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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (Padj = 1.73E-02) and osteoporosis, e.g. Osteoclast differentiation (Padj = 1.94E-02). Within the lean sub-network, the Magenta module displayed associations with type 2 diabetes, obesity and os-teoporosis e.g. Notch signaling pathway (Padj = 2.40E-03), osteoporosis e.g. hub-TF VDR (a prime candidate gene for osteoporosis). CONCLUSION: Our results provide insights into the regulatory network of TFs and biologically relevant hub TFs in obesity.

Differential expression and co-expression gene networks reveal candidate biomarkers of boar taint in non-castrated pigs.

Boar taint (BT) is an offensive odour or taste observed in pork from a proportion of non-castrated male pigs. Surgical castration is effective in avoiding BT, but animal welfare issues have created an incentive for alternatives such as genomic selection. In order to find candidate biomarkers, gene expression profiles were analysed from tissues of non-castrated pigs grouped by their genetic merit of BT. Differential expression analysis revealed substantial changes with log-transformed fold changes of liver and testis from -3.39 to 2.96 and -7.51 to 3.53, respectively. Co-expression network analysis revealed one module with a correlation of -0.27 in liver and three modules with correlations of 0.31, -0.44 and -0.49 in testis. Differential expression and co-expression analysis revealed candidate biomarkers with varying biological functions: phase I (COQ3, COX6C, CYP2J2, CYP2B6, ACOX2) and phase II metabolism (GSTO1, GSR, FMO3) of skatole and androstenone in liver to steroidgenesis (HSD17B7, HSD17B8, CYP27A1), regulation of steroidgenesis (STARD10, CYB5R3) and GnRH signalling (MAPK3, MAP2K2, MAP3K2) in testis. Overrepresented pathways included "Ribosome", "Protein export" and "Oxidative phosphorylation" in liver and "Steroid hormone biosynthesis" and "Gap junction" in testis. Future work should evaluate the biomarkers in large populations to ensure their usefulness in genomic selection programs.