Gene dark information will break the low success rate of cancer treatment
On April 20th, Google and Verily announced the launch of a large-scale health project for four years and thousands of people to participate in the creation of a map of human health. Various analyses such as cancer liquid biopsy, genomic analysis, and intestinal microflora were performed on samples of blood, saliva, and feces of 10,000 volunteers. Disease diagnosis and individualized treatment based on precision medicine has become an inevitable trend of global medical development, and the future will not be limited to disease treatment, and the function will be advanced to a wide range of fields such as disease prevention and health care. However, behind the development of precision medicine, it faces a major problem that cannot be ignored. Human understanding of its own genetic code is still at a very early stage. Academician Chen Runsheng believes that in addition to the genetic sequence of the encoded protein of 3% of the genetic code, the dark information of the gene contained in the non-encoded RNA will provide a new vision for the diagnosis and treatment of the disease, providing a new platform for the development of drug design. It provides a new foundation for the cultivation of new varieties and new traits of animals and plants. The “2017 China Biomedical Engineering Conference†hosted by the China Biomedical Engineering Society and the Chinese Academy of Medical Sciences was held recently. The Shell Society provided full media support for the event. Chen Runsheng, an academician of the Chinese Academy of Sciences, delivered a keynote speech on "Genome, Big Data and Precision Medicine". The highlights of the speech are as follows: In 2020, precision medicine can affect China's overall GDP On January 20, 2015, US President Barack Obama delivered the 2015~2016 State of the Union address, opening the road of precision medicine research. In the past two years, China’s major projects focusing on precision medicine have also begun to establish projects. So far, there are 60 The project, with a total capital of about 1.2 billion yuan, has already begun to operate, and the next phase of precision medicine projects is also under review. Precision medicine began in the United States, entered the end of the 20th century, began an epoch-making project - deciphering human own genetic code, and then the entire biomedical research from expression to molecular age, unprecedented in the history of human science. After deciphering the genetic code, a large amount of data was accumulated, and it was found that many changes in the locus were directly related to major human diseases, which created the basis of precision medicine. Each person has 3 billion bases per cell. At present, it is possible to measure your own genetic code in China by spending 5000~6000. It is expected that by the end of this year or early next year, you can measure your own genetic code by spending 100 dollars. It is believed that the acquisition of molecular level information represented by genome sequencing will be very fast. It becomes a routine means of detection, which will flood into medical units and become the basis of medical and biomedical research. The essence of precision medicine is a combination of big data and medicine. The only difference between precision medicine and traditional medicine is that it increases the molecular level data represented by the genome, which is the influx of a large number of omics data. . The big data of omics contains two meanings. The first layer is the data acquisition represented by the genome. However, because these data are too large, it is necessary to guide the connection with biomedicine. The method of modern big data analysis must be used to mine the connotation of massive data. So, another layer is the deep mining of the biological and medical connotations of big data. The introduction of omics data into the clinic, the far-reaching significance of the future is the conceptual and essential changes in the medical system: the transition from current treatment to future health protection. The precise meaning of the future is that in any living period of any person, the omics data can be measured, and the health status of the body can be properly measured and intervened according to the measurement. Therefore, the medical system in the future precise sense is health for the whole people. The security system, rather than the modern diagnosis and treatment system for patients, may lead to the emergence of corresponding emerging industries due to conceptual changes. It is estimated that the corresponding global industrial market in 2018 will reach 223.8 billion US dollars. It is estimated that by 2020, the corresponding industry of precision medicine can reach 1.8 trillion US dollars, which is enough to affect the country's overall GDP and has far-reaching effects. Therefore, precision medicine has become a new strategic high point of technological competition and leading the country's development trend. The United States is also actively promoting field research. The United States is preparing to measure the genetic code of 1 million free people. Now it has measured 680,000 people. Both the European Union and Japan are developing precision medicine programs. Precision medicine four sub-sector industry prospects In what ways does precision medicine begin to promote the development of corresponding new industries? In at least four aspects, our domestic counterparts have already achieved: The first is the emergence of a mass database and sample library