With the rapid improvement of human genome sequencing technology, the rapid development of biomedical analysis technology, and the increasing improvement of big data analysis tools, we are entering a brand new era of healthcare - precision medicine.
Precision medicine is a customized medical model based on the individual, which is based on the individual's genomic and genetic information, and takes the environment, lifestyle, past medical history, and diagnostic and treatment modalities as the tracking object to collect all-around, quantifiable, prospective, and time-sensitive individual data, and then analyzes the data comprehensively to form valuable medical information, Through the comprehensive analysis and mining of data, valuable medical information is formed, and the optimal solution for the individual is finally designed.
Figure 1. Precision medicine: customized and quantified medical model based on "individuals"
Gene sequencing technology has become the mainstream technology for obtaining human genome data in genetic testing technology by virtue of its advantages of high sensitivity, high precision and throughput, and low price. By combining the genomic data with the vital signs information obtained from wireless biosensors (e.g., blood pressure, heartbeat, brainwave, body temperature, etc.), individual information from imaging devices (e.g., CT, MRI, ultrasound, etc.), and traditional medical data, Precision Medicine provides a new customized medical treatment for individuals.
The era of "one-size-fits-all" treatments has become obsolete, and the need for precision medicine is urgent
Traditional medicine's pain points have given rise to the need for precision medicine. Traditional evidence-based medicine combines a clinician's personal experience and objective scientific evidence to treat patients with the same symptoms with the same dosage of the same drug, but the results vary widely. Conventional treatment protocols have shown up to 75% inefficiency for tumors, 43% for diabetes, and 38% for depression. People are gradually realizing that the occurrence of most diseases is the result of their own genetic code and the external environment **** the same action.
Precision medicine, with the help of monitorable genetic and environmental information, provides customized and optimized treatment plans for individuals, enhances existing treatments, and promises effective prevention as far as possible before the onset of disease.
Figure 2. "One-size-fits-all" treatment in traditional medicine leads to high drug inefficiency
Precision medicine, with its four major features of quantification, individualization, ex ante prevention, and continuity, is an important innovation in traditional medicine, which further solves the pain points of traditional medicine and avoids the need for doctors to "see the forest for the trees" due to the fact that they can't see the forest for the trees.
Precision medicine is an important innovation to traditional medicine, which further solves the pain points of traditional medicine and prevents doctors from overly relying on subjective experiences, descriptions, and mass data of evidence-based medicine due to "not seeing the forest for the trees," resulting in low efficiency of diagnosis and treatment of individuals, high side effects, and hasty measures after the fact. Precision medicine has a wide range of social benefits, as it improves medical efficiency and reduces the high cost of irrational medical treatment.
Figure 3: Technological development promotes the qualitative change of traditional medical care, and precision medicine is characterized by the four major features of quantification, individualization, ex ante prevention, and continuity
Gene sequencing is the foundation of precision medicine
Gene sequencing is the basis for the establishment of a large database of genomics and its analysis, which will promote the realization of precision medicine. "
Precision medicine aims to provide patients with accurate diagnosis of diseases and personalized treatment plans, as well as upgrading medical technology to the level of pre-disease prevention. The development of related technologies has two elements: 1. building "histology" big data sample libraries, such as genomics, transcriptomics, proteomics, etc.; 2. exploring the correlation between genotypes and sample phenotypes. Through bioinformatics analysis and genetic diagnosis, we can establish the correlation between genetic information and data from clinical tests and imaging, achieve accurate disease classification and diagnosis, formulate personalized disease prevention and treatment plans, and achieve "different treatment for the same disease" and "same treatment for different diseases. "The two elements are both related to gene sequencing. Both of these elements are inextricably linked to gene sequencing.
Figure 4. Gene sequencing is the foundation of precision medicine
Five-thousandths of a percent difference in the genome between individuals can be captured by gene sequencing
The human genome consists of 3 billion pairs of bases, and the difference in the genome between different people is only five-thousandths of a percent. It is this less than 1% difference that determines human phenotypes, such as height, weight, alcohol consumption, lactose tolerance, and disease, in the same way as the external environment***. Genetic sequencing is the process of collecting blood, body fluids, or cells, using sequencing equipment to obtain the DNA sequence of the person being tested, and then using bioinformatics methods to compare that genetic information with a database of known mutations and analyze the information about the abnormal mutations in order to diagnose a disease, or even for predicting the risk of a disease.
Human genome sequencing mainly includes targeted resequencing, exome sequencing, transcriptome sequencing and whole genome sequencing. Abnormal mutations are detected by comparison with normal sequences. Abnormal mutation information is classified into 3 categories according to the number of bases mutated:
(1) mutation of a single base: single nucleotide polymorphism (SNP), (2) variation of bases below 20 bp: insertion-deletion (Indel), (3) variation of bases above 20 bp: insertion, deletion, copy-number variation (CNV ), and genomic structure variation (SV), etc.
