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DNA Sequencers

DNA Sequencing Commemorates its 40th Anniversary

As DNA sequencing commemorates its 40th anniversary, advancements are being made toward third-generation sequencing tools with an ultimate goal of achieving precise real-time products.

In the past, the method of sequencing DNA was not only time-consuming and laborious but also greatly expensive. Moreover, at that time, it was possible only to sequence a small number of base pairs, which was too less from the number required to sequence a single gene. Fortunately, vast technological advancements have been made since then. Moreover, automation has made the process much faster, efficient, effective, and practical. In today’s age, single genes are sequenced regularly, quickly, and at a much lower cost. DNA sequencers have also found their applications in biomarker discovery, oncology studies, personalized medicine, forensics, and others.

Manufacturers have provided several improvements in their instruments over time, creating next-generation sequencing (NGS) technologies. Some chemical innovations have also been added in second-generation sequencing which developed and gained popularity. Even newer methods are now on the horizon. Single molecule sequencing (SMS) is an approach that bypasses amplification by PCR, a crucial step in all next-generation technologies. SMS methods interrogate a single DNA molecule, overcoming problems and biases introduced by the PCR process. The potential advantages of SMS over next-generation sequencing include faster turnaround time, longer read lengths, higher accuracy, less starting material, and lower cost.

As technology moves forward, advancements are being made toward third-generation sequencing tools which comprise real-time monitoring and nanopore sequencing of PCR activity throughout fluorescent resonant energy transfer. The benefits of these techniques comprise scalability, simplicity, rise in DNA polymerase activities and products, a reduction of miscalculation prone, and even more efficiently practicable with the ultimate goal of achieving precise real-time products.

Global Market
   The global DNA sequencing clocked a revenue of USD 5156 million in 2016 and is projected to reach USD 18,284 million in 2023, reflecting a CAGR of 19.6 percent, estimates Allied Market Research. Key drivers include diverse applications that include the detection of the genes responsible for genetic disorders and diseases such as Alzheimer’s and cystic fibrosis.

During 2016, the reagents and consumables segment dominated the market and accounted for more than 57 percent of the market. Suppliers are investing in reagents and consumables, as they generate high ROI due to the presence of a large installed base of equipment. Moreover, many government organizations like the NIH in the United States offer grants for quarterly reimbursements for the R&D of consumables, which will contribute to the growth of this market segment in the future.

Factors such as technological advancements in NGS platforms, increasing applications of NGS, growing partnerships and collaborations, increasing adoption of NGS among research laboratories and academic institutes, and the decline in the cost of sequencing are driving the growth of this market.

The year 2016–2017 has been a breakthrough year for the sequencing industry as the leading market players adopted product launches, agreements, collaborations, and partnerships as their key business strategies to ensure market dominance.

North America is estimated to command the largest share of the NGS market in 2017, followed by Europe and Asia-Pacific. Emerging markets are expected to offer significant growth opportunities owing to the improving healthcare infrastructure, government funding for translational research, and rising partnerships and agreements among market players.

Research Updates
The DNA sequencers industry is witnessing a revolutionary era with the technology stepping up multiple notches. These advancements have opened new horizons for the researchers for more highly powered experiments at the depth required to discover rare genetic variants. NGS technologies have the potential to conduct large-scale genomics projects with greater sample volumes and more breadth and depth in the genome. These sequencers will open up new markets by making routine a wide range of applications from ultra-deep sequencing of matched tumor–normal pairs, to large-scale variant discovery studies associated with complex diseases, and low-pass sequencing of seed banks to select for specific traits.

A collaborative group of researchers from Oxford University’s Wellcome Trust Centre for Human Genetics (WTCHG) and Genomics plc has announced the first sequencing and analysis of multiple human genomes using nanopore technology last year.

These initiatives mark the potential of nanopore sequencers for the whole-genome sequencing (WGS) in humans. As the throughput of next-generation sequencers continues to improve and the cost of reagents declines, WGS becomes increasingly cost effective, making it a realistic possibility for use in a clinical setting.

The application of DNA sequencers to detect cancer from circulating tumor DNA in the bloodstream holds a promising future in the development of tests for early cancer detection. The high-intensity sequencing approach scans a very broad area of the genome with high accuracy, yielding about 100 times more data than other sequencing approaches. This enormous amount of data will be instrumental in developing a blood test to detect cancer early.

Challenges and Opportunities
As with any evolving technology, many challenges come into play. Cost per experimental run, data storage, and analysis are areas of concern and limit the adoption of these technologies on a wider front. Cloud storage has become the repository solution for corralling the data generated and enables access and sharing among research labs. Leading market players continue to work with researchers to create solutions that will enable them to gain a better grasp of research results.

Clinical adoption of NGS will require regulated and approved processes and methodologies to enable clinical researchers to make fast, reliable, and accurate interpretation of results, which will in turn enable accurate patient diagnoses. With the advent of exciting tools and reagents and improved instruments, NGS continues to revolutionize how researchers explore the genome.

Future
The evolution of DNA sequencing from the nascent protocols to today’s high-throughput technologies has occurred at a breathtaking pace. DNA sequencing now commemorates its 40th anniversary, a period in which it has witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. The sequencers have been extensively and creatively repurposed; and the technologies are likely to continue to develop in the coming decades and centuries. On the basis of how quickly it has transformed biomedical research, and is beginning to transform clinical medicine, it is believed that DNA sequencing will witness longevity and high growth.

Second Opinion

NGS Supports Drug Discovery

Dr Pravin D Potdar
Faculty, Indian Dental Association
Research Fellowship Program

Since completion of human genome project in 2003, several innovative technologies and instruments are introduced in the field of medicine. Next-generation sequencing (NGS) is a parallel sequencing technology which provides a large set of sequence data in very short period of time. NGS is very much useful in characterization of target identification and disease-associated mutations in drug discovery program for accurate diagnosis of various diseases. It determines the presence of drug resistance and gets better response to medical interventions. Thus, NGS is also useful in drug discovery program.

Single nucleotide polymorphisms(SNPs) are extensively used to analyze characteristics of individual who can respond to a therapeutic agent. NGS technology is useful for large-scale screening of SNPs to determine whether new drug will be effective and safe in respective individual. Large amount of genomic sequence data obtained by NGS will allow scientists to develop novel therapeutic agents by studying specific mechanism of respective disease. This is mainly important for genetic disorders which are difficult to diagnose. NGS allows us to screen and profile large number of gene mutations involved in particular diseases in short period of time and thus unique biomarkers are identified to discover drug targets. The major goal of NGS is to developed molecular targeted therapies for cancer which kill tumour cells without harming normal cell growth resulting into reduction in side effect and thus the mortality. The identification of novel molecular targets, biomarkers, and mechanistic information by NGS fastens the drug discovery process in recent year.

Recent forecast across North America,Europe,Asia-Pacific, and the Rest of the World,the global NGS services market is expected to be doubled in next five years. In year 2017, it is almost USD 1.059 billion and will reach to USD 2.74 billion by 2022. North America accounted for the largest share followed by Europe. Due to the rapid growth in the genomic research and NGS based diagnostics in emerging Asia-Pacific countries, like ChinaandIndia, will adopt more NGS services in near future.

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