Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways

Abstract

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

“…However, few studies have explored the role of mitochondria in AS. There are only analytical studies that have predicted that the pathway of mitochondrial dysfunction and some mitochondrion-related proteins may be involved with AS 46,47 . In this study, we explored mitochondrial function in AS and discovered that the AS serum environment induced mitochondrial dysfunction in MSCs and subsequently raised ROS levels and caused MSCs senescence.…”

Bilobalide alleviates IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of microRNA‐125a

“…The JNK and NF‐κB signaling pathways played vital roles in the regulation of inflammation . Previous studies had reported that JNK and NF‐κB pathways are activated in AS, and the two pathways are involved in the pathogenesis of AS . Li et al found that IL‐17 inhibited new bone formation through JNK and NF‐κB pathways.…”