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In silico prediction of potential miRNA‐disease association using an integrative bioinformatics approach based on kernel fusion

机译:使用基于核融合的综合生物信息学方法进行计算机模拟潜在的miRNA-疾病关联

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摘要

Accumulating experimental evidence has demonstrated that microRNAs (miRNAs) have a huge impact on numerous critical biological processes and they are associated with different complex human diseases. Nevertheless, the task to predict potential miRNAs related to diseases remains difficult. In this paper, we developed a Kernel Fusion‐based Regularized Least Squares for MiRNA‐Disease Association prediction model (KFRLSMDA), which applied kernel fusion technique to fuse similarity matrices and then utilized regularized least squares to predict potential miRNA‐disease associations. To prove the effectiveness of KFRLSMDA, we adopted leave‐one‐out cross‐validation (LOOCV) and 5‐fold cross‐validation and then compared KFRLSMDA with 10 previous computational models (MaxFlow, MiRAI, MIDP, RKNNMDA, MCMDA, HGIMDA, RLSMDA, HDMP, WBSMDA and RWRMDA). Outperforming other models, KFRLSMDA achieved AUCs of 0.9246 in global LOOCV, 0.8243 in local LOOCV and average AUC of 0.9175 ± 0.0008 in 5‐fold cross‐validation. In addition, respectively, 96%, 100% and 90% of the top 50 potential miRNAs for breast neoplasms, colon neoplasms and oesophageal neoplasms were confirmed by experimental discoveries. We also predicted potential miRNAs related to hepatocellular cancer by removing all known related miRNAs of this cancer and 98% of the top 50 potential miRNAs were verified. Furthermore, we predicted potential miRNAs related to lymphoma using the data set in the old version of the HMDD database and 80% of the top 50 potential miRNAs were confirmed. Therefore, it can be concluded that KFRLSMDA has reliable prediction performance.
机译:越来越多的实验证据表明,microRNA(miRNA)对许多关键的生物学过程具有巨大的影响,并且它们与不同的复杂人类疾病相关。然而,预测与疾病相关的潜在miRNA的任务仍然很困难。在本文中,我们为MiRNA疾病关联预测模型(KFRLSMDA)开发了基于核融合的正则化最小二乘法,该模型将核融合技术应用于融合相似性矩阵,然后利用正则化最小二乘来预测潜在的miRNA疾病关联。为了证明KFRLSMDA的有效性,我们采用了留一法交叉验证(LOOCV)和5倍交叉验证,然后将KFRLSMDA与10个先前的计算模型(MaxFlow,MiRAI,MIDP,RKNNMDA,MCMDA,HGIMDA,RLSMDA)进行了比较,HDMP,WBSMDA和RWRMDA)。在5次交叉验证中,KFRLSMDA在全球LOOCV中的AUC为0.9246,在本地LOOCV中为0.8243,平均AUC为0.9175±0.0008,优于其他模型。此外,实验发现分别确认了前50种潜在的miRNA分别用于乳腺肿瘤,结肠肿瘤和食道肿瘤的96%,100%和90%。我们还通过去除所有已知的与肝细胞癌相关的miRNA来预测与肝细胞癌相关的潜在miRNA,并验证了前50种潜在miRNA中的98%。此外,我们使用旧版HMDD数据库中的数据集预测了与淋巴瘤相关的潜在miRNA,并确认了前50种潜在miRNA中的80%。因此,可以断定KFRLSMDA具有可靠的预测性能。

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