title: Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Much effort has been devoted to developing effective therapeutic agents. Recently, targeting microRNAs (miRNAs) with small molecules has become a novel therapy for human diseases. In this study, we present a systematic computational approach to construct a bioactive Small molecule and miRNA association Network in AD (SmiRN-AD), which is based on the gene expression signatures of bioactive small molecule perturbation and AD-related miRNA regulation. We also performed topological and functional analysis of the SmiRN-AD from multiple perspectives. At the significance level of p ≤ 0.01, 496 small molecule-miRNA associations, including 25 AD-related miRNAs and 275 small molecules, were recognized and used to construct the SmiRN-AD. The drugs that were connected with the same miRNA tended to share common drug targets (p = 1.72 × 10(-4)) and belong to the same therapeutic category (p = 4.22 × 10(-8)). The miRNAs that were linked to the same small molecule regulated more common miRNA targets (p = 6.07 × 10(-3)). Further analysis of the positive connections (quinostatin and miR-148b, amantadine and miR-15a) and the negative connections (melatonin and miR-30e-5p) indicated that our large-scale predictions afforded specific biological insights into AD pathogenesis and therapy. This study proposes a holistic strategy for deciphering the associations between small molecules and miRNAs in AD, which may be helpful for developing a novel effective miRNA-associated therapeutic strategy for AD. A comprehensive database for the SmiRN-AD and the differential expression patterns of the miRNA targets in AD is freely available at http://bioinfo.hrbmu.edu.cn/SmiRN-AD/.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, , 194 Xuefu Road, Harbin 150081, People's Republic of China.
authors.forename: Fanlin
authors.initials: F
authors.lastname: Meng
authors.forename: Enyu
authors.initials: E
authors.lastname: Dai
authors.forename: Xuexin
authors.initials: X
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.forename: Xinyi
authors.initials: X
authors.lastname: Liu
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Wang
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000547:Amantadine; D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011804:Quinolines; D054852:Small Molecule Libraries / Q000378:metabolism*
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D035683:MicroRNAs; D011804:Quinolines; D054852:Small Molecule Libraries; C524901:quinostatin; D000547:Amantadine
keywords: Alzheimer's disease; bioinformatics; drug; microRNA; small molecule; therapeutics