Key Laboratory of Intelligent Computing & Information Processing (Xiangtan University), Ministry of Education, China, Xiangtan, 411105, Hunan, People's Republic of China.
College of Information Engineering, Xiangtan University, Xiangtan, Hunan, People's Republic of China.
BMC Bioinformatics. 2018 Apr 17;19(1):141. doi: 10.1186/s12859-018-2146-x.
Recently, numerous laboratory studies have indicated that many microRNAs (miRNAs) are involved in and associated with human diseases and can serve as potential biomarkers and drug targets. Therefore, developing effective computational models for the prediction of novel associations between diseases and miRNAs could be beneficial for achieving an understanding of disease mechanisms at the miRNA level and the interactions between diseases and miRNAs at the disease level. Thus far, only a few miRNA-disease association pairs are known, and models analyzing miRNA-disease associations based on lncRNA are limited.
In this study, a new computational method based on a distance correlation set is developed to predict miRNA-disease associations (DCSMDA) by integrating known lncRNA-disease associations, known miRNA-lncRNA associations, disease semantic similarity, and various lncRNA and disease similarity measures. The novelty of DCSMDA is due to the construction of a miRNA-lncRNA-disease network, which reveals that DCSMDA can be applied to predict potential lncRNA-disease associations without requiring any known miRNA-disease associations. Although the implementation of DCSMDA does not require known disease-miRNA associations, the area under curve is 0.8155 in the leave-one-out cross validation. Furthermore, DCSMDA was implemented in case studies of prostatic neoplasms, lung neoplasms and leukaemia, and of the top 10 predicted associations, 10, 9 and 9 associations, respectively, were separately verified in other independent studies and biological experimental studies. In addition, 10 of the 10 (100%) associations predicted by DCSMDA were supported by recent bioinformatical studies.
According to the simulation results, DCSMDA can be a great addition to the biomedical research field.
最近,许多实验室研究表明,许多 microRNAs(miRNAs)参与并与人类疾病相关,可作为潜在的生物标志物和药物靶点。因此,开发有效的计算模型来预测疾病和 miRNAs 之间的新关联,有助于从 miRNA 水平理解疾病机制,以及从疾病水平理解疾病和 miRNAs 之间的相互作用。迄今为止,仅已知少数 miRNA-疾病关联对,且基于 lncRNA 分析 miRNA-疾病关联的模型有限。
在这项研究中,我们开发了一种新的基于距离相关集的计算方法,通过整合已知的 lncRNA-疾病关联、已知的 miRNA-lncRNA 关联、疾病语义相似性以及各种 lncRNA 和疾病相似性度量,来预测 miRNA-疾病关联(DCSMDA)。DCSMDA 的新颖之处在于构建了一个 miRNA-lncRNA-疾病网络,该网络表明 DCSMDA 可用于预测潜在的 lncRNA-疾病关联,而无需任何已知的 miRNA-疾病关联。尽管 DCSMDA 的实现不需要已知的疾病-miRNA 关联,但在留一交叉验证中,曲线下面积为 0.8155。此外,我们在前列腺肿瘤、肺癌和白血病的案例研究中实施了 DCSMDA,在这三个案例中,分别有 10、9 和 9 个预测关联在其他独立研究和生物实验研究中得到了验证。此外,DCSMDA 预测的 10 个关联中有 10 个(100%)得到了最近生物信息学研究的支持。
根据模拟结果,DCSMDA 可以为生物医学研究领域带来很大的帮助。