ensures real-time observation of DNA synthesis, synthetic long-read technology relies on a system of barcoding to associate fragments that are sequenced on existing short-read sequencers. This simplifies de novo sequencing since large repeat regions in the DNA fragments can easily be spanned and has paved a way to the wide-scale, whole-genome sequencing in humans.

Single-cell genomics. With the advancements in technology and reduction in sequencing costs, the focus of studies has been shifted to individual cells from the mixture of cells to gain a window into cell-to-cell variation. This has been proven to be of utmost importance in the study of tumor biopsies and transcriptomics.

Real-time single molecule electronic DNA sequencing. A group of researchers from Columbia University, Harvard University, and the National Institute of Standards and Technology (NIST) have reported to achieve real-time single molecule electronic DNA sequencing at single-base resolution using a protein nanopore array. DNA sequences are obtained for many single molecules in parallel and in real time. This platform has the potential to produce a miniaturized DNA sequencer that is capable of deciphering the genome and thus facilitating personalized precision medicine.

Portable sequencers. The last year has been marked with the release of nanopore-based, handheld sequencers. These portable sequencers read long strands of DNA by measuring changes in electrical current as a nucleotide passes through a microscopic pore. With the capability to sequence long reads in real-time with low-cost inputs and the subsequent improvements in design and enzyme chemistry, these sequencers have secured a position in the market.

Optical nanopore sequencing. A DNA sequencing platform with the aim to create a standard for medical research that can sequence a complete human genome in minutes. This technology incorporates nanochannels to deliver single DNA molecules through nanopores. Dr Brueck, one of the team members explained the innovation, “Nanopore sequencing analyzes long DNA strings, with long reads that provide more accurate identification of genome variations. It is an approach, therefore, that leads to a more thorough, faster, and accurate genomic analysis, allowing researchers to substantially improve the ability to make new discoveries.”

Integrating software with sequencing. With a substantial increase in data generated, the storage, analysis and interpretation of that data remains a strenuous job. New ventures currently in development focus to incorporate software into the sequencing. This offers a cloud-based software tool, thus easing the storage, analysis and interpretation of DNA data.

Challenges
Although exciting, technological advancements are not without limitations. As new technologies emerge, existing problems are exacerbated and new problems arise. NGS platforms provide vast quantities of data, but the associated error rates (~0.1–15%) are higher and the read lengths generally shorter (35–700 bp for short-read approaches) than those of traditional Sanger sequencing platforms, requiring careful examination of the results, particularly for variant discovery and clinical applications. Although long-read sequencing overcomes the length limitation of other NGS approaches, it remains considerably more expensive and has lower throughput than other platforms, limiting the widespread adoption of this technology in favor of less-expensive approaches. Finally, NGS is also competing with alternative technologies that can carry out similar tasks, often at lower cost; it is not clear how these disparate approaches to genomics, medicine, and research will interact in the years to come

The Road Ahead
Next-generation sequencers with dynamism, high throughput, and scalability are reaching new heights to unveil new areas for researchers. With all the technological advents entering the market, the aim is to target a sequencing platform to reveal the complexities of genome, and ultimately, propel towards an era of personal genomics and personalized medicine. Next-generation sequencers have the ability to generate hundreds of gigabases of nucleotide sequence data in a single sequencing run imparting its usage in various clinical applications such as cancer, inherited genetic disorders, HLA typing, and identification of infectious diseases. Miniaturization of DNA sequencers and introduction of long-read, real-time DNA sequencing technology have proven to be crucial in deciphering the genomes.

The world is progressing toward digital DNA data storage, which will further escalate the demand for DNA sequencers and tools to store and analyze the high throughput data. These NGS tools have the potential to revolutionize modern science by allowing direct sequencing of RNA or proteins, real-time genomic pathogen monitoring or precision medicine based on personal genome sequencing and thereby, holding a promising future for the healthcare industry.