School of Mathematics and Statistics, Xi'an Jiaotong University, Xianning West 28, Xi'an, China.
BMC Genomics. 2020 Nov 18;21(Suppl 10):617. doi: 10.1186/s12864-020-07006-x.
Biological evidence has shown that microRNAs(miRNAs) are greatly implicated in various biological progresses involved in human diseases. The identification of miRNA-disease associations(MDAs) is beneficial to disease diagnosis as well as treatment. Due to the high costs of biological experiments, it attracts more and more attention to predict MDAs by computational approaches.
In this work, we propose a novel model MTFMDA for miRNA-disease association prediction by matrix tri-factorization, based on the known miRNA-disease associations, two types of miRNA similarities, and two types of disease similarities. The main idea of MTFMDA is to factorize the miRNA-disease association matrix to three matrices, a feature matrix for miRNAs, a feature matrix for diseases, and a low-rank relationship matrix. Our model incorporates the Laplacian regularizers which force the feature matrices to preserve the similarities of miRNAs or diseases. A novel algorithm is proposed to solve the optimization problem.
We evaluate our model by 5-fold cross validation by using known MDAs from HMDD V2.0 and show that our model could obtain the significantly highest AUCs among all the state-of-art methods. We further validate our method by applying it on colon and breast neoplasms in two different types of experiment settings. The new identified associated miRNAs for the two diseases could be verified by two other databases including dbDEMC and HMDD V3.0, which further shows the power of our proposed method.
生物证据表明,microRNAs(miRNAs)在涉及人类疾病的各种生物学进展中都有很大的牵连。miRNA-疾病关联(MDA)的鉴定有助于疾病的诊断和治疗。由于生物实验成本高昂,通过计算方法预测 MDA 越来越受到关注。
在这项工作中,我们提出了一种新的基于矩阵三因子化的模型 MTFMDA,用于 miRNA-疾病关联预测,该模型基于已知的 miRNA-疾病关联、两种 miRNA 相似性和两种疾病相似性。MTFDA 的主要思想是将 miRNA-疾病关联矩阵分解为三个矩阵,一个 miRNA 的特征矩阵,一个疾病的特征矩阵和一个低秩关系矩阵。我们的模型结合了拉普拉斯正则化,迫使特征矩阵保留 miRNA 或疾病的相似性。提出了一种新的算法来解决优化问题。
我们通过使用 HMDD V2.0 中的已知 MDA 进行 5 倍交叉验证来评估我们的模型,并表明我们的模型在所有最先进的方法中可以获得显著最高的 AUC。我们通过在两种不同的实验设置中应用于结肠和乳腺癌进一步验证了我们的方法。这两种疾病的新识别的相关 miRNA 可以通过另外两个数据库包括 dbDEMC 和 HMDD V3.0 进行验证,这进一步表明了我们提出的方法的有效性。