A Novel Method for Pathway Identification Based on Attractor and Crosstalk in Polyarticular Juvenile Idiopathic Arthritis

一种基于吸引子和串扰的多关节型幼年特发性关节炎通路识别新方法

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Abstract

BACKGROUND Juvenile idiopathic arthritis (JIA) is one of the most common inflammatory disorders of unknown etiology. We introduced a novel method to identify dysregulated pathways associated with polyarticular JIA (pJIA). MATERIAL AND METHODS Gene expression profiling of 61 children with pJIA and 59 healthy controls were collected from E-GEOD-13849; 300 pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) database and 787,896 protein-protein interaction sets were gathered from the Retrieval of Interacting Genes. Attractor and crosstalk were designed to complement each other to increase the integrity of pathways assessment. Then, impact factor was used to assess the interactions inter-pathways, and RP-value was used to evaluate the comprehensive influential ability of attractors. RESULTS There were seven attractors with p<0.01 and 14 pathways with RP<0.01. Finally, two significantly dysfunctional pathways were found, which were related to pJIA progression: p53 signaling pathway (KEGG ID: 04115) and non-alcoholic fatty liver disease (NAFLD) (KEGG ID: 04932). CONCLUSIONS A novel approach that identified the dysregulated pathways in pJIA was constructed based on attractor and crosstalk. The new process is expected to be efficient in the upcoming era of medicine.

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