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On June 17th, the genetic sequencing related targets in the pharmaceutical sector showed significant gains in the news impact of “three major generations of sequencing technology breakthroughs.†We also received more inquiries from investors about the background and opinions of relevant news. To this end, we summarize the development history, principles, advantages and disadvantages of the three generations of gene sequencing, as well as the companies that are laid out at home and abroad in combination with various aspects of the data (that is, this is a three-generation sequencing "Popular"). In addition, we have carried out a free translation of the original part of the English literature, in order to have a shallow understanding of the latest algorithms and industry technology, and there is a place that does not conform to the original meaning.
News background:
Ma Zhanshan, a researcher at the Kunming Institute of Zoology, Chinese Academy of Sciences, and Dr. Ye Chengyu from the University of Maryland, USA, have once again made important breakthroughs in the field of gene sequencing. The cooperation team recently released a software code-named Sparc, which developed a "linear complexity algorithm based on sparse decomposition" for the third-generation gene sequencer with a hardware error rate of 15%-40%. The Sparc software is based on this. The new algorithm is complete. Using Pac Bio data with a 30x depth of sequencing, Sparc can achieve an error rate of less than 0.5%; using the more challenging Oxford Nanopore data, Sparc can achieve an error rate similar to NGS. Compared to current methods, Sparc is more accurate in calculating consistent sequences and saves 80% of memory and time. This important breakthrough provides another key software technology for advancing the genetic sequencing technology to the industrial upgrading of three generations of technology.
Overall view:
We believe that the three-generation sequencing technology represented by Helicos' Heliscope single-molecule sequencer, Pacific Biosciences' SMRT technology and Oxford Nanopore Technologies' nanopore single-molecule technology has gradually matured after years of development. Although the current technology has high cost, high error rate, and insufficient bioinformatics analysis software, it has obvious advantages in terms of read length and sequencing speed. The third-generation sequencing equipment has achieved stability and miniaturization. In the future, with the improvement of accuracy, parallel sequencing ability and enzyme activity, the third-generation sequencing technology is an important technology trend in the future development, and large-scale commercialization will be the general trend.
Specific to the Sparc algorithm, according to the literature we believe that it has the potential to help improve sequencing accuracy and reduce the cost of sequencing (especially when mixing NGS and 3GS data, or can significantly reduce costs), it is worthy of attention. However, it remains to be seen whether commercialization can be achieved (the published PeerJ journals are not first-line journals by impact factor and contribution hit rate). For the precision medical sector, we believe that although precision medical treatment is flat under the influence of high valuations and some industry events (such as the Wei Zexi incident), there is no shortage of catalysts. On March 8, 2016, the state released the Ministry of Science and Technology. Notice on the publication of the 2016 special project declaration guidelines for key national special research and development programs, such as precision medical research. Considering that the relevant target has experienced a large decline since the beginning of the year, if the subsequent market risk appetite is improved and there is a continuous catalyst (such as the introduction of new industry plans or related enterprises to receive special support from the Ministry of Science and Technology for precision medical research), it is also an area of ​​concern. At the same time, it is recommended to pay attention to some new technology themes that have not been fully fermented in the early stage (such as liquid biopsy), and focus on new open source, Livzon Group, Runda Medical, Dean Diagnostics, and Meikang Bio.
Risk warning: the absolute value of the relevant target is high, and the policy catalysis and technological innovation are uncertain.
The background of the first and third generation sequencing industry:
1. History of the development of gene sequencing technology
In 1986, the first commercial gene sequencing equipment appeared, 19 years apart, the second generation of sequencing equipment appeared, from the second generation equipment to the third generation equipment only took 5 years, indicating that the speed of genetic sequencing equipment is faster. The first generation of sequencing technology, based on the Sanger double-deoxygenation termination sequencing principle, combined with fluorescent labeling and capillary array electrophoresis technology to achieve sequencing automation, the basic method is chain termination or degradation, the human genome project is based on a generation of sequencing technology. The second generation of sequencing technology, the early representative platform includes Illumina's Solexa, LifeTechnologies' Solid, Roche's 454 platform, etc. The current second-generation sequencing equipment has greatly improved the throughput and accuracy, and the sequencing cost is also followed. It has fallen sharply and has become the mainstream of commercial sequencing. The third-generation sequencing technology, also known as single-molecule DNA sequencing, is the principle of distinguishing base signal differences by means of modern optics, polymers, nanotechnology, etc., in order to achieve direct reading of sequence information, three generations of sequencing equipment in DNA sequences. Fragment read length is better than second-generation equipment, but it is worse than second-generation equipment in accuracy. With the improvement of technology in the future, the third-generation sequencing equipment will be more stable and mature.
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