Screening And Bioinformatics Analysis Of Differentially Expressed Genes In Sleep Deprivation

Sleep occupy about one-third of our life, and sleep is closely related to the each individual’s physical and mental. And sleep is a physiological process of fine-tuning under the central nervous system. For nearly a century, sleep has aroused great interest of many scholars, and they are committed to research in this field. Although the physiological function and mechanism of sleep is still not very clear, but the important of sleep has long been a consensus for everyone. People can hunger strike himself, but they can not refused to sleep for a long time. Sleep deprivation or lack of sleep is a common social phenomenon, the negative impact it brings to people being more and more attention.The amount of sleep is not normal and abnormal sleep behavior occurs, it usually indicates a normal rhythm of sleep and wakefulness disorders appear alternately. Sleep disorders can be caused by many factors, and often associated with physical diseases, including sleep disorders and different states of sleep. Sleep and human health are closely related. Survey shows that many people are suffering from sleep disorders and sleep-related aspects of the disease, and the proportion of sleep disorders in adults up to 30%. In addition, according to China’s market research shows that six cities, the prevalence of insomnia within a year up to 57% of adults. Experts point out that sleep is extremely important to maintain the physiological functions of human life, and it is essential to the human body. Long-term insomnia can lead to brain dysfunction, a variety of harm to the body, seriously affecting the physical and mental health. At present, a lot of researches found that sleep deprivation can affect the expression of certain genes, inhibit inflammation-related factors neurogenesis, and may lead to diabetes, decreased sleep has also increased the risk of depression. For decades, although the adverse effects on human deprivation of sleep have a better understanding, but its mechanism of action remains unclear. In order to better prevention and treatment of sleep deprivation-related diseases, we need to reveal its pathogenesis at the molecular level.With the rapid development of the life sciences and the gradual implementation of the Human Genome Project, more and more animals and plants’ microbial genome sequence to be determined, the gene sequence data is growing rapidly at an unprecedented rate. Therefore, how to study the lives of so many genes in the process of gene function has become the world’s commitment to the life science workers common problems. For this reason, to establish a new hybrid method for sequencing large amounts of genetic information for efficient, rapid detection and analysis which is becoming very important. Microarray technology is the product of this scientific development conform to the requirements, it appears to solve such problems, and guided the direction and provide a bright future. Since microarray technology at the same time make a large number of probes immobilized on a support, so you can sample a large number of one-time sequence detection and analysis, so as to solve the complexity of traditional nucleic acid blotting techniques, low degree of automation, a small number of the sequence of operations, the detection efficiency low enough. Moreover, by designing a specific probe arrays and using a different analytical approach allows the technology has a variety of different value, such as gene expression profiles determined, mutation detection, DNA polymorphism analysis, genome mapping and sequencing by hybridization library and so on.A gene in RNA levels in different areas under ambient pressure, time, space, etc., the expression of genes significant difference is commonly referred to differentially expressed genes.The human genome is like telling a form each human cell DNA of the 3 billion base pairs arranged in precise "map." Scientists believe that by measuring the differential expression of each gene in the disease, people will be able to find new ways to treat and prevent many diseases, such as cancer and heart disease. Most gene expression in the biochip for the purpose of identifying the genes regulated by changing the conditions. The main purpose of such experiments is to identify genes differentially expressed under different conditions.Protein is not only the executor of life functions, but also directly reflected the phenomenon of life. Through the study of protein structure and function will directly reveal the mechanisms of life in the physiological or pathological conditions. And the protein function is often manifested in the interaction between protein and protein or protein and other biological macromolecules. The interaction of proteins is the direct embodiment of its function. Cell life activities is the physiological results of protein interactions in a certain time and space.Through the establishment of the network in model cell system by all protein interactions, and then it will establish a framework to study other functions of the proteins and global characteristics of the cell proteins. The destruction and change of the protein interactions network, often lead to cell dysfunction. Therefore, through the establishment of protein interaction networks and dynamic model for the study of protein interaction network. This will help to find the suitable drug targets, and provide a solid theoretical foundation for the development of new drugs.In recent years, the advanced technology for the analysis of protein-protein interactions including the yeast two hybrid system, fluorescence resonance energy transfer technology, the technology of surface plasmon resonance and protein chip technology. But in recent years, with the rapid development of bioinformatics, more and more researchers began using bioinformatics methods to study the interaction of the proteins.After ten years of rapid development, bioinformatics has entered the post genome era. The research area of bioinformatics is no longer confined to the efficient analysis of genomic and proteomic data, but transferred to the comparative genomics, metabolic network analysis, network analysis, spectrum of protein structure and function analysis and drug target screening, gene expression. At present, the research of bioinformatics and functional genomics has respectively, proteomics, genomic structure, and cooperate with each other closely related, is the hotspot of research in systems biology research at present.When the biologists going to reveal the phenomenon of life, they usually choose a species as a model organism, including growth characteristics, some of their gene sequence and function. Model organisms can not be replaced by experiment in scientific research, is due to a variety of biological activities of many basic life on earth are usually conservative. According to the scientific problems that researchers want to solve,so determine what kind of model organism we chose. And then choose some suitable experiment for this mode organism. Decades of research and