Feb 6, 2016

Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants

Oncotarget
Carlos Alberto Moreira-FilhoMagda Carneiro-Sampaio

Abstract

Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue--obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT)--and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) 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 networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the "canonical" way of thymus functioning. Conversely, DS networks represent a "non-canonical" way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregul...Continue Reading

  • References238
  • Citations4

Mentioned in this Paper

Genome
Genes
Neoplasm of Uncertain or Unknown Behavior of Thymus
Transcription, Genetic
Discipline of Heart Surgery
RNA, Small Temporal
Kinetic Polymerase Chain Reaction
Disease of Thymus Gland
Down Syndrome
Reverse Transcriptase Polymerase Chain Reaction

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