industry. Precision medicine is the acquisition, storage and use of samples from 100,000 to 1 million, corresponding to the storage of millions of data; it is estimated that it can be reached in the near future. The scale of 10 billion US dollars; according to statistics, the market value of the biological sample bank in 2015 will exceed 2.25 billion US dollars. By 2018, the total market for bio-big data has grown to 7.6 billion U.S. dollars, with a compound annual growth rate of 71.6%. The commercial share of biodata has been initially reflected. In January 2015, Roche's pharmaceutical subsidiary Genetech injected $60 million into 23 and me to share the genetic data of Parkinson's patients collected by 23 and me, and to develop treatment plans for Parkinson's disease based on data information; The second is the acquisition of omics data represented by genome sequencing. According to BBC research data, the global gene sequencing market has increased from US$7.941 million in 2007 to US$4.5 billion in 2013. It is expected that the global market will continue in the next few years. It will continue to maintain rapid growth, reaching $11.7 billion in 2018, but as the cost of sequencing declines, it will become a project that can be realized by the whole people, but I think the corresponding funds are definitely more than $11.7 billion, much larger; The third molecular diagnosis is also the most cost-effective industry. It is based on massive data mining new disease molecular markers and new therapeutic drug targets. Although complex but cost-effective, it has become a new hot spot in the biomedical industry. In general, new drugs appear, and the market for single-agent drugs can reach the order of 10 billion US dollars. After the emergence of massive data, it will bring new targets and drug treatment targets for the diagnosis of numerous diseases; according to Markets and Markets, the market value of the global market in 2018 is estimated. Will reach 7.9 billion US dollars, the compound annual growth rate between 2013 and 2018 is 9.7%; The market for individualized treatment based on the concept of precision medicine is expanding. The top ten commercial insurance companies in the United States have included more than 50 individual disease detection and molecular testing items in medical insurance. The huge market space has attracted many pharmaceutical companies to carry out research and development. Individualized medical products are on the market. As of 2013, the US FDA has approved more than 100 individualized drugs with a focus on chronic diseases and cancer. The fourth industry is a new medical facility, such as health facilities, health workers, and a large health industry circle. This industry circle is estimated to reach 200 billion US dollars in 2018. The above four industries have emerged in China and I believe that they will develop better in the future. What preparations do you need to achieve precision medicine? There are two foundations. One is to group big data. Precision medicine is a combination of big data and clinical medicine, so it is necessary to obtain big data for group learning. The second is to build microscopic information at the molecular level and between disease phenotypes. Association. After the establishment of the two foundations, combined with modern imaging and biochemistry, precision medicine can develop better. Industrial Opportunities Behind Gene Dark Information What is the current stage of precision medicine? Personal opinion is that precision medicine has just started. In the acquisition and analysis of omics data, there are major challenges that are difficult to overcome in the processing of big data. There are many challenges. I will only talk about one challenge today. It can be seen that precision medicine can only be just beginning. The genome has a lot of dark information. The genetic code is very easy to measure. At this stage, 6000 pieces can be measured. In the future, 600~700 pieces can be measured, and 3x109 genetic information can be obtained. The question is, for such a genetic code, where is our knowledge front, and how much can it be explained? At present, for the interpretation of the genome, the current level of human beings is that the part that can be completely explained in terms of law is about 3% of the genetic code. In other words, scientists around the world can measure the genetic code, only 3% can accurately explain, which is the gene encoding the protein. Another 97% of us are called non-coding regions in the genetic code. So far, this is dark and we still can't understand. In such a context, how to be precise? 97% of the non-coding regions do not know what to do, and when it changes, its biological significance is unknown. Let me take a document as an example. It was published in Science in 2010. When the human genome was first deciphered in 2001, scientists thought that 100,000 bases could find 100,000 genes, but surprisingly only less than 35,000 were found. The protein coding region only accounts for 1.5% of the entire genome. Isn't the rest of the genome dark matter useless? So this is a very serious problem. Many high-end people are testing their genetic code. It is not useless. Only 3% can be used and analyzed. This is the current situation. In terms of precision medicine, our genetic code is dark, but from the basic research, there are opportunities for unlimited innovation. This 97% has created a lot of original innovation opportunities for us: In the first aspect, in terms of the genetic code, the human genetic code is compared with other genetic codes with different evolution