Abstract
The aim of the present study was to predict pathogenic genes for primary myelofibrosis (PMF) using a system‑network approach by combining protein‑protein interaction (PPI) network and gene expression data with known pathogenic genes. PMF gene expression profiles, known pathogenic genes and protein‑protein interactions were obtained. Using these data, differentially expressed genes (DEGs) were identified between PMF and normal conditions using significance analysis of microarrays, and seed genes were determined based on the intersection of known pathogenic genes and the PMF gene expression profile. A new network was constructed using the seed genes and their adjacent DEGs within the PPI network. Subsequently, a pathogenic network was extracted from the new network, and contained genes that interacted with at least two seed genes, and the candidate pathogenic genes were predicted based on the cohesion with seed genes. Cluster analysis was performed to mine the pathogenic modules from the pathogenic network, and functional analysis was performed to identify the putative biological processes of the candidate pathogenic genes. Results from the present study identified 845 DEGs between PMF and normal conditions, and 45 seed genes in PMF were screened. Subsequently, a pathogenic network comprising 103 nodes and 265 interactions was constructed, and 4 pathogenic modules (modules A‑D) were mined from the pathogenic network. There were nine candidate pathogenic genes contained within Module A and four potential pathogenic genes, including E1A‑binding protein p300, RAS‑like proto‑oncogene A, von Willebrand factor and RAF‑1 proto‑oncogene, serine/threonine kinase, were identified that may be involved in the same biological process with the seed genes. This study predicted 10 candidate pathogenic genes and several signaling pathways that may be related to the pathogenesis of PMF using a system‑network approach. These predictions may shed light on the PMF pathogenesis and may provide guidelines for future experimental verification.