Integrated Analysis Of Orphan GPCR Function Based On Single Cell Expression Profile

G protein-coupled receptors(GPCRs)are the largest family of membrane integration receptors,which mediates most cell responses to environmental stimuli.Based on the extensive significance of GPCRs in human diseases and its pharmacological accessibility and controllability,GPCRs have become the most developed therapeutic target in modern medicine.With the continuous deepening of genome and proteome research,the number of data related to GPCR research is increasing.The construction of a concise,non-redundant,and highly specific database can provide clues for further studying the functions of GPCRs and further clarifying the mechanism of interaction between GPCR receptors and ligands.In recent years,many professional databases related to GPCRs have been developed at home and abroad,including protein sequence,modification,structure,signal pathway,single nucleotide polymorphism,mutation,disease-related and ligand information,among which GPCRDB,GRAP and gp DB are more representative.However,there are no studies on the analysis and construction of GPCR cell typespecific expression from the single cell level.The latest advances in biotechnology have provided a new way to study the biological role of GPCRs and the correlation between diseases.Single cell RNA sequence(sc RNA-seq)is a powerful technology to explore the transcriptome of a single cell in health and disease conditions.Compared with the traditional bulk RNA-seq,sc RNA-seq can characterize the transcriptome of a specific cell type with higher resolution.In view of this,this study started with a large number of published sc RNA-seq data sets of five species-human(Homo sapiens),mouse(Mus musculus),rat(Rattus norvegicus),macaca(Macaca fascicularis)and chimpanzee(Pan troglodytes),for collection,statistical analysis,annotation and visualization,to establish a comprehensive public database,G protein-coupled receptor single-cell expression profile(GPCR-SCEP),to provide the visualization of cell type-specific expression of GPCR at the single-cell level.In addition,with the completion of the Human Genome Project,the research of functional genomics shows that GPCRs are involved in various processes of life activities and the occurrence and development of diseases.GPCRs have become star targets for drug development.Orphan GPCRs are a group of GPCRs with unknown endogenous ligand and unknown function.At present,more than 100 GPCRs are regarded as orphan receptors.The study of these orphan GPCRs and their functions not only helps to understand the mechanism of cell signal transduction and clarify the pathogenesis of diseases,but also provides new ideas for drug research and development,which has important theoretical significance and application value.However,determining the ligand and function of GPCRs by traditional experimental methods is not only costly,but also difficult to adapt to the rapid growth of its protein sequence.Therefore,GPCR potential ligand analysis and function prediction based on computational methods is one of the effective ways to solve this problem.Based on different bioinformatics methods,this study predicted and analyzed the potential ligands and functions of orphan GPCRs.For potential ligand prediction,this study predicts potential ligands for orphan GPCRs by integrating information such as the receptor-ligand co-expression correlation between tumor cells and macrophages in the above single cell expression profile and binding scores derived from different protein interaction databases.For functional prediction,on the one hand,combining single cell transcriptome profiling with genome-wide association studies(GWAS)to jointly estimate related tissue/cell types and susceptibility genes for complex phenotypes,and ultimately revealing specific traits that orphan GPCRs may participate in through the association of orphan GPCRs with specific cell types and specific traits.On the other hand,data from gene perturbation experiments are analyzed to extract differentially expressed genes.Using the Cmap,a large gene perturbation database,genes with similar transcription characteristics after perturbation with orphan GPCRs are searched,indicating that orphan GPCRs have similar biological functions to these genes.