Third-generation sequencing technologies are causing a new revolution in genomics as they provide a way to study genomes, transcriptomes, and metagenomes at an unprecedented resolution.
The field of genomics has expanded greatly in recent years, thanks in large part to advances in DNA sequencing technology. Technologies to determine DNA sequences have been an intense area of study since discoveries of the role of DNA as the genetic blueprint and nucleotide structures in the early to mid-1900s. Today, the ability to sequence an organism’s complete genome and its associated RNA transcripts is transforming the understanding of biological concepts such as genetic diseases, cancer mutations, genealogical and evolutionary links, and gene expression patterns, to name a few. The transition from targeted gene sequencing, to whole exome sequencing, to whole genome sequencing has only been made possible due to rapid advancements in technologies and informatics that have plummeted the cost per base of DNA sequencing and analysis. The tools of genomics have resolved the etiology of disease for previously undiagnosable conditions, identified cancer driver gene variants, and have impacted the understanding of pathophysiology for many diseases.
Forty years ago, the advent of Sanger sequencing was revolutionary as it allowed complete genome sequences to be deciphered for the first time. Although the Human Genome Projects were notable achievements, they also highlighted challenges in sequencing large genomes using Sanger sequencing, the most significant of which were time and cost. Therefore, researchers developed alternative sequencing technologies with improved speed, affordability, yield, and sensitivity, so that large and complex genomes could be efficiently sequenced to better understand population genetics and their implications. A second revolution came when next-generation sequencing (NGS) technologies appeared, which made genome sequencing much cheaper and faster. However, NGS methods have several drawbacks and pitfalls, most notably their short reads. Thus, the so-called third-generation platform has been introduced, which can produce genome assemblies of unprecedented quality.
Moreover, these technologies can directly detect epigenetic modifications on native DNA and allow whole-transcript sequencing without the need for assembly. The third-generation sequencing technologies are thus causing a new revolution in genomics as they provide a way to study genomes, transcriptomes, and metagenomes at an unprecedented resolution. Single-molecule sequencing, single-molecule real-time (SMRT) technology, high-throughput sequencing, and nanopore sequencing are some of the latest technologies. SMRT and nanopore sequencing has allowed for the first time the direct study of different types of DNA base modifications, while nanopore technology can sequence RNA directly and identify RNA base modifications.
Indian market dynamics
The Indian market in 2015 for DNA sequencers is estimated at `238.8 crore. It may be segmented as capillary sequencers and NGS. The capillary sequencers market is divided in the ratio of 53 percent instruments and 47 percent consumables, whereas the NGS constitutes 44 percent of instruments and 56 percent consumables. This is very different from 2016, when the market for NGS was skewed as 70 percent instruments and 30 percent consumables. In October 2016, MedGenome, a Bengaluru-based company into genomics research and diagnostics procured the Illumina Hiseq X Ten machine, a population scale sequencer for USD 5 million approximately. 2017 onwards, the ratio is gradually coming back to a 50:50 for instruments and consumables. Other companies who procured NGS instruments in 2017 include Institute of Genomics & Integrative Biology (IGIB), ISBT, National Institute of Biomedical Genomics (NIBMG), and Strand Life Sciences.
Moving forward, this market is expected to do well, as buyers as MedGenome penetrate Tier-II and Tier-III cities utilizing the capital they have raised to expand the clinical genomic testing market. While having raised funds for USD 30 million in financing led by Sequoia India and Sofina s.a. in August 2017 and USD 10 million from HDFC Ltd., HDFC Life, and HDFC Asset Management in March 2018, the company has announced its plans to further democratize the critical genetic tests like noninvasive prenatal screening (NIPT) and new-born genetic testing. The company also plans to establish more genetic centers in hospitals across the country to support clinicians and to enable patients to make informed decisions.
Current developments in sequencing techniques have dramatically changed the field of genomics during the present technological development, making it promising for even particular research members to generate gigantic amount of sequence data very fast at a considerably subsidized budget and expense.
High-throughput sequencing. Recent advances and developments in HTS using NGS technologies have become essential in the studies of digital gene expression profiling, in epigenomics, genomics, and transcriptomics. These technologies are capable of sequencing multiple DNA molecules in corresponding and can facilitate sequencing of hundreds of millions of DNA molecules within a short period of time.
Next-generation sequencing. Today’s complex genomic research questions demand a depth of information beyond the capacity of traditional DNA sequencing technologies. NGS has filled that gap and has become an everyday research tool to address these questions. What once took years of painstaking genetics work – if it could be done at all – can now be performed many times over in the virtual blink of an eye, at less cost and finer resolution, with the ability to process enormous sample sizes and possibility to obtain orders of magnitude more data.
Sequencing by expansion. It is an elegant, low-cost sequencing technology, with a simple workflow and rapid sample-to-measurement process times that can be configured for small, targeted sequence applications as well as large high-throughput whole genome systems.
Even though DNA sequencing technology is only about four decades old, its impact on the medical, scientific, and research fields is profound. It has undergone massive expansion in the past few years, from a rarely used research tool into an approach that has broad applications in a clinical setting. The implications of DNA sequencing are vast and promising, with a great potential for everything from learning more about the history to diagnostic and therapeutic applications. The breathtaking advances in both speed and cost of DNA sequencing will transform biology, medicine, and society. However, the challenge will be analyzing the large amounts of data that will be available in the coming years as the DNA sequencing technologies become faster and more efficient, generating larger amounts of data.