Prediction of CircRNA-Disease Associations Using KATZ Model Based on Heterogeneous Networks
Prediction of CircRNA-Disease Associations Using KATZ Model Based on Heterogeneous Networks
复制标题
使用基于异构网络的 KATZ 模型预测 CircRNA-疾病关联
DOI：
10.7150/ijbs.28260
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发表时间：
2018-01-01
影响因子：
9.2
通讯作者：
Wu, Fang-Xiang
中科院分区：
文献类型：
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作者：
Fan, Chunyan;Lei, Xiujuan;Wu, Fang-Xiang
环状rna （circRNAs）是一大类内源性非编码rna，是基因调控过程的关键成员。这些环状rna在人类健康和疾病中发挥着重要作用。由于其普遍性、特异性和稳定性的特点，circrna正成为疾病诊断、治疗和预后的理想生物标志物。确定circrna与疾病之间的关系有助于理解复杂的疾病机制。然而，传统的实验既昂贵又耗时，而且很少有计算模型被开发出来来预测新的环状rna与疾病的关联。在本研究中，利用circRNA表达谱、疾病表型相似性和高斯相互作用谱核相似性构建了一个异构网络。然后，我们开发了用于人类circrna -疾病关联预测（KATZHCDA）的KATZ测量计算模型。采用留一交叉验证（LOOCV）和五重交叉验证来研究这四种相似性度量的效果。因此，KATZHCDA模型在LOOCV和5倍交叉验证中的auc分别为0.8469和0.7936+/-0.0065。进一步，我们分析了hsa_circ_0006054与结直肠癌的候选相关性，结果表明hsa_circ_0006054可能在结直肠癌的癌变过程中起到miRNA海绵的作用。综上所述，我们的模型有望成为临床实验指导的有效资源。
Circular RNAs (circRNAs) are a large group of endogenous non-coding RNAs which are key members of gene regulatory processes. Those circRNAs in human paly significant roles in health and diseases. Owing to the characteristics of their universality, specificity and stability, circRNAs are becoming an ideal class of biomarkers for disease diagnosis, treatment and prognosis. Identification of the relationships between circRNAs and diseases can help understand the complex disease mechanism. However, traditional experiments are costly and time-consuming, and little computational models have been developed to predict novel circRNA-disease associations. In this study, a heterogeneous network was constructed by employing the circRNA expression profiles, disease phenotype similarity and Gaussian interaction profile kernel similarity. Then, we developed a computational model of KATZ measures for human circRNA-disease association prediction (KATZHCDA). The leave-one-out cross validation (LOOCV) and 5-fold cross validation were implemented to investigate the effects of these four types of similarity measures. As a result, KATZHCDA model yields the AUCs of 0.8469 and 0.7936+/-0.0065 in LOOCV and 5-fold cross validation, respectively. Furthermore, we analyze the candidate association between hsa_circ_0006054 and colorectal cancer, and results showed that hsa_circ_0006054 may function as miRNA sponge in the carcinogenesis of colorectal cancer. Overall, it is anticipated that our proposed model could become an effective resource for clinical experimental guidance.