Construction Of The Molecular Characteristic Database Of Alzheimer’s Disease Brain Based On Single Cell Transcriptome

Background: Alzheimer’s disease(AD)is a highly heterogeneous.Single cell RNA sequencing(sc RNA-seq)is effective in explaining the cellular heterogeneity of AD.A wealth of valuable AD brain sc RNA-seq data has been generated over the past decade,but studies integrating these multi-source data are rare,greatly limiting the repurposing of these publicly available data by non-bioinformatics scientist.Therefore,it is necessary to establish an analysis and visualization platform for AD brain sc RNAseq data.Objective: Based on the existing AD brain sc RNA-seq data(human and mouse),construct transcriptional profiles and databases,and provide a data analysis and visualization platform to assist experimental design and hypotheses verification.Furthermore,use the platform to analyze the association between the microglia functional changes and AD,and its potential mechanism.Methods: The sc RNA-seq datasets of AD brains were collected from the Gene Expression Omnibus(GEO)and Synapse databases,and the raw sequencing data and sample information were downloaded using the SRA,synapseclient,and synapseutils python packages.Raw sequencing data were processed using Cell Ranger and Seurat standard procedures to obtain a single-cell expression matrix.Data is analyzed and visualized using the R language.Use R Shiny to build a database platform.Results: We constructed a web-based platform called SCAD-Brain(sc RNA-seq of AD Brain,http://www.bioinform.cn/SCAD/),for AD sc RNA-seq data analysis,visualization,and mining SCAD-Brain includes the following functional modules: 1)Cell marker gene analysis;2)Comparative analysis between cell types;3)Difference analysis between AD and normal groups;4)Cell communication analysis;5)Cell trajectory analysis.Based on SCAD-Brain,the differences in the content of microglia,marker genes and cell communication between AD and normal people were further analyzed to analyze the relationship between the functional changes of microglia and AD.Conclusion:(1)We established SCAD-Brain,a database platform to provide the transcriptional molecular characteristics of AD brain tissue in single-cell resolution.(2)Based on SCAD-Brain,we found that the population,marker genes,and cellular communication of the activated homeostatic microglia were decreased in AD.In addition,RNASET2,SRGAP2,and LPAR6 genes may be potential new marker genes for microglia.