Modular Transcriptional Repertoire and microRNA target Analyses Characterize Genomic Dysregulation in the Thymus of Down Syndrome Infants

Trisomy 21- driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and microRNA-target analyses. 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 that allows the identification of modular transcriptional repertoires and the interactions between all the system’s constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS 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. The role of microRNAs in modulating the expression of highly connected genes in CT and DS was revealed through microRNA-target analysis. Trisomy 21 gene dysregulation in thymus may well be depicted as the breakdown and altered reorganization of transcriptional modules. Thymus miRNA transcriptomic profiles of patients with and without Down Syndrome were compared in order to identify differentially expressed transcripts.