不同基因的蛋白质产物位于不同的亚细胞区室中。蛋白质定位的多样性可以作为基因特征,从亚细胞角度揭示基因的重要性。为了衡量这种多样性,我们引入了基于基因本体-细胞成分本体(GO-CCO)的亚细胞多样性指数(SDI)和GO术语的语义相似性度量。分析表明,人类基因的SDI与一些已知的基因重要性指标密切相关,包括蛋白质-蛋白质相互作用(PPI)网络拓扑测量,dN/dS比,同源基因编号,表达水平和组织特异性。此外,SDI在预测人类必需基因(AUC=0.702)和药物靶基因(AUC=0.704)方面具有良好的性能,SDI评分较高的药物靶标往往会引起更多的副作用。结果表明,SDI可用于识别新的药物靶标,并指导药物靶标的过滤,潜在的副作用较少。最后,我们开发了一个用户友好的在线数据库,用于查询8个物种的基因的SDI得分,以及基于SDI的人类药物靶标的预测概率。SDI的在线数据库可在以下网址获得:http://www。cuilab.cn/sdi.
Different genes have their protein products localized in various subcellular compartments. The diversity in protein localization may serve as a gene characteristic, revealing gene essentiality from a subcellular perspective. To measure this diversity, we introduced a Subcellular Diversity Index (SDI) based on the Gene Ontology-Cellular Component Ontology (GO-CCO) and a semantic similarity measure of GO terms. Analyses revealed that SDI of human genes was well correlated with some known measures of gene essentiality, including protein-protein interaction (PPI) network topology measurements, dN/dS ratio, homologous gene number, expression level and tissue specificity. In addition, SDI had a good performance in predicting human essential genes (AUC = 0.702) and drug target genes (AUC = 0.704), and drug targets with higher SDI scores tended to cause more side-effects. The results suggest that SDI could be used to identify novel drug targets and to guide the filtering of drug targets with fewer potential side effects. Finally, we developed a user-friendly online database for querying SDI score for genes across eight species, and the predicted probabilities of human drug target based on SDI. The online database of SDI is available at: http://www.cuilab.cn/sdi.