Figure 5. Human whole genome, exome and transcriptome level differentiation
Gene sequencing is the foundation and mainstream technology of genetic testing
Genetic testing technology, which applies molecular biology to detect changes in the structure or expression level of the genetic material in the body of a patient, in order to achieve precise diagnosis and thus guide a more optimal treatment plan. Currently, common means of genetic testing include polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), Gene Chip, transcription-mediated amplification (TMA), and gene sequencing, among which gene sequencing is the foundation and mainstream technology of the other four testing methods.
Table 1. Gene sequencing is the foundation and mainstream technology for genetic testing
Supply and demand **** together to drive the rapid development of gene sequencing
Sequencing cost and sequencing time consuming exponentially
The cost and time consuming of sequencing have been decreasing exponentially. With the continuous innovation of Next Generation Sequencing (NGS), the cost of determining a person's whole genome data has rapidly dropped from hundreds of millions of dollars to $1,000 at present, and the sequencing time has also dropped to 3 days.
Primary stage of human genome data accumulation completed
After more than 10 years of accumulation, the human genome database has taken initial shape, and in 2003, the Human Genome Project (HGP), a 13-year, $3 billion project by scientists from the United States and six other countries, was announced as complete. In 2003, the Human Genome Project (HGP), a 13-year, $3 billion project by scientists from six countries, including the United States, was announced as complete. In the same year, the "Encyclopedia of DNA Elements Project" was launched, and the research results were publicly released in 2012, which had a significant impact on the research of gene sequences related to human diseases. Subsequently, the International Thousand Genomes Project, the UK 100,000 Genomes Project, and the US Million Genomes Project were launched in 2008, 2014 and 2015, respectively. These programs have provided a solid foundation for the accumulation of human genome samples and the exploration of the relationship between diseases and genes.
Figure 7. Accumulation of human genome data has been completed, and major projects are accelerating
Genome data analysis methods have emerged
The analysis of the human genome has been initially streamlined and standardized. After nearly 30 years of development since it was first proposed in 1987, bioinformatics, from the initial collection and storage of genomic data, to the use of mathematical modeling and artificial intelligence ideas, mining the biological significance behind the data, reasonable classification of sample data, the establishment of reasonable secondary and tertiary databases, and then to the use of comparative genomics through short-reading sequence splicing, gene prediction and functional annotation. There has been a certain capability for handling large and complex genomic data.
Figure 8. Schematic diagram of the process of bioinformatics analysis of the human genome
Disease prevention and personalized treatment needs are far from being met
Modern science has confirmed that most diseases are the result of genes and the external environment *** with the same action, and the occurrence of almost all diseases (except injuries) are related to genes. Human genome research results show that the vast majority of the population carries certain classes of disease susceptibility genes, when the population is exposed to certain undesirable factors and the environment, its incidence is much higher than non-carrying susceptible genes population. Therefore, people are gradually realizing that only by truly understanding their own genes can they delay or prevent the occurrence of diseases as much as possible by improving the objective environment and having regular medical checkups.
China's rapid growth in the number of chronic disease patients has created an urgent need for precision medicine. Driving the demand for precision medicine. At present, there are 3.1 million new cases of cancer in China every year, 260 million patients with hypertension, more than 100 million people with diabetes, and 150 million potential diabetic patients; 2.2 million cancer deaths and 3 million cardiovascular disease deaths every year. The above diseases are difficult to be eradicated or cured through traditional methods, and there is an urgent need for precision medicine.
Table 2. Predicted number of chronic diseases in China's elderly population (10,000 people)
More and more people are realizing the importance of genetic sequencing for their own health. steven Jobs, the founder of Apple, who passed away in 2011, had his whole genome sequenced when he was suffering from cancer. in May 2013, Oscar-winning actress Angelina Jolie had her risk of breast cancer reduced from 87% to 20% by using a genetic test and the appropriate excision surgery. her breast cancer risk from 87 percent to 5 percent.
Gene sequencing market is expected to maintain an annual growth rate of more than 20%
The growth rate of the precision medicine market will far exceed that of the pharmaceutical industry as a whole. According to BCC Research, the global precision medicine market size of nearly 60 billion U.S. dollars in 2015, the annual growth rate is expected to be 15% in the next five years, which is three to four times the overall growth rate of the pharmaceutical industry. Among them, the global gene sequencing market size grew from $8 million in 2007 to about $4.5 billion in 2013, and is expected to maintain a growth rate of more than 20% in the next few years, to reach about $11.7 billion in 2018. markets and markets predicts that China's gene sequencing industry is expected to reach a CAGR of 20%-25% during the period of 2012-2017.