Construction And Research Of Male Infertility And Prostate Cancer System Medical Information Platform

Background:System medicine is an interdisciplinary subject of system biology and modern medicine.Through the integration and analysis of massive and complex medical data,resources and information,it expounds the expression regulation mechanism of gene participation and achieves the purpose of guiding personalized treatment.The construction of systematic medical platform is mainly embodied in the construction of knowledge base and database.Generally,the knowledge base takes the disease as the center and the gene as the bridge to correlate and integrate the relevant genetic information,omics information and clinical information of the disease.Taking diseases as the main line,the database classifies and extracts the multi-group data and annotations of related diseases,and establishes the association network of genes and phenotypes,thus forming the multi-group library for diseases.This study,which focuses on two common male diseases,male sterility(MI)and prostate cancer(PCa),to state the research of both knowledgebase and database in systematic medicine.Male infertility refers to the inability of normal women to conceive due to male factors.Men account for 30-55%of the estimated 200 million infertile people worldwide,mostly in developing countries.The direct cause of male infertility is sperm defects,which lead to sperm abnormalities and quality deterioration in semen,and ultimately infertility,of which genetic factors account for about 30 percent.At present,some knowledge bases(such as SpermatogenesisOnline)have established the association between genetic factors and male sterility and spermatogenesis and have been widely recognized,but they do not highlight the relationship between gene mutations and male infertility phenotypes and some have stopped updating.In recent years,with the wide application of high-throughput sequencing technology in male infertility research,a large number of gene and clinical phenotype data have been published.However,these data are relatively scattered and not effectively utilized.Therefore,it is important to integrate existing data and establish a comprehensive knowledge base of gene-phenotypic male infertility.Prostate cancer is a malignant epithelial tumor that occurs in the prostate gland and is unique to men.It is the second most common cancer in men after lung cancer and kills more than 300,000 people worldwide each year.At present,although the diagnosis and treatment of prostate cancer has improved considerably,and genomics research has also made rapid progress,a huge number of various technical platform of omics data were produced at the same time.Some prostate cancer gene expression profile datasets and related tools developed by researchers are dispersed and independent,lacking a platform of prostate cancer to integrating multiple omics data and routine analysis tools.Objective:This present research takes male infertility and prostate cancer as examples to construct the knowledge base and database respectively to illustrate the application of systematic medicine in modern medicine.The male infertility Knowledge Base(MIgene)correlates gene pathogenicity locus with phenotypic information,which can provide early warning of disease risk and assist clinicians in timely diagnosis.Prostate cancer database(PCIP)helps to customize personalized treatment measures for prostate cancer according to tumor heterogeneity among different samples by establishing a gene-oriented multi-group data integration and analysis platform.Methods:MIgene:firstly the related literatures of male infertility and spermatogenesis were searched in the PubMed and Medline databases;Secondly,these papers were downloaded,abstracted,proofread,standardized,replenished and verified using manual and bioinformatic methods according to the reference databases;Finally,the data of genes and phenotypes were correlated,analyzed and visualized.PCIP:the datasets of prostate cancer were abstracted and preprocessed from the public databases such as TCGA,GEO and cBioPortal,which included genome,transcription,copy number variation,microRNA,and clinical information,etc.MIgene and PCIP were visualized by LAMP technologies.And the workflow analysis and environment configuration of PCIP were used by the Galaxy and Docker technologies.Results:MIgene was a web-accessible data repository about the genetic factors and clinical phenotypes of male infertility including a total of 664 genes,3606 mutants and 68(standard)phenotypes(classified into 37 categories)obtaining from 7985 studies in 989 papers,which offered four search moles and six modules covering the genes,phenotypes,proteins,functions,homologous and cases.PCIP was a gene-oriented database and collected 61 datasets,10,648 patients,and 14,134 samples for prostate cancer,which provided 7 major modules analyses in different subgroups.Conclusion:(1)MIgene(http://midb.geneworks.cn),the first global knowledge base for male infertility associated with genes and phenotypes,was successfully constructed.Friendly user interface and simple way of searching,easy for users to browse and download at any time.(2)PCIP(http://pcip.bio-it.cn),the successful build gene-oriented prostate cancer database,can carry on the multiple omics analysis to the samples of different subtype of prostate cancer samples,which for the first time to join the tumor infiltration and ScRNA-Seq analysis.(3)In the construction and research of knowledge base and database platform for diseases,systematic medicine makes precision medicine possible.