Massive parallel sequencing (MPS) technology known as next-generation sequencing (NGS) has revolutionized the life sciences. With its ultra-high throughput, scalability and speed, NGS enables researchers to study biological systems at a level never before available.
Sequencing is the general name for methods that allow you to establish the sequence of nucleotides in a DNA molecule.
The most complex topical issues of genomic research require such a depth and volume of information that exceed the capabilities of previously existing DNA sequencing technologies. Next Generation Sequencing (NGS) has filled this gap and has become an indispensable tool for day-to-day research today.
What NGS can do
The emergence of NGS technology has radically changed the very nature of the problems that are now available for scientists to solve. Innovative sample preparation and output analysis methods provide a very wide range of applications. NGS allows:
- Rapid determination of the order of nucleotides in small specified regions of the genome or in entire genomes;
- Study of the sequence of target areas at very great depths;
- RNA sequencing to detect new RNA variants and splicing sites, as well as quantify the level of mRNA expression;
- Analysis of epigenetic factors such as DNA methylation of the genome or the interaction between protein and DNA;
- Sequencing of cancer samples to study rare somatic mutations, tumor subclones and more;
- Study of the diversity of microbial communities in humans and in the environment.
Affordable whole genome sequencing
The Human Genome Project, which used the Sanger sequencing method, which is the most widely used in the last 40 years, based on capillary electrophoresis, took more than 10 years and cost almost 3 billion dollars.
The Human Genome is an international research project, the main goal of which was to determine the sequence of nucleotides that make up DNA and to identify 20-25 thousand genes in the human genome. It was held between 1990 and 2003.
Next-generation sequencing, in turn, makes full-scale whole genome sequencing (WGS) available to the ordinary researcher. It allows scientists to analyze the entire human genome in one experiment and perform WGS on tens of thousands of genomes in one year.
Wide dynamic range for gene expression profiling
NGS-based RNA sequencing allows researchers to overcome the inefficiencies of outdated technologies such as DNA microarrays. Measurement of gene expression using DNA microarrays is limited due to noise at the lower level and signal saturation at the upper level. In turn, next generation sequencing quantifies discrete digital sequences. This provides a wider dynamic range.
Due to its wide range, NGS has proven invaluable for biomarker research in the analysis of cancers. With the help of NGS, scientists began to study tumors, identifying very subtle and previously undetected differences between the types of this disease. Previously, the tumors seemed to be just identical. Information about their specificity has made it possible to more specifically study how tumors respond to various types of treatment.
Custom resolution for target subset
Targeted sequencing allows the study of gene subsets of interest or specific regions of the genome, flexibly focusing resolution. The researcher can choose whether to surface scan multiple samples or sequester fewer samples at a greater depth. This makes it possible to identify rare sequences in individual regions of the genome.
NGS equipment and research market
According to forecasts, by 2022 the global NGS equipment market will be between $10.5 billion and $11.9 billion. The growth in demand for NGS systems is due to the progress and increasing availability of platform technologies, the development of partnerships between manufacturers and institutions, and most importantly, the decrease in the cost of sequencing.
Thanks to advances in instrumentation, the cost of gene sequencing has dropped by several orders of magnitude over the past decade. The study, which cost $ 10 million at the end of 2007, required no more than $5,000 by the end of 2013. In 2014, Illumina CEO Jay Flatley unveiled the new HiSeq X10 instrument, announcing a “Complete Genome Survey for just $1,000.” Since then, the pace of technology availability has only accelerated.
Leading companies
This list does not include numerous companies that are dynamically growing in the NGS market, but formed through acquisitions or partnerships and do not have their own history of technology development.
1. Illumina (USA)
The company is headquartered in San Diego, California. It has existed since 1998 and focuses on the development, production and implementation of systems for the analysis of genetic diversity and biological functions. After dominating the high-tech NGS sector for several years, Illumina announced the launch of the low-cost iSeq 100 line in January 2018. The company touts its latest sequencers as devices that “make NGS available to virtually any laboratory.” In partnership with the Chinese company KingMed Diagnostics, Illumina specialists are engaged in research in the field of oncology and hereditary diseases.
2. Thermo Fisher Scientific (USA)
An American biotech product development company headquartered in Waltham, Massachusetts. The sales volume of NGS devices in it is about a quarter of the turnover of the entire business. The new Ion GeneStudio S5 is interesting in that it allows multiple instruments to be combined into one platform when conducting research, thus offering convenient scaling. In addition to releasing its own instruments, Thermo Fisher Scientific announced last year that it will begin offering its Ion AmpliSeq technology (panels for creating amplicon libraries) to researchers using the Illumina NGS platforms.
3. BGI Genomics (China)
BGI is a genome sequencing company headquartered in Shenzhen, Guangdong province. It was created in 1999 specifically to participate in the Human Genome Project and is today the world’s largest research center for genetics. BGI subsidiary MGI Tech develops the MGISEQ series of full genome NGS sequencers. In January 2018 BGI launched a project called Life Periodic Plan. His goal is to use NGS to digitize data on all animals and plants on Earth and, ultimately, to find out the hidden laws of life. The implementation of this project will help protect endangered animals and plants, as well as maintain ecological balance and the diversity of life on the planet.
4. Agilent Technologies (USA)
Agilent Technologies is an American manufacturer of measuring equipment, electronic medical equipment and chemical analysis equipment, which was spun off from Hewlett-Packard in 1999. The Agilent lab focuses on research and development in MEMS, nanotechnology, and biochemistry. In the summer of 2017, Agilent acquired a portfolio of molecular and exemplary coding patents from Population Genetics Technologies, which management believes will improve the accuracy and sensitivity of its NGS systems.
5. Qiagen (Netherlands)
The Dutch holding Qiagen, headquartered in Hilden (Germany), includes about 30 companies engaged in the production of equipment for molecular diagnostics, scientific and pharmaceutical research. Qiagen’s flagship next-generation sequencing system is the GeneReader Platform. In 2018, Qiagen partnered with US genetic testing company Natera to develop cell-free DNA tests focused on prenatal screening.
6. Macrogen (South Korea)
A biotech company headquartered in Seoul. It is the largest sequencing company in South Korea and one of the world leaders in the production of NGS systems. The company has branches in the USA and Europe.
7. Pacific Biosciences (USA)
PacBio describes its NGS platform as single-molecule real-time sequencing (SMRT). Launched in 2015, the Sequel sequencing system has enjoyed strong sales in China, which accounts for a significant portion of PacBio’s business.
8. Genewiz (USA)
Genewiz specializes in genomics research services and is one of the fastest growing private companies. It was founded in 1999 and is located in New Jersey, USA. In 2017, Genewiz expanded its clinical genomics expertise by launching the CLIA Sanger Sequencing laboratory sequencing service.