Transcription factor co-expression networks of adipose RNA-Seq data reveal regulatory mechanisms of obesity
Research output: Contribution to journal › Journal article › Research › peer-review
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 interconnected 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 identified 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 osteoporosis 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.
Original language | English |
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Journal | Current Genomics |
Volume | 19 |
Issue number | 4 |
Pages (from-to) | 289-299 |
Number of pages | 11 |
ISSN | 1389-2029 |
DOIs | |
Publication status | Published - 2018 |
- Gene networks, Obesity, RNA-Seq, Transcription factors, Transcriptomics, WGCNA
Research areas
Links
- http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5930450&blobtype=pdf
Accepted author manuscript
ID: 202028660