Abstract

BackgroundMiRNAs play significant roles in many fundamental and important biological processes, and predicting potential miRNA-disease associations makes contributions to understanding the molecular mechanism of human diseases. Existing state-of-the-art methods make use of miRNA-target associations, miRNA-family associations, miRNA functional similarity, disease semantic similarity and known miRNA-disease associations, but the known miRNA-disease associations are not well exploited.ResultsIn this paper, a network embedding-based multiple information integration method (NEMII) is proposed for the miRNA-disease association prediction. First, known miRNA-disease associations are formulated as a bipartite network, and the network embedding method Structural Deep Network Embedding (SDNE) is adopted to learn embeddings of nodes in the bipartite network. Second, the embedding representations of miRNAs and diseases are combined with biological features about miRNAs and diseases (miRNA-family associations and disease semantic similarities) to represent miRNA-disease pairs. Third, the prediction models are constructed based on the miRNA-disease pairs by using the random forest. In computational experiments, NEMII achieves high-accuracy performances and outperforms other state-of-the-art methods: GRNMF, NTSMDA and PBMDA. The usefulness of NEMII is further validated by case studies. The studies demonstrate the great potential of network embedding method for the miRNA-disease association prediction, and SDNE outperforms other popular network embedding methods: DeepWalk, High-Order Proximity preserved Embedding (HOPE) and Laplacian Eigenmaps (LE).ConclusionWe propose a new method, named NEMII, for predicting miRNA-disease associations, which has great potential to benefit the field of miRNA-disease association prediction.

Highlights

  • MiRNAs play significant roles in many fundamental and important biological processes, and predicting potential miRNA-disease associations makes contributions to understanding the molecular mechanism of human diseases

  • Known miRNA-disease associations are formulated as a bipartite network, and the network embedding method Structural Deep Network Embedding (SDNE) is adopted to learn node embeddings in the bipartite network

  • network embedding-based multiple information integration method (NEMII) achieves high-accuracy performances and outperforms other state-of-the-art methods: GRNMF, NTSMDA and PBMDA

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Summary

Introduction

MiRNAs play significant roles in many fundamental and important biological processes, and predicting potential miRNA-disease associations makes contributions to understanding the molecular mechanism of human diseases. MiRNAs are usually considered as negative gene regulators, which regulate the expression of messenger RNAs in a sequence-specific manner and repress the protein translation of their target genes. Two well-studied miRNAs: Let-7 and the synthetic miRNA miRcxcr induce translation upregulation of target messenger RNAs on cell cycle arrest [2]. The increasing evidence demonstrated that miRNAs play critical roles in important biological processes, such as cell growth [3], tissue differentiation [4], cell proliferation [5], embryonic development and apoptosis [6, 7]. The identification of miRNA-disease associations is significant for understanding the molecular mechanisms of human diseases and promoting the diagnosis and treatment of human diseases. Experimental determination of miRNA-disease associations is tremendously expensive and laborious, and has a

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