IEEE J Biomed Health Inform. 2019 Jan;23(1):427-436. doi: 10.1109/JBHI.2018.2814609. Epub 2018 Mar 9.
Predicting the miRNA-target interactions (MTIs) is a critical task for elucidating mechanistic roles of miRNAs in pathophysiology. However, most existing techniques have a higher false positive because the precise miRNA target mechanisms are poorly known. Considering that ensemble methods can take advantage of the complementary knowledge in different methods, we propose an alternative optimization framework, Inferring MiRNA Targets based on Restricted Boltzmann Machines (IMTRBM), to enhance the accuracy of previous prediction results. First, the proposed method directly constructs a weighted MTI network though the results predicted by individual methods and each miRNA target pair is weighted based on the frequency appearing in these results. Second, we transform the miRNA-target prediction problem into a complete bipartite graph model, named restricted Boltzmann machine, and utilize a practical learning procedure to train our model and make predictions. Our results show that the algorithm outperforms individual miRNA-target prediction approach in the number of validated miRNA targets at cutoffs of top list. Moreover, our framework can tolerate the decrease and increase of predicted MTIs and even discover new miRNA targets, which have been a challenge to predict for any individual methods. Finally, for the miRNAs that are not appearing in IMTRBM, we design a new method to supplement IMTRBM based on the intuition that similar miRNAs have similar functions, which also achieves a comparable result. The source code of IMTRBM is available at https://github.com/liuying201705/IMTRBM.
预测 miRNA 与靶标相互作用(miRNA-Target Interactions,MTIs)对于阐明 miRNA 在病理生理学中的机制作用至关重要。然而,由于精确的 miRNA 靶标机制知之甚少,大多数现有技术的假阳性率较高。考虑到集成方法可以利用不同方法中的互补知识,我们提出了一种替代的优化框架,即基于受限玻尔兹曼机的 miRNA 靶标推断(Inferring MiRNA Targets based on Restricted Boltzmann Machines,IMTRBM),以提高先前预测结果的准确性。首先,该方法通过个体方法的预测结果直接构建加权的 miRNA-TI 网络,并且每个 miRNA 靶标对的权重基于在这些结果中出现的频率进行加权。其次,我们将 miRNA-靶标预测问题转化为一个完整的二分图模型,称为受限玻尔兹曼机,并利用实际的学习过程来训练我们的模型并进行预测。我们的结果表明,该算法在截点为列表顶部时,在验证 miRNA 靶标的数量上优于个体 miRNA-靶标预测方法。此外,我们的框架可以容忍预测 MTIs 的减少和增加,甚至可以发现新的 miRNA 靶标,这对于任何个体方法来说都是一个挑战。最后,对于不在 IMTRBM 中的 miRNA,我们基于相似的 miRNA 具有相似功能的直觉设计了一种基于 IMTRBM 的新方法来进行补充,这也取得了可比的结果。IMTRBM 的源代码可在 https://github.com/liuying201705/IMTRBM 上获得。