ArticleCurrent genomics2018
Transcription Factor Co-expression Networks of Adipose RNA-Seq Data Reveal Regulatory Mechanisms of Obesity.
Article in Current genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 16 citations in OpenAlex.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranscription 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.
objectiveTo 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.
methodsWe 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.
resultsSingle 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).
conclusionOur results provide insights into the regulatory network of TFs and biologically relevant hub TFs in obesity.
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