Discovery Of Novel Drug Targets In Basis Of Tissue-specific Expression

The tissue-specific genes are a group of genes whose function and expression are enriched in one tissue type.Many previous studies have found that tissue-specific genes are highly correlated with disease;and disease-associated genes tend to be located in the tissues where the disease occurs.Therefore,identification of the tissue-enriched genes helps better understanding of etiology and discovery of novel tissue-specific therapeutic targets.In this study,we developed a new tissue-specific score Tscore,as a complement to the specific measure SPM,for rapid identification of tissue-specific genes.To evaluated the method,we downloaded six Next-generation sequencing(RNA-seq)transcriptomes and four microarray transcriptomes from public resources,covering over 105 human tissues and 10,428 samples.By calculating the SPM and Tscore value,we identified 6,156 tissue-specific protein-coding genes and 19,100 tissue-specific non-coding genes.We further compared the genes identified by the new method with four well-known tissue-specific gene databases.The results proved the new method performed well in accurate detection of tissue-specific genes.Subsequently,we evaluated the tissue-specific gene expression at the protein level.By doing so,we detected 421 genes that were tissue-specific expression at both gene and protein levels.Furthermore,we derived disease-related information of these 421 genes from the DisGeNET database,and confirmed the focal sites via mapping the diseases against the MeSH database.Eventually,we identified 11 potential novel drug targets with literature verification.To sum up,the study introduces a new strategy for identifying tissue-specific genes as therapeutic targets.It will be useful to communities of ideology and pharmacology.