development, people have found that the problem of developmental phenomena can usually be resolved by the relatively simple biological research. Because of the relatively simple organisms tend to be related to the operation of the observation and experiment. Therefore, research on Strategy of model organisms can be used not only in the scientific research in genetics, also can be widely used in developmental biology. After decades of scientific research and the accumulation of experience, has summed up some typical model organisms, including worms, fruit flies, Xenopus laevis, salamanders, mice. With the completion of human genome project and the arrival of the era of genomics research, model organism to study strategy to get more attention. The structure and function of genes can be studied in other species, the same physiological and pathological process of human can also select the appropriate organisms to simulation.On the taxonomy, mouse belonging Mammalia, rodents, murine, Mus animals. Mice are evolved by Mus musculus, they are widely distributed around the world. Mouse usually are selected as an ideal experimental animal. Due to the long-term breeding and selection of artificial cultivation, the major laboratories and Biotech Corp has bred more than 1000 inbred and outbred independent. Mice as early as seventeenth Century were chosen as the research object. Early in the 17th century, some people engaged in scientific research with mice. Mouse has now become the largest, most comprehensive study of mammalian animals. Drosophila melanogaster plays a very important role in twentieth Century of the development of the life science history. Drosophila as a model organism, has been very active, especially in the study of gene regulation and development of genetics. In addition, all kinds of neural disease, dementia, Parkinson’s disease, alcoholism and drug addiction are often use Drosophila as the research object. Drosophila as a model organism for the modeling and Simulation of biological characteristics of human body. Aging and longevity, learning and memory and cognitive behavior also gradually began to use Drosophila as a model organism to the scientific research. This study is divided into two parts: Part I:The effects and bioinformatics analysis of sleep deprivation on the expression of hippocampal genes in miceIn this study, we use firstly Qlucore Omics Explorer 3.0 software to analysis and screening for differentially expressed genes of microarray data GSE33302. GSE33302 chip data submitted by Peixoto L, etc.,which using a commercial ion channel chip platform of GPL 1261. The data include nine samples from sleep deprivation in the hippocampus of mice and the control group data from eight non-sleep-deprived mice hippocampus. We screened out 101 differentially expressed genes, including 66 down-regulated genes and 35 up-regulated genes from the data GSE33302.The use of PANTHER and DAVID two kinds of bioinformatics tools for comprehensive analysis of differentially expressed genes. We found that in the biological pathway, differentially expression genes were mainly involved in gonadotropin-releasing hormone receptor pathway, adrenaline and noradrenaline biosynthsis, inflammation mediated by chemokine and cytokine signaling pathway, apoptosis signaling pathway, huntington disease and parkinson disease and so on. In the biological process, wo fond that differentially expressed genes were mainly involved in the metabolic process, biological regulation process, development process, cellular localization process, the immune system and apoptosis process and so on.Finally, the software STRING is used to construct the protein-protein interaction network of genes in the data set of GSE33302 screened by QOE. Through the analysis and calculation of the protein-protein interaction network, in the data set of 101 genes screened in GSE33302, Usp2, Armtl, Dbp, Perl, Per2, Cryl, Cry2, Clock, Mapkl, Prkagl, Prkag2, Prkag3, Prkaal, Prkaa2, Prkab2, Eprs, Rars, Xpo1, Upf3b, Notchl, Rael, Apoe, Apob, Apoal, Lipc, Hspa5, Sin3a, Hdacl, Jun are interact with other more than 5 protein, which are the central node for the protein interaction network, the core protein. Remove the node of the network, the structure of protein will collapse. Therefore, these proteins may play an important role in the occurrence and development of diseases associated with sleep deprivation.Part II:The effects and bioinformatics analysis of sleep deprivation on the expression of the Drosophila brain geneIn this study, firstly Qlucore Omics Explorer 3.0 software is used to analysis the microarray data GSE4174 for differentially expressed genes. The data GSE4174 was submited by Zimmerman et, it is using commercial ion channel chip platform GPL72, which include nine samples of sleep deprivation in Drosophila brain tissue, and the control group data of six non-sleep-deprived brain tissue of Drosophila. Data was analysis by QOE.And then we screened out 171 differentially expressed genes, which 125 genes was down-regulated, and 46 genes were up-regulated.By Panther biological pathway analysis we found that differentially expressed genes involved a total of 20 biological pathways, which mainly involve thiamine metabolic pathways, Notch signaling pathway, transcriptional regulatory pathways, dopamine receptor signaling pathways regulating, Wnt signaling pathway, Ras pathway, pyruvate metabolic pathway, de novo purine synthesis pathway and other pathways and DNA replication. Panther biological process analysis showed that major differences genes are involved in the biosynthesis of the cell composition, cellular processes, cellular localization process, the process of apoptosis, biological adjustment process, reaction to stimuli, during the development of multicellular organization process, biological linking process, metabolism and immune system processes. Panther molecular function analysis showed that differentially expressed genes mainly related transporter activity, protein binding transcription factor activity, modulates the activity of the enzyme, catalytic activity, receptor activity, nucleic acid-binding transcription factor activity, antioxidant activity and the structure of the active molecule, such as binding activity. Panther cell component analysis showed that the differentially expressed genes including cell component of cell membranes, organelles and macromolecular complexes and so on.Finally, the software STRING is used to construct the protein-protein interaction network of genes in the data set of GSE4174 screened by QOE. Through the analysis and calculation of the protein interaction network diagram, in the data set of 171 genes screened in GSE4174, BRM, DDB1, Ssll, His3.3A, Spt5, Cyck, Hsp83, CG1646, CG6015, CG8258, CG5525, CG1416 and CGtgamma are interact with other more than 5 protein in the interaction, which are the center genes of this protein interaction network node. Remove the node in the network,we find that the structure of protein is collapsed. Therefore, these proteins may play an important role in the occurrence and development of diseases associated with sleep deprivation.