Transcription Factor Co-expression Networks of Adipose RNA-Seq Data Reveal Regulatory Mechanisms of Obesity

Current Genomics
Ruta Skinkyte-JuskieneHaja N Kadarmideen

Abstract

Transcription Factors (TFs) control actuation of genes in the genome and are key mediators of complex processes such as obesity. Master Regulators (MRs) are the genes at the top of a regulation hierarchy which regulate other genes. To elucidate clusters of highly co-expressed TFs (modules), involved pathways, highly inter-connected TFs (hub-TFs) and MRs leading to obesity and leanness, using porcine model for human obesity. We identified 817 expressed TFs in RNA-Sequencing dataset representing extreme degrees of obesity (DO; lean, obese). We built a single Weighted Transcription Factor Co-expression Network (WTFCN) and TF sub-networks (based on the DO). Hub-TFs and MRs (using iRegulon) were identi-fied in biologically relevant WTFCNs modules. Single WTFCN detected the Red module significantly associated with DO (P < 0.03). This module was enriched for regulation processes in the immune system, e.g.: Immune system process (Padj = 2.50E-06) and metabolic lifestyle disorders, e.g. Circadian rhythm - mammal pathway (Padj = 2.33E-11). Detected MR, hub-TF SPI1 was involved in obesity, immunity and osteoporosis. Within the obese sub-network, the Red module suggested possible associations with immunity, e.g. TGF-beta signaling pathway ...Continue Reading

Datasets Mentioned

BETA
GSE61271

Methods Mentioned

BETA
RNA-Seq

Software Mentioned

cutreeHybrid
WGCNA
STAR aligner
SScrofa10
iRegulon
NetworkAnalyzer
WTFCN
Cytoscape
GOseq R Bioconductor
Ensembl

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