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      A network embedding-based multiple information integration method for the MiRNA-disease association prediction

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          Abstract

          Background

          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. 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.

          Results

          In 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).

          Conclusion

          We propose a new method, named NEMII, for predicting miRNA-disease associations, which has great potential to benefit the field of miRNA-disease association prediction.

          Electronic supplementary material

          The online version of this article (10.1186/s12859-019-3063-3) contains supplementary material, which is available to authorized users.

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          Most cited references36

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          Laplacian Eigenmaps for Dimensionality Reduction and Data Representation

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            Switching from repression to activation: microRNAs can up-regulate translation.

            AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
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              Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis

              Background Methylotrophic yeast species (e.g. Hansenula polymorpha, Pichia pastoris) can grow on methanol as sole source of carbon and energy. These organisms are important cell factories for the production of recombinant proteins, but are also used in fundamental research as model organisms to study peroxisome biology. During exponential growth on glucose, cells of H. polymorpha typically contain a single, small peroxisome that is redundant for growth while on methanol multiple, enlarged peroxisomes are present. These organelles are crucial to support growth on methanol, as they contain key enzymes of methanol metabolism. In this study, changes in the transcriptional profiles during adaptation of H. polymorpha cells from glucose- to methanol-containing media were investigated using DNA-microarray analyses. Results Two hours after the shift of cells from glucose to methanol nearly 20% (1184 genes) of the approximately 6000 annotated H. polymorpha genes were significantly upregulated with at least a two-fold differential expression. Highest upregulation (> 300-fold) was observed for the genes encoding the transcription factor Mpp1 and formate dehydrogenase, an enzyme of the methanol dissimilation pathway. Upregulated genes also included genes encoding other enzymes of methanol metabolism as well as of peroxisomal β-oxidation. A moderate increase in transcriptional levels (up to 4-fold) was observed for several PEX genes, which are involved in peroxisome biogenesis. Only PEX11 and PEX32 were higher upregulated. In addition, an increase was observed in expression of the several ATG genes, which encode proteins involved in autophagy and autophagy processes. The strongest upregulation was observed for ATG8 and ATG11. Approximately 20% (1246 genes) of the genes were downregulated. These included glycolytic genes as well as genes involved in transcription and translation. Conclusion Transcriptional profiling of H. polymorpha cells shifted from glucose to methanol showed the expected downregulation of glycolytic genes together with upregulation of the methanol utilisation pathway. This serves as a confirmation and validation of the array data obtained. Consistent with this, also various PEX genes were upregulated. The strong upregulation of ATG genes is possibly due to induction of autophagy processes related to remodeling of the cell architecture required to support growth on methanol. These processes may also be responsible for the enhanced peroxisomal β-oxidation, as autophagy leads to recycling of membrane lipids. The prominent downregulation of transcription and translation may be explained by the reduced growth rate on methanol (td glucose 1 h vs td methanol 4.5 h).
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                Author and article information

                Contributors
                gongyuchong@whu.edu.cn
                niuyanqing@mail.scuec.edu.cn
                zhangwen@mail.hzau.edu.cn
                leexh@whu.edu.cn
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                12 September 2019
                12 September 2019
                2019
                : 20
                : 468
                Affiliations
                [1 ]ISNI 0000 0001 2331 6153, GRID grid.49470.3e, School of Computer Science, , Wuhan University, ; Wuhan, 430072 China
                [2 ]ISNI 0000 0000 9147 9053, GRID grid.412692.a, School of Mathematics and Statistics, , South-Central University for Nationalities, ; Wuhan, 430074 China
                [3 ]ISNI 0000 0004 1790 4137, GRID grid.35155.37, College of Informatics, , Huazhong Agricultural University, ; Wuhan, 430070 China
                Article
                3063
                10.1186/s12859-019-3063-3
                6740005
                31510919
                b4af35cf-f86f-4ef5-a029-2d7e3818261a
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 May 2019
                : 29 August 2019
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: 61772381, 61572368
                Award Recipient :
                Funded by: the Fundamental Research Funds for the Central Universities
                Award ID: 2042017kf0219, 2042018kf0249
                Award Recipient :
                Funded by: National Key Research and Development Program
                Award ID: 2018YFC0407904
                Award Recipient :
                Funded by: Huazhong Agricultural University Scientific & Technological Self-innovation Foundation
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Bioinformatics & Computational biology
                mirna-disease associations,network embedding,random forest

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