title: Pathway analysis based on Monte Carlo Cross-Validation in polyarticular juvenile idiopathic arthritis.
abstract: BACKGROUND
  Juvenile idiopathic arthritis (JIA) is a common chronic disease with onset before the 16 years old in a child. Polyarticular JIA has been reported as the main form of JIA in several locations. Until now, understanding of the genetic basis of JIA is incomplete. The purpose of this study was to identify pathway pairs of great potential functional relevance in the progression of polyarticular JIA.
  
  
  METHODS
  Microarray data of 59 peripheral blood samples from healthy children and 61 samples from polyarticular JIA were transformed to gene expression data. Differential expressed genes (DEG) between patients and normal controls were identified using Linear Models for Microarray Analysis. After performed enrichment of DEG, differential pathways were identified with Fisher's test and false discovery rate. Differential pathway pairs were constructed with random two differential pathways, and were evaluated by Random Forest classification. Monte Carlo Cross-Validation was introduced to screen the best pathway pair.
  
  
  RESULTS
  42 DEG with P-values<0.01 were identified. 19 differential pathways with P-values<0.01 were identified. Area under the curve (AUC) of pathway pairs was generated with RF classification. After 50 bootstraps of Monte Carlo Cross-Validation, the best pathway pair with the highest AUC value was identified, and it was the pair of tumoricidal function of hepatic natural killer cells pathway and erythropoietin signaling pathway.
  
  
  CONCLUSIONS
  These identified pathway pairs may play pivotal roles in the progress of polyarticular JIA and can be applied for diagnosis. Particular attention can be focused on them for further research.
authors.affiliation: Department of Orthopaedics, The People's Hopital of Rizhao, Rizhao 276800, Shandong, PR China.
authors.forename: Shunhua
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics, The People's Hopital of Rizhao, Rizhao 276800, Shandong, PR China.
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, The People's Hopital of Donggang District, Rizhao 276800, Shandong, PR China.
authors.forename: Shunmei
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Orthopaedics, The People's Hopital of Rizhao, Rizhao 276800, Shandong, PR China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The People's Hopital of Rizhao, Rizhao 276800, Shandong, PR China.
authors.forename: Fangchang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedics, The Affiliated Hopital of Qingdao University, Qingdao 266000, Shandong, PR China. Electronic address: sunkangmed@yeah.net.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics* / Q000473:pathology; D002648:Child; D030541:Databases, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans
keywords: Differential expressed gene; Monte Carlo Cross-Validation; Pathway pair; Polyarticular juvenile idiopathic arthritis; Random forest classification