title: A subpathway-based method of drug reposition for polycystic ovary syndrome.
abstract: The need for development of new therapeutic agents for polycystic ovary syndrome (PCOS) is urgent due to general lack of efficient and specialized drugs currently available. We aimed to explore the metabolic mechanism of PCOS and inferred drug reposition for PCOS by a subpathway-based method. Using the GSE34526 microarray data from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between PCOS and normal samples. Then, we identified 13 significantly enriched metabolic subpathways that may be involved in the development of PCOS. Finally, by an integrated analysis of PCOS-involved subpathways and drug-affected subpathways, we identified 54 novel small molecular drugs capable to target the PCOS-involved subpathways. We also mapped the DEGs of PCOS and a potential novel drug (alprostadil) into purine metabolism pathway to illustrate the potentially active mechanism of alprostadil on PCOS. Candidate agents identified by our approach may provide insights into a novel therapy approach for PCOS.
authors.affiliation: Department of Reproductive Medicine Center, Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China liuhaiying0606@163.com.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Reproductive Medicine Center, Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Jian-Qiao
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Reproductive Medicine Center, Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Zi-Xin
authors.initials: ZX
authors.lastname: Mai
authors.affiliation: Department of Reproductive Medicine Center, Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Zeng
mesh_terms: D000527:Alprostadil / Q000627:therapeutic use*; D016022:Case-Control Studies; D019295:Computational Biology; D030541:Databases, Genetic; D058492:Drug Repositioning; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011687:Purines / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005819:Genetic Markers; D011687:Purines; D000527:Alprostadil
keywords: drug reposition; polycystic ovary syndrome; subpathway