Academician Chen Runsheng of the Chinese Academy of Sciences
The leading role of bioinformatics in research fields such as biomedicine has become increasingly prominent. With the development of big data, bioinformatics research will also make more contributions to the development of precision medicine and human health
Bioinformatics will guide the transition from modern medicine based on diagnosis and treatment to precision medicine based on health security
Wen | Sun Yinglan and Guo Yuqi, reporters of the "Outlook" news weekly
In May this year, the National Development and Reform Commission issued the 14th Five-Year Plan for the Development of the Bioe economy (hereinafter referred to as the "Plan"). The "Plan" proposes that during the "14th Five-Year Plan" period, promote the integration and innovation of biotechnology and information technology, accelerate the development of biomedicine, biological breeding, biological materials, bioenergy and other industries, and make the bioeconomy bigger and stronger. In this regard, Chen Runsheng, director of the Academic Committee of the Key Laboratory of Nucleic Acid Biology of the Chinese Academy of Sciences and academician of the Chinese Academy of Sciences, who has long been engaged in life science research, said that the promulgation of the "Plan" will play a role in promoting the transformation of research and scientific research achievements in related fields.
Chen Runsheng is one of the earliest researchers engaged in theoretical biology, bioinformatics and non-coding RNA research in mainland China, participated in the assembly and gene labeling of the B4 genome sequence of the first complete genome spring thermophila in mainland China, participated in the research of the "1% project" of the human genome and the rice genome work sketch, built two databases with important influence in the field of non-coding RNA in the world, and was the first person to teach "Bioinformatics" in China. He was awarded the first Lifetime Achievement Award in Bioinformatics of China by the Chinese Society of Bioinformatics.
In an interview with Lookout Newsweek, he said that bioinformatics is booming in China, has produced a large number of important research results, and its leading role in biomedicine and other fields has become increasingly prominent. With the development of big data, bioinformatics research will also contribute to the precision development of medical treatment and human health.
Deciphering the genetic code of humanity gave birth to new disciplines
Lookout: The Human Genome Project has been hailed as the "Moon Landing Project" in the life sciences. Why start this program?
Chen Runsheng: The Human Genome Project was officially launched in 1990, and its essence is to decipher the human genetic code, that is, to sequence the arrangement and combination of about 3 billion base pairs (genetic code) of human cellular DNA, and to put together a complete human genome map to study human growth and development and the diagnosis, treatment and prevention of diseases.
In September 1999, China became the sixth country to participate in the program, after the United States, Britain, Japan, France and Germany. China is responsible for the determination and analysis of the region on the short arm of chromosome 3 from telomere to labeled D3S3610 in the Human Genome Project about 30 centimoles (equivalent to 30 million nucleotides), so it is called the Human Genome Project "1% Project". In August 2001, Chinese scientists completed the gene sequence map of the "1% Project" two years ahead of schedule with high quality.
Lookout: What is Bioinformatics? Why is there no bioinformatics without genomic research?
Chen Runsheng: Bioinformatics is a new discipline that has emerged with the implementation of the Human Genome Project.
The human genome consists of about 3 billion base pairs. Scientists first have to cut it into tens of millions of small segments, and after each small segment is sequenced, they use specially written programs to operate on a large computer, and then re-assemble them, the process is very complicated, and a new discipline needs to be established. In addition, how to store, organize, and process the big data generated in the process, and how to provide it to everyone for use, these problems also need to be solved. More importantly, it is necessary to analyze genomic big data and dig out knowledge related to human growth, development and disease, which leads to bioinformatics.
It can be said that bioinformatics is an emerging interdisciplinary discipline integrating mathematics, physics, computer and life sciences, medicine, pharmacy and other disciplines, which is bound to the research of the human genome and serves the deciphering of the human genetic code. Through the acquisition, processing, processing, distribution, analysis and interpretation of genomic information, scientists can understand human growth and development and disease occurrence from the molecular level, which is a progress in the field of human biological research, which makes the entire biomedical science enter the era of big data.
