Table 4.

Significantly enriched unique MetaCore GO processes related to skeletal and cartilage development from $48\text{-hpf}$