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Construction and Analysis of Molecular Association Network by Combining Behavior Representation and Node Attributes

A key aim of post-genomic biomedical research is to systematically understand and model complex biomolecular activities based on a systematic perspective. Biomolecular interactions are widespread and interrelated, multiple biomolecules coordinate to sustain life activities, any disturbance of these...

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Detalles Bibliográficos
Autores principales: Yi, Hai-Cheng, You, Zhu-Hong, Guo, Zhen-Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854842/
https://www.ncbi.nlm.nih.gov/pubmed/31788002
http://dx.doi.org/10.3389/fgene.2019.01106
Descripción
Sumario:A key aim of post-genomic biomedical research is to systematically understand and model complex biomolecular activities based on a systematic perspective. Biomolecular interactions are widespread and interrelated, multiple biomolecules coordinate to sustain life activities, any disturbance of these complex connections can lead to abnormal of life activities or complex diseases. However, many existing researches usually only focus on individual intermolecular interactions. In this work, we revealed, constructed, and analyzed a large-scale molecular association network of multiple biomolecules in human by integrating associations among lncRNAs, miRNAs, proteins, drugs, and diseases, in which various associations are interconnected and any type of associations can be predicted. We propose Molecular Association Network (MAN)–High-Order Proximity preserved Embedding (HOPE), a novel network representation learning based method to fully exploit latent feature of biomolecules to accurately predict associations between molecules. More specifically, network representation learning algorithm HOPE was applied to learn behavior feature of nodes in the association network. Attribute features of nodes were also adopted. Then, a machine learning model CatBoost was trained to predict potential association between any nodes. The performance of our method was evaluated under five-fold cross validation. A case study to predict miRNA-disease associations was also conducted to verify the prediction capability. MAN-HOPE achieves high accuracy of 93.3% and area under the receiver operating characteristic curve of 0.9793. The experimental results demonstrate the novelty of our systematic understanding of the intermolecular associations, and enable systematic exploration of the landscape of molecular interactions that shape specialized cellular functions.