title: A sub-pathway based method to identify candidate agents for Ankylosing Spondylitis.
abstract: The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values < 0.1. Our study showed that neurotrophic signaling pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS.
authors.affiliation: Department of Orthopedics, Changhai Hospital, Shanghai 200433, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Yingchuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Wang
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Yushu
authors.initials: Y
authors.lastname: Bai
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use*; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000235:genetics
chemical_list: D054852:Small Molecule Libraries