Revealing hub pathway cross-talk for premature newborns with bronchopulmonary dysplasia by the integration of pathway analysis and Monte Carlo Cross-Validation

The objective of this study was to reveal hub pathway cross-talk for premature newborns with bronchopulmonary dysplasia (BPD) based on the pathway enrichment analysis and Monte Carlo Cross-Validation (MCCV) method. The inference of key pathway cross-talk consisted of four parts: i) Identifying differentially expressed genes (DEGs); ii) detecting differentially expressed pathways (DEPs); iii) computing discriminating score (DS) for each pair of DEPs or cross-talk and investigating seed cross-talk through the random forest (RF) algorithm and iv) extracting hub cross-talk dependent on the MCCV method. The results showed that a total of 132 DEGs and 137 DEPs were obtained across BPD patients and normal controls. Using the DS and RF algorithm, 10 seed DEP cross-talk were detected. By conducting the MCCV on seed cross-talk, 3 hub cross-talk for BPD were uncovered: i) The pair of pathways role of interleukin-17F (IL-17F) in allergic inflammatory airway diseases and role of IL-17A in psoriasis; ii) the pair of pathways role of IL random forest 17A in psoriasis and IL-17A signaling in fibroblasts and ii) the pair of pathways IL-17A signaling in airway cells and role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza. These 3 hub cross-talk among DEPs might give an insight to reveal the molecular mechanism underlying the premature newborns with BPD.