Dataset Information

Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response.

ABSTRACT: Despite Bisphenol-A (BPA) being subject to extensive study, a thorough understanding of molecular mechanism remains elusive. Here we show that using weighted gene correlation network analysis (WGCNA), which takes advantage of a graph theoretical approach to understanding correlations amongst genes and grouping genes into modules that typically have co-ordinated biological functions and regulatory mechanisms, that despite some commonality in altered genes, there is minimal overlap between BPA and estrogen in terms of network topology. We confirmed previous findings that ZNF217 and TFAP2C are involved in the estrogen pathway, and are implicated in BPA as well, although for BPA they appear to be active in the absence of canonical estrogen-receptor driven gene expression. Furthermore, our study suggested that PADI4 and RACK7/ZMYNDB8 may be involved in the overlap in gene expression between estradiol and BPA. Lastly, we demonstrated that even at low doses there are unique transcription factors that appear to be driving the biology of BPA, such as SREBF1. Overall, our data is consistent with other reports that BPA leads to subtle gene changes rather than profound aberrations of a conserved estrogen signaling (or other) pathways.

SUBMITTER: Maertens A

PROVIDER: S-EPMC6240694 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response.

Maertens Alexandra A Tran Vy V Kleensang Andre A Hartung Thomas T

Frontiers in genetics 20181112

Despite Bisphenol-A (BPA) being subject to extensive study, a thorough understanding of molecular mechanism remains elusive. Here we show that using weighted gene correlation network analysis (WGCNA), which takes advantage of a graph theoretical approach to understanding correlations amongst genes and grouping genes into modules that typically have co-ordinated biological functions and regulatory mechanisms, that despite some commonality in altered genes, there is minimal overlap between BPA and ...[more]

PMID: 30483308

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Project description:BACKGROUND Many patients are not responsive or tolerant to medical therapies for carotid atherosclerosis. Thus, elucidating the molecular mechanism for the pathogenesis and progression of carotid atherosclerosis and identifying new potential molecular targets for medical therapies that can slow progression of carotid atherosclerosis and prevent ischemic events are quite important. MATERIAL AND METHODS We downloaded the expression profiling data of PBMC in Biobank of Karolinska Endarterectomy (BiKE, GSE21545) for GEO. The WGCNA and DEG screening were conducted. The co-expression pattern between patients with ischemic events (the events group) and patients without ischemic events (the no-events group) were compared. Then, we identified hub genes of each module. Finally, the DEG co-expression network was constructed and MCODE was used to identify crucial genes based on this co-expression network. RESULTS In the study, 183 DEGs were screened and 8 and 6 modules were assessed in the events group and no-events group, respectively. Compared to the no-events group, genes associated with inflammation and immune response were clustered in the green-yellow module of the events group. The hub gene of the green-yellow module of the events group was KIR2DL5A. We obtained 1 DEG co-expression network, which has 16 nodes and 24 edges, and we detected 5 crucial genes: SIRT1, THRAP3, RBM43, PEX1, and KLHDC2. The upregulated genes (THRAP3 and RBM43) showed potential diagnostic and prognostic value for the occurrence of ischemic events. CONCLUSIONS We detected 8 modules for the events group and 6 modules for the no-events group. The hub genes for modules and crucial genes of the DEG co-expression network were also identified. These genes might serve as potential targets for medical therapies and biomarkers for diagnosis and prognosis. Further experimental and biological studies are needed to elucidate the role of these crucial genes in the progression of carotid atherosclerosis.

Project description:Somatic embryogenesis (SE), which occurs naturally in many plant species, serves as a model to elucidate cellular and molecular mechanisms of embryo patterning in plants. Decoding the regulatory landscape of SE is essential for its further application. Hence, the present study was aimed at employing Weighted Gene Correlation Network Analysis (WGCNA) to construct a gene coexpression network (GCN) for Arabidopsis SE and then identifying highly correlated gene modules to uncover the hub genes associated with SE that may serve as potential molecular targets. A total of 17,059 genes were filtered from a microarray dataset comprising four stages of SE, i.e., stage I (zygotic embryos), stage II (proliferating tissues at 7 days of induction), stage III (proliferating tissues at 14 days of induction), and stage IV (mature somatic embryos). This included 1,711 transcription factors and 445 EMBRYO DEFECTIVE genes. GCN analysis identified a total of 26 gene modules with the module size ranging from 35 to 3,418 genes using a dynamic cut tree algorithm. The module-trait analysis revealed that four, four, seven, and four modules were associated with stages I, II, III, and IV, respectively. Further, we identified a total of 260 hub genes based on the degree of intramodular connectivity. Validation of the hub genes using publicly available expression datasets demonstrated that at least 78 hub genes are potentially associated with embryogenesis; of these, many genes remain functionally uncharacterized thus far. In silico promoter analysis of these genes revealed the presence of cis-acting regulatory elements, "soybean embryo factor 4 (SEF4) binding site," and "E-box" of the napA storage-protein gene of Brassica napus; this suggests that these genes may play important roles in plant embryo development. The present study successfully applied WGCNA to construct a GCN for SE in Arabidopsis and identified hub genes involved in the development of somatic embryos. These hub genes could be used as molecular targets to further elucidate the molecular mechanisms underlying SE in plants.

Project description:Our previous studies shown that syndecan-1 (SDC1) may be a novel class of biomarkers for the diagnosis and treatment of glioma, but its specific roles and the in-depth molecular mechanism remain elusive. Here, we used Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithms and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms to evaluate the immune score of tumor samples and quantify the relative infiltration of immune cells in the tumor microenvironment (TME), respectively, in different data sets obtained from the Chinese Glioma Genome Atlas and The Cancer Gene Atlas. Next, we calculate the correlation of the immune score and immune cells with SDC1, respectively. To identify the specific process regulated by SDC1, the differentially expressed genes (DEGs) analysis between the high and low expression of SDC1 of glioma samples were used to discover the hub genes through Weighted Gene Coexpression Network Analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed cardinal biological processes and pathways involved in genes and tumor grade correlation and survival analysis verified its significance in glioma. The results show that SDC1 is associated with the immune infiltration of glioma in the TME, especially activated CD4+T cells and CD8+T cells. The three data sets filter 8,887 DEGs, the genes in the blue modules were selected as hub genes in WGCNA. GO and KEGG analysis found eight genes in the blue modules involved in antigen processing and presentation in T cells in glioma. Kaplan-Meier estimator and log-rank test statistic determined that the introduced genes are associated with poor prognosis in glioma. Protein-protein network interaction analysis showed that SDC1 may regulate antigen processing and presentation through CTSL or CD4 in glioma. Finally, this study provided insights and clues for the next research direction of SDC1 and identified the key pathways and genes that might participate in the immune escape of glioma. These results might provide a new insight on the study of immune infiltration of glioma in the future.

Dataset Information

Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response.

Publications

Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response.

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