Pathogenesis of axial spondyloarthropathy in a network perspective

Abstract

Complex chronic diseases are usually not caused by changes in a single causal gene but by an unbalanced regulating network resulting from the dysfunctions of multiple genes or their products. Therefore, network based systems approach can be helpful for the identification of candidate genes related to complex diseases and their relationships. The Axial spondyloarthropathy (SpA) is a group of chronic inflammatory joint diseases that mainly affects the spine and the sacroiliac joints, yet, the pathogenesis of SpA remains largely unknown. In this paper, we conducted a networked systems study on the pathogenesis of SpA. We integrated data related to SpA, from the OMIM database, proteomics and microarray experiments of SpA, to prioritize SpA candidate disease genes in the context of human protein interactome. Based on the top ranked SpA related genes, we constructed a PPI network and identified potential pathways associated with SpA. The PPI network and pathways reflect the well-known knowledge of SpA, i.e., immune mediated inflammation, as well as imbalanced bone modeling caused new bone formation and bone loss. This study may facilitate our understanding of the SpA pathogenesis from the perspective of network systems.