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Interview | The future of sequencing technology after ten years of application

2019-05-24

【Beijing, China】Recently, at the first China Intestinal Industry Conference, MGI was invited to attend the Sequencing Technology and Application Forum. Regarding the significance and value of sequencing technology for intestinal flora research, Ma Tao, the director of Applied Technology Support of MGI, was invited to give an interview. The following content is taken from the on-site record and the selected five topics are most concerned about the roundtable forum, thus sharing views of MGI with you.


What is the significance and value of using the sequencing technology to study the intestinal flora?


Ma Tao: Regarded as the "No.2 genome" of humans, the intestinal flora has significant impacts on our life. How to restrict these effects within the limits that we humans can control? In 2010, BGI used high-throughput sequencing to study 124 European intestinal microbes and constructed the first and the most complete human microbial gene set. This achievement was published on the cover of Nature and became one of the most influential “Top Ten Scientific and Technological Progress in the World” in the first decade of the 21st century. Since then, our understanding of intestinal microbes has reached the genetic level: by using high-throughput sequencing technology, researchers can study the association of intestinal microbes with complex diseases through the construction of intestinal microbial reference gene sets, and then conduct a series of researches and applications such as evaluation/monitoring and intervention on human intestinal health.


High-throughput sequencing technology has been applied for more than ten years. In the near future, how will the sequencing instrument and technology develop, and how should researchers respond?


Ma Tao: The development of technology and tools is actually a development that conforms to the times and needs. In practical applications, the needs for sequencing technology to be more powerful, faster, lower cost, more diversified or more miniaturized, all of which may be the trend of future development. Obviously, the response of researchers is to keep pace with the tendency, to learn continuously, and to innovate constantly.


High-throughput sequencing commercial services bring opportunities for a large number of enterprises such as MGI and Novogene. What are the current challenges and how to develop in the future?


Ma Tao: High-throughput sequencing commercial services, as the name suggests, is to serve customers with sequencing needs. Therefore, the challenge naturally comes from the increasingly diverse and increasingly personalized needs of customers. With the popularity of technology, customers receive more information and can apply this technology more creatively. It is getting more difficult for traditional, standardized and mass-produced service models to meet the growing needs of customers.


Technological innovation will inevitably bring great pressure on existing service providers, especially when facing the challenge of growing market segments. How to follow up new technologies and platforms in time?  How to develop upstream and downstream cooperation systems? How to achieve product transformation from basic research to different fields? How to expand the market by cooperation? All of these issues need industry head companies, namely innovative companies, pioneers to consider more.


In my opinion, future development will be a virtuous circle in an open, shared, non-monopoly, sequencing ecosystem that everyone can play on its own, achieving an ecologically balanced state.


In what ways will the third-generation sequencing technology help the development of microbial and microecological research? Does it mean that second-generation sequencing technology is outdated? With the popularity of three generations of sequencing technology, how to make better use of the old data of the previous second generation sequencing?


Ma Tao: Firstly, the so-called second and third generations do not have intergenerational relations. There are no worries of being replaced, being eliminated, or being outdated. In fact, there only exist the next generation compared with the "gold standard" of last generation.


Next, with the popularity of sequencing technology, how to make better use of sequencing data is a good question. As the specific micro-ecology industry is still in its infancy and needs breakthroughs in both scientific research and industry, In the current stage, it is very important to accumulate data quickly, reveal scientific laws and explore application scenarios in current stage. In other words, you must obtain the data first, then use the data to do deep mining and in-depth analysis. In terms of big data accumulation, MGI has

created a variety of independent sequencing platforms with flexible and optional flux, good data quality, controllable sequencing costs, rapid transformation of scientific research and clinical platforms, which deserves more attention.


Lastly, regarding the issue of using the long or short readings, in fact, whether it is long reading or short reading, the technology is good or not, it depends on what we want to get through sequencing technology. If our goal is to obtain high-quality long-segment DNA information, we can achieve this by using short-reading technology. For example, the StLFR technology created by MGI can bring more innovative ideas and methods to the study of intestinal microbes. Therefore, the combination of long and short read sequencing technologies may become a long-term trend in a foreseeable future.


How do domestically produced sequencers promote intestinal flora research and industrial applications?


Ma Tao: Promoting intestinal flora research and industrial applications requires the efforts of the entire industry. In this process, domestic sequencers will play as the largest platform. In 2017, the deep metagenomic sequencing of intestinal samples based on healthy populations was completed. In 2018, the world's first rat intestinal microbial reference gene set was constructed. In March 2019, the high-depth metagenomic shotgun sequencing of the fecal microbiome was completed. All of these achievements are based on MGI’s

domestically produced sequencer platform. We believe that with the joint efforts of all, the intestinal flora research and industrial application will achieve greater breakthroughs in the future.


Reference

【1】Fang C , Zhong H , Lin Y , et al. Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing[J]. GigaScience, 2017.

【2】Pan H , Guo R , Zhu J , et al. A gene catalogue of the Sprague-Dawley rat gut metagenome[J]. GigaScience, 2018.

【3】Jie Z, Liang S, Ding Q, et al. A multi-omic cohort as a reference point for promoting a healthy human gut microbiome[J]. bioRxiv, 2019.




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