Thymus Gene Coexpression Networks: A Comparative Study in Children with and Without Down Syndrome

In this chapter we characterized trisomy 21-driven transcriptional alterations in human thymus through gene coexpression network (GCN) analysis. We used whole thymic tissue (corticomedullar sections)—obtained at heart surgery from Down syndrome (DS) and karyotipically normal individuals (CT)—and a network-based approach for GCN analysis allowing the study of interactions between all the system’s constituents based on community detection. Changes in the degree of connections observed for hierarchically important hubs in DS and CT gene networks corresponded to sub-network changes, i.e. module (communities) changes. Distinct communities of highly interconnected gene sets were topologically identified for DS and CT networks. Trisomy 21 gene dysregulation in thymus may therefore be viewed as the breakdown and altered reorganization of functional modules.