Integrated bioinformatics analysis of potential pathway biomarkers using abnormal proteins in clubfoot

PeerJ

article

Guiquan Cai¹  Xuan Yang²  Ting Chen²  Fangchun Jin²  Jing Ding²  Zhenkai Wu² 

[1] Department of Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University;Department of Pediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University

关键词: Congenital talipes equinovarus;    Clubfoot;    Etiological mechanisms;    Bioinformatics analysis;    Enrichment analysis;   

DOI  :  10.7717/peerj.8422

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundAs one of the most common major congenital distal skeletal abnormalities, congenital talipes equinovarus (clubfoot) affects approximately one in one thousandth newborns. Although several etiologies of clubfoot have been proposed and several genes have been identified as susceptible genes, previous studies did not further explore signaling pathways and potential upstream and downstream regulatory networks. Therefore, the aim of the present investigation is to explore abnormal pathways and their interactions in clubfoot using integrated bioinformatics analyses.MethodsKEGG, gene ontology (GO), Reactome (REAC), WikiPathways (WP) or human phenotype ontology (HP) enrichment analysis were performed using WebGestalt, g:Profiler and NetworkAnalyst.ResultsA large number of signaling pathways were enriched e.g. signal transduction, disease, metabolism, gene expression (transcription), immune system, developmental biology, cell cycle, and ECM. Protein-protein interactions (PPIs) and gene regulatory networks (GRNs) analysis results indicated that extensive and complex interactions occur in these proteins, enrichment pathways, and TF-miRNA coregulatory networks. Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins.ConclusionThe results of the present study supported previously proposed hypotheses, such as ECM, genetic, muscle, neurological, skeletal, and vascular abnormalities. More importantly, the enrichment results also indicated cellular or immune responses to external stimuli, and abnormal molecular transport or metabolism may be new potential etiological mechanisms of clubfoot.

【 授权许可】

CC BY