Correlation Analysis Between Gene-Gut Flora Based On Text Mining And Verifycation Through GRID2 Knock-Down

Objective : As a complex organ ecosystem,intestinal flora plays an important role in host health.At present,the number of researches on intestinal flora has been increased exponentially.The development trend in this field lacks a systematic and comprehensive analysis.in order to comprehensively analyze the research hotspots and development trends in the field of intestinal flora,bibliometric analysis of literature related to intestinal flora.Although many databases about gut microbiota have been reported,none of previously described databases can systematically explain the relationship among intestinal microbiota and disease and genes in various species,and provide users with a visual interface for easy retrieval and then aimed to establish a systematic and comprehensive intestinal flora and disease.Methods:1.Bibliometrics method: Based on the web of science database,keywords were set as: microbiome OR microbiota OR probiotic OR prebiotic OR metabolome.The analysis software of web of science and citespace software were used to conduct a comprehensive cluster visualization analysis of published literatures of intestinal flora.The time was ranged from 1994 to 2017.2.Database construction method:(1)based on Pubmed database and using large-scale text mining technology,the same keyword mentioned above is firstly used for search,and the time span is up to April 11,2017.(2)Reading the abstract of the literature and filtering out the main research articles in the sea,soil,plants and microorganisms,we recorded pubmed ID,microorganism,disease and other related information into Excel.(3)After two people's verification and comparison,we finally got the data to construct the database.(4)We import the filtered data into the Navicatfor My SQL database,and then use Dreamweaver8 and phpstudy to complete the front-end visualization.3.GRID2 function verification:(1)21 mice were randomly selected and divided into 2groups,10 wild type and 11 heterozygous.(2)Using the method of forcing,we collected the feces of 21 mice.(3)The stool samples were subjected to 16 s sequencing and bioinformatics analysis.Results: 1.Bibliometric results:(1)The number of articles published in the field of intestinal flora increased year by year.The country with the most publications is the United States,followed by China.(2)Microbiology,food technology,biotechnology microbiology,gastroenterology and hepatology are the main research directions in this field.(3)Researchers focus mainly on the probiotics,disease,expression and other aspects.2.Database result: Through text mining,we finally screened out 7233 related records.The database IMDGase of intestinal microflora,disease and gene of multiple species was constructed.The database contains 1,713 microbes,1,071 diseases,592 genes and 29 cancers,as well as 179 samples of different microbial origins and 32 species.The database also includes information such as publications,citations,et al.Users can search by search terms.Through the analysis of the database,we found that there is a correlation between intestinal flora-disease-genes.The relationship analysis among intestinal flora,disease and genes revealed that Firmicutes and Lactobacillus rhamnosus GG were associated with many diseases such as inflammatory bowel disease and diabetes,mainly involving the expression of genes such as TNF-?.IL-10,IL-6,IFN?.ALDH2,and GRID2 are closely related to several diseases,such as cardiovascular diseases and diabetes,which mainly related to intestinal flora such as bacteroides.Through the construction of this database,it provides abundant resources for deepening the relationship among intestinal flora-disease-gene.3.GRID2 function verification results:(1)The statistical analysis of three indexes of chao1 index,Shannon diversity index and Simpson diversity index in Alpha analysis indicated that the species composition in the wild group and the heterozygous group was more uniform,and the species richness of the heterozygous group was greater than wild group.(2)The beta diversity analysis found that there were differences in species composition between the two groups at different levels.For example,at the level of the phylum,bacteroides is more distributed in the heterozygous group than in the wild group,while tenericutes is less distributed.At the level of the Order,actinomycetales and bacteroidales were more distributed in the heterozygous group than in the wild group.Bacteroides and actinomycetes are associated with diseases such as diabetes and irritable bowel syndrome.Then,this part of the results verifies the database results.(3)Species difference analysis results showed that there were17 different species at the species level.(4)The LEf Se analysis showed that the key flora in the wild group were clostridiaceae,clostridium,allobaculum,and so on.Representative species that had a greater influence on the heterozygous group were mycoplasma,sphingomonas,alphaproteobacteria and so on.(5)Functional analysis revealed that there were 8 differential functions(p<0.05).Compared with the wild group,caffeine metabolism(p=0.047),cell cycle mycobacteria(p=0.050),fluorobenzoic acid and degradation(p=0.044),renin-angiotensin system function(p=0.028)of the heterozygous group occupied a higher sequence,while the neuroactive ligand-receptor interaction(p=9.99e-4),D-arginine and D-ornithine metabolism(p=0.039),cam ligand(The p=0.043),complement and coagulation cascades(p=0.043)were relatively low in function.These functions play a role in diseases such as neurological diseases such as Parkinson's disease,diabetes,and cardiovascular diseases.Conclusion: 1.Bibliometric conclusion:(1)Although the number of publications in this field is increasing year by year,the quantity of literature published in high-impact journals is small,and the quality of papers needs to be improved.(2)The number of published literatures of China in this field is at the forefront,but there is still a certain gap compared with developed countries.2.Database conclusion:(1)IMDGase database can provide users with a visual interface for easy retrieval.(2)The relationship between intestinal flora-disease-genes can systemly mining from this database.3.GRID2 function verification conclusion:(1)The GRID2 affects the richness and composition of the mouse intestinal flora.(2)The GRID2 influences the function of the intestinal flora.For example,renin-angiotensin system and neuroactive ligand-receptor interactions were found significant difference in GRID2 wild and heterozygote.These conclusions validate the results of our database mining.