Bioinformatics promotes paradigm shifts in healthcare systems
"Lookout": What are the major achievements in mainland bioinformatics research?
Chen Runsheng: Bioinformatics started in the late 1980s in the mainland and has developed rapidly since then. After completing the "1% Project" of the Human Genome Project, mainland scientists have carried out gene sequencing research on plants, animals, microorganisms, etc., and completed the "Thousand Human Genome Project" and other work. The number of genomes sequenced on the continent is also the largest in the world.
After 40 years of development, genomic research has been "multiplied" to all aspects of biomedicine, as long as it is at the molecular level, it is inseparable from the genome, and the research and development of nucleic acid vaccines and nucleic acid drugs are based on the results of genomic research. More importantly, it will guide the transition from modern medicine based on diagnosis and treatment to the stage of precision medicine based on health security.
Lookout: Why is bioinformatics promoting a paradigm shift in the healthcare system?
Chen Runsheng: The current medical model is mainly based on treatment, and this model is to serve patients. The use of bioinformatics means, through the analysis of genetic big data, can understand the risk factors of human diseases in advance, and prevent and interfere; The whole life cycle of a person from birth to death can also be monitored to ensure human health.
Therefore, driven by big data, the health model of human society has changed from the current diagnosis and treatment model to a universal, full-time prevention and guarantee model. Medical-related laws and regulations, drug management, social health care systems, etc. will change accordingly, which is equivalent to completing a paradigm change in the medical system and laying the foundation for precision medicine.
Academician Chen Runsheng (first from the left) discusses the results of the experiment with the students
Precision medicine faces challenges
"Lookout": Nowadays, precision medicine research has become a new round of scientific and technological competition between countries and a strategic commanding height leading the trend of international development. What is at its core?
Chen Runsheng: Since then-US President Barack Obama first proposed the concept of "precision medicine" in his annual State of the Union address in 2015, countries around the world have begun to chase related concepts and industries. Precision medicine and precision medicine are consistent, both refer to the entire medical system, from diagnosis and treatment to health security, from the hospital, doctor diagnosis and treatment of the model to the health security, health assessment and health intervention based mode. The health care system will face the whole population and can make health decisions for anyone, which is also a change brought about by precision medicine. And its core is the combination of omics big data and medicine.
Lookout: What are the basic conditions for the development of precision medicine?
Chen Runsheng: Precision medicine mainly refers to accurate diagnosis, precise medication and precise treatment. The basis of "precision" is first of all omic big data.
Human genetic code as an omics, there is a genome, through sequencing and a series of "groups" such as proteomes, transcriptomes, epithemic groups, spatial groups, etc., a genome brings omics big data - different levels of life activities have become measurable, which also brings different levels of information, and omics big data has emerged. When this new knowledge is fused with the doctor's original knowledge, the doctor will make more accurate judgments.
Secondly, with the emergence of omics big data, it is also necessary to have a scientific thinking in the data age, that is, to combine the changes in the molecular basis with the current imaging and biochemistry, because precision medicine is based on modern clinical foundations. For example, the original data that was not used as big data has also become big data, such as electronic medical records, data provided by wearable devices with monitoring human life indicators, physiological and biochemical indicators, imaging, dynamic data of patients and other individual data to be collected and sorted, and these complex, multi-scale, multi-variable, and highly heterogeneous data are extracted for analysis to find out the problems of regularity. It is also necessary to develop a series of technologies and methods for the interpretation of biomedical information. With these foundations, omics big data can be applied to diagnosis and treatment, and combined with imaging, laboratory science and doctors' clinical diagnosis practice, etc., to improve the accuracy of diagnosis and treatment to a greater extent.
Entering the era of big data, it is not only necessary to provide the information of omics big data that was not available in the past to biomedical workers, but also to turn the isolated individual data of the past into related big data that can be analyzed together. This gives a collection of big data that existed horizontally and vertically that could not be obtained before the advent of human genome research. Analyzing and deciphering the life code hidden behind these biological big data will make precision medicine gradually turn from ideal to reality.
