Bioinformatics Analysis Of Tacrolimus And Its Potential Therapeutic Significance For Autism Spectrum Disorders

Objective:Autism Spectrum Disorder(ASD)is a generic term for a group of neurodevelopmental disorders characterized by deviating from normal performance in social interaction,language communication,and interest behavior.Currently,there is no specific treatment method for ASD.Finding drugs that can be used to treat ASD among the discovered drugs is a feasible method.According to the “drug-target” association prediction study of ASD constructed by the research team in the early stage,tacrolimus has a potential therapeutic effect on ASD.This study is based on bioinformatics methods to analyze the potential association between tacrolimus and ASD,with a view to providing reference for the clinical treatment of ASD.Methods:Obtain the gene expression profile data of tacrolimus and ASD from the Gene Expression Omnibus(GEO)database,calculate the differentially expressed genes(DEGs)of tacrolimus and ASD,construct a Protein Protein Interaction(PPI)network with tacrolimus DEGs as the object,and screen out the key genes in the PPI network,and conducted gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the DEGs of tacrolimus and ASD,compared the DEGs and pathways of tacrolimus and ASD,analyzed the relationship between the two,and calculated the drugs and diseases associated with tacrolimus using drug-disease association platforms.Finally,the association between the key genes of tacrolimus and ASD was textual verified using the domain knowledge scoring method.Results:Through bioinformatics analysis,398 DEGs of tacrolimus were selected,among which GO enriched genes were mostly involved in the processes of energy cycle,Wnt signalosome,MAP kinase activity,etc.KEGG enriched genes are mainly involved to the pathway of MAPK signaling pathway,m TOR signaling pathway,Tricarboxylic Acid cycle(TCA cycle),etc.In the PPI network,a total of 396 proteins were obtained,and 10 key genes were calculated.There are 1797 DEGs in ASD,of which KEGG enriched genes are mainly involved in the complement and coagulation cascade,JAK-STAT signaling pathway,AMPK signaling pathway,and citrate cycle(TCA cycle),and other pathways.Through the Multi-source data drug-repositioning platform,CTD and the HERB database,it was found that tacrolimus has a complex impact on the body.Through text mining,a total of 21 documents related to the role of ASD and key targets of tacrolimus were retrieved,verifying the effectiveness of key targets.Conclusion:Based on the drug-disease association analysis of the Multi-source data drug-repositioning platform,CTD and HERB database,it was found that tacrolimus has therapeutic effects on diseases such as membranous nephropathy,has a potential therapeutic effects on mental disorders such as ASD,and has potential synergistic effects with drugs such as dexamethasone,resveratrol,and Human Placenta.Tacrolimus has regulatory effects on processes or pathways such as immune response and inflammatory response,it may not only inhibit immune response,but also have the function of inhibiting neuroinflammation,which has potential therapeutic significance for ASD patients.