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. 2018 Nov 6;126(11):117002. doi: 10.1289/EHP3281

Table 2.

Significantly enriched MetaCore process networks from 48-hpf Con-MO zebrafish developmentally exposed to 1 ng/mL TCDD for 1 h at the shield stage, compared to the vehicle control (0.1% DMSO).

Network name FDR Associated human gene
Development: Cartilage development 8.053×10−3 BMP4, BMP6, COL12A1, SOX9, CTGF
Cell adhesion: Cell-matrix interactions 8.053×10−3 COL12A1, THBS1, MMP9, VCAN, ITGA11, TNC, COL10A1
Immune response: Th17-derived cytokines 8.053×10−3 CXCL12, IL17RC, MMP9, JUN
Development: Ossification and bone remodeling 8.053×10−3 BMP4, BMP6, OSTN, FOXO1, COL10A1, POSTN
Signal Transduction: BMP and GDF signaling 8.053×10−3 BMP4, BMP6, CDKN1B, GADD45B, SOX9
Development: EMT: Regulation of epithelial-to-mesenchymal transition 8.053×10−3 BMP4, HMGA2, MMP9, JUN, CDKN1B, SOX9, CTGF
Proteolysis: ECM remodeling 8.053×10−3 MMP9, TNC, COL10A1, CTGF
Signal Transduction: ESR1-nuclear pathway 9.733×10−3 CYP1A1, CXCL12, BMP6, ADM, JUN, FOXO1, CYP1B1
Reproduction: FSH-beta signaling pathway 2.218×10−2 BMP4, JUN, FOXO1, CDKN1B, CTGF
Development: Blood vessel morphogenesis 2.424×10−2 EPAS1, CXCL12, BMP4, FOXO1, CTGF, ANGPT4

Note: The Bioconductor package edgeR (statistical methodology based on the negative binomial distribution) was used to calculate the significant differentially expressed genes (n=4, BH-adjusted p≤0.05), in comparison with the vehicle control (0.1% DMSO). The human orthologs of the gene list were then submitted to MetaCore to identify significantly enriched process networks using a hypergeometric distribution, where the p-value is the probability that a gene set maps to a manually curated GeneGo Process Network or is overrepresented in comparison with the background gene list. Enriched process networks were considered significant with an FDR≤ 0.05. BH, Benjamini-Hochberg; BMP, bone morphogenic protein; Con-MO, control morphant; DMSO, dimethyl sulfoxide; ECM, extracellular matrix; EMT, epithelial to mesenchyme transition; FDR, false discovery rate adjusted p-value; FSH-beta, follicle-stimulating hormone beta subunit; GDF, growth differentiation factor; hpf, hours post fertilization; slincR-MO, slincR morphant; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.