levels, and Coding represents a genetic code that has been learned regularly. The Non-coding non-coding area represents a part of the function that has not been known so far. It can be seen that the single-cell prokaryotic E. coli is such a simple and low-lying organism, and 85% of the genetic code is used to encode the protein, so after the measurement, it is generally known how it lives. Yeast, a single-cell eukaryote, is slightly higher, with fewer protein fractions (70%) and non-coding regions (28%); nematodes, simple multicellular, with only 960 cells, but already The higher multicellular organisms used to encode only 28% of the protein; the fruit fly, which is already an insect, has only 17% of the coding part, 1.5% of the human coding part, and 98% of the non-coding area. This suggests that we may think that from biological to simple to complex, low to high, more and more genes, more and more proteins, on the contrary, this is wrong, in fact, I do not know that the non-coding part of the function has increased by leaps and bounds. It shows that from the perspective of evolutionary logic, non-coding sequences must have more important biological functions, and must be associated with higher and more complex functions of organisms. In the second aspect, some people think that there is a lot of redundancy in the genetic code, which may be normal. But 97% of the information has occurred, is it active, and biologically, does it have a transcript? If there are different activities, it proves that 97% is active, active, and working all the time. This is indeed the case. Transcripts from 97% of the sequences have been found in dozens of laboratories around the world, but this part of the transcript does not make protein, but functions in the form of RNA. This result fully demonstrates that 97% of the non-coding regions are important components of biological function. Most of the transcripts are non-coding RNAs, and the most important difference between species is non-coding RNA. Below, I exemplify the relationship between non-coding RNA and several diseases, taking the discovery of individual functional components and tumor-related studies as an example. The first is PCGEM1 (prostate-specific RNA gene with cell growth-promoting function), which is derived from 97% of transcripts, which can lead to prostate cancer; the second source, 97% of the transcript is called HIS-1, the gene is Highly conserved in vertebrates, it can cause leukemia in mice, and can control cell cycle progression in the oncogenic pathway; the third is MALAT-1, which can lead to non-small cell lung cancer, which is the most common tumor in China. Rates are increasing every year, 80% of which are non-small cell lung cancer. These three examples show that the cause of the tumor can be completely derived from the non-coding region. Our current clinical indicators in all hospitals are from 3%, the protein-encoded gene portion, and the targeted drugs for treatment are also targeted at 3%, 97% of the genes. Tumors caused by mutations are not found at the current level and cannot be treated. This is a big problem encountered in cancer treatment. The success rate of tumor molecular markers is also very well understood. 97% are not included in the diagnosis and treatment of diseases. More than tumors, cardiovascular and cerebrovascular diseases, and metabolic diseases are also 97. % of non-coding genes are at work. Explain that it is necessary to develop a huge field of 97% at the molecular level to accurately predict disease, and it is related to all diseases. This is the result of our joint research with the Hejie team of Concord. The tumor markers are found in 97%, which can well distinguish the stage and prognosis of esophageal squamous cell carcinoma. In addition, 97% of transcripts can be found, which can affect tumors. Stem cell dryness (long-chain non-coding RNA in tumor stem cells IncTCF7 can promote self-renewal of human liver cancer stem cells, the results of 2015 research); and recently published research results, found that 97% of transcripts have a common immune system Great role (long non-coding nucleic acid IncKdm2b regulates lymphocyte mechanisms, published in Nature Immunology in 2017). There is also a non-coding transcript H19, doctors must be clear, P53 is a very important protein, is our protector. H19 in 97% is also our protector. If it does not mutate, it can cause apoptosis of certain cancerous cells through a cell-like pathway. The data indicates that many non-coding genes have yet to be discovered. There are about 20,000 components in 3% of humans, and 97% of them have no data. However, it can be exemplified by mice. A few years ago, the Japanese Institute of Genetics (RIKEN) obtained clones of all transcripts of mice, and obtained about 181,000 full-length RNA transcripts, of which only about 20,000 transcripts were encoded. Approximately 161,000 transcripts are all attributed to non-coding RNA. A new component has never been found to be able to be published in the three core journals CNS, which is the opportunity for original innovation. From past experience, in this part of the human genome of 3%, there are a total of 50 Nobel Prize winners, and in the face of the undeveloped 97%, it is expected to create more Nobel Prize winners. Therefore, the study of non-coding regions will provide a new vision for the diagnosis and treatment of diseases, providing a new platform for the development of drug design, providing a new foundation for the cultivation of new varieties and new traits of animals and plants. 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