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基于半聚类的阿尔茨海默病相关 miRNA 识别

Identifying Alzheimer's Disease-related miRNA Based on Semi-clustering.

机构信息

Department of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.

Department of General Surgery, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, China.

出版信息

Curr Gene Ther. 2019;19(4):216-223. doi: 10.2174/1566523219666190924113737.

Abstract

BACKGROUND

More and more scholars are trying to use it as a specific biomarker for Alzheimer's Disease (AD) and mild cognitive impairment (MCI). Multiple studies have indicated that miRNAs are associated with poor axonal growth and loss of synaptic structures, both of which are early events in AD. The overall loss of miRNA may be associated with aging, increasing the incidence of AD, and may also be involved in the disease through some specific molecular mechanisms.

OBJECTIVE

Identifying Alzheimer's disease-related miRNA can help us find new drug targets, early diagnosis.

MATERIALS AND METHODS

We used genes as a bridge to connect AD and miRNAs. Firstly, proteinprotein interaction network is used to find more AD-related genes by known AD-related genes. Then, each miRNA's correlation with these genes is obtained by miRNA-gene interaction. Finally, each miRNA could get a feature vector representing its correlation with AD. Unlike other studies, we do not generate negative samples randomly with using classification method to identify AD-related miRNAs. Here we use a semi-clustering method 'one-class SVM'. AD-related miRNAs are considered as outliers and our aim is to identify the miRNAs that are similar to known AD-related miRNAs (outliers).

RESULTS AND CONCLUSION

We identified 257 novel AD-related miRNAs and compare our method with SVM which is applied by generating negative samples. The AUC of our method is much higher than SVM and we did case studies to prove that our results are reliable.

摘要

背景

越来越多的学者试图将其作为阿尔茨海默病(AD)和轻度认知障碍(MCI)的特定生物标志物。多项研究表明,miRNA 与轴突生长不良和突触结构丧失有关,这两者都是 AD 的早期事件。miRNA 的总体缺失可能与衰老有关,增加了 AD 的发病率,并且可能通过某些特定的分子机制参与疾病。

目的

鉴定与阿尔茨海默病相关的 miRNA 有助于我们找到新的药物靶点,进行早期诊断。

材料和方法

我们使用基因作为桥梁,通过已知的 AD 相关基因来寻找更多与 AD 相关的基因。然后,通过 miRNA-基因相互作用获得每个 miRNA 与这些基因的相关性。最后,每个 miRNA 都可以得到一个表示其与 AD 相关性的特征向量。与其他研究不同,我们没有使用分类方法通过随机生成负样本来识别与 AD 相关的 miRNAs。在这里,我们使用半聚类方法“单类 SVM”。与 AD 相关的 miRNAs 被视为异常值,我们的目标是识别与已知 AD 相关 miRNAs(异常值)相似的 miRNAs。

结果和结论

我们鉴定了 257 个新的与 AD 相关的 miRNAs,并将我们的方法与通过生成负样本应用的 SVM 进行了比较。我们的方法的 AUC 远高于 SVM,我们进行了案例研究以证明我们的结果是可靠的。

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