Lookout: What are the difficulties and challenges facing the development of precision medicine?
Chen Runsheng: Measured by the core of precision medicine, the mainland is still far from reaching the goal of precision medicine. From the research level, the biggest challenge is the "dark information" in the genome.
The human genetic code is measurable, but at present, humans can really decipher and understand this part of the genetic code fundamentally and regularly does not exceed 3% of the total human genome, and the starting point of precision medicine is to analyze and apply this 3%. The remaining 97% of the genetic code, whose biological role is still only partially mastered and partially understood, deciphering and analyzing these "dark information" will be very slow, but very critical.
The second challenge comes from biological big data. The data source in the mainland is very large, but from the perspective of sample sources, it is difficult to obtain a specific sample to do the research of a related disease. For example, to study lung cancer, it is very difficult to collect lung cancer samples. Like tumors, cardiovascular and cerebrovascular diseases, are polygenic diseases, its independent variables are hundreds of thousands, to get this magnitude of samples for special research, as a research group is difficult to do.
The same disease, the microscopic situation of occurrence is also different. For example, the same lung cancer patients, the lesion distribution site is different, the number is different, the change is not the same. Well, the same disease, what is the common molecular basis, what is the individual difference, this needs to be defined in a new omics sense. This is the third challenge.
In addition, it is not only the changes of each gene that affect the occurrence of a certain disease, but also the interaction between genes. Therefore, it is also necessary to consider the interaction of various genetic codes. That is to say, a living organism, which has complex networks including signaling, macromolecular interaction, regulation, etc., are dynamic and directed. A dynamic, directed nonlinear network is complex, and how to parse it is also a difficult challenge.
Lookout: Does that also mean significant innovation opportunities?
Chen Runsheng: Yes. In human genome research, scientists have only deciphered 3% of the genetic code, which is not enough for "precision", but deciphering only 3% of the genetic code has led to countless new discoveries for the life sciences and great developments for biomedicine, deciphering 97% of non-coding sequences is more challenging and means more opportunities.
Today, the study of non-coding RNA has become a hot topic in the field of international scientific research. In terms of genome research, measurement and analysis, the mainland is in the same square matrix as countries and regions such as Europe and the United States. In the research of non-coding genetics, we and foreign scientists also have their own advantages and progress at the same time, and in some aspects we are still ahead.
The earliest non-coding research I carried out in China was based on the naïve logical judgment that "the human genome cannot use only 3% of the genetic code to create proteins, and other sequences are not used". As early as 1993, I turned all my research team to 97% non-coding research, which also promoted domestic non-coding research. The noncode database we have built to include non-coding RNA and its genes, and the database NPInter, which includes the interaction of non-coding RNA with other biological macromolecules, have become very influential databases in the field of non-coding RNA.
"Lookout": What problems should the mainland pay attention to in the development of precision medicine?
Chen Runsheng: First of all, share big data and large samples.
At present, there are a large number of biomedical data in various places, hospitals, and medical colleges, and how to achieve data sharing at the national level is a scientific, technical and management problem.
From the data level, to carry out data mining and analysis, there must first be big data, which requires a centralized management of data institutional mechanism, and needs to improve the data sharing mechanism provided by various regions and medical units.
The second is the issue of intellectual property rights. This is a deeper problem in data sharing and communication. It should be deployed from the national strategic level, and formulate policies and regulations related to big data to solve problems in big data management and sharing.
At present, bioinformatics, which has developed with the development of genomics, has gone through the "sequencing genome stage" and is entering the functional genome and integrated genome stage (also known as the "systems biology stage"). This also shows that bioinformatics has richer connotations, more diversified tools, and more and more extensive uses in the future. From the perspective of people's livelihood alone, its development has led to the development of biomedicine and biomedical industries, such as the research and development of nucleic acid vaccines and nucleic acid drugs. With the development of the bioeconomy, the biomedical industry is expected to enter the fast lane of development and will certainly make more contributions to human health. ■