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      NinimHMDA: neural integration of neighborhood information on a multiplex heterogeneous network for multiple types of human Microbe–Disease association

      1 , 1
      Bioinformatics
      Oxford University Press (OUP)

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          Abstract

          Motivation

          Many computational methods have been recently proposed to identify differentially abundant microbes related to a single disease; however, few studies have focused on large-scale microbe-disease association prediction using existing experimentally verified associations. This area has critical meanings. For example, it can help to rank and select potential candidate microbes for different diseases at-scale for downstream lab validation experiments and it utilizes existing evidence instead of the microbiome abundance data which usually costs money and time to generate.

          Results

          We construct a multiplex heterogeneous network (MHEN) using human microbe-disease association database, Disbiome and other prior biological databases, and define the large-scale human microbe-disease association prediction as link prediction problems on MHEN. We develop an end-to-end graph convolutional neural network-based mining model NinimHMDA which can not only integrate different prior biological knowledge but also predict different types of microbe-disease associations (e.g. a microbe may be reduced or elevated under the impact of a disease) using one-time model training. To the best of our knowledge, this is the first method that targets on predicting different association types between microbes and diseases. Results from large-scale cross validation and case studies show that our model is highly competitive compared to other commonly used approaches.

          Availabilityand implementation

          The codes are available at Github https://github.com/yuanjing-ma/NinimHMDA.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

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          Most cited references19

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          Adam: A Method for Stochastic Optimization

          We introduce Adam, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. The method is straightforward to implement, is computationally efficient, has little memory requirements, is invariant to diagonal rescaling of the gradients, and is well suited for problems that are large in terms of data and/or parameters. The method is also appropriate for non-stationary objectives and problems with very noisy and/or sparse gradients. The hyper-parameters have intuitive interpretations and typically require little tuning. Some connections to related algorithms, on which Adam was inspired, are discussed. We also analyze the theoretical convergence properties of the algorithm and provide a regret bound on the convergence rate that is comparable to the best known results under the online convex optimization framework. Empirical results demonstrate that Adam works well in practice and compares favorably to other stochastic optimization methods. Finally, we discuss AdaMax, a variant of Adam based on the infinity norm. Published as a conference paper at the 3rd International Conference for Learning Representations, San Diego, 2015
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            Human symptoms-disease network.

            In the post-genomic era, the elucidation of the relationship between the molecular origins of diseases and their resulting phenotypes is a crucial task for medical research. Here, we use a large-scale biomedical literature database to construct a symptom-based human disease network and investigate the connection between clinical manifestations of diseases and their underlying molecular interactions. We find that the symptom-based similarity of two diseases correlates strongly with the number of shared genetic associations and the extent to which their associated proteins interact. Moreover, the diversity of the clinical manifestations of a disease can be related to the connectivity patterns of the underlying protein interaction network. The comprehensive, high-quality map of disease-symptom relations can further be used as a resource helping to address important questions in the field of systems medicine, for example, the identification of unexpected associations between diseases, disease etiology research or drug design.
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              Is Open Access

              A network integration approach for drug-target interaction prediction and computational drug repositioning from heterogeneous information

              The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug–target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for drug–target interaction prediction. Moreover, we experimentally validate the novel interactions between three drugs and the cyclooxygenase proteins predicted by DTINet, and demonstrate the new potential applications of these identified cyclooxygenase inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug–target interactions and repurpose existing drugs.
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                Author and article information

                Contributors
                Journal
                Bioinformatics
                Oxford University Press (OUP)
                1367-4803
                1460-2059
                December 15 2020
                April 05 2021
                January 08 2021
                December 15 2020
                April 05 2021
                January 08 2021
                : 36
                : 24
                : 5665-5671
                Affiliations
                [1 ]Department of Statistics, Northwestern University, Evanston, IL 60208, USA
                Article
                10.1093/bioinformatics/btaa1080
                33416850
                24d92dc7-d0c9-4a1a-9598-0ed56d552a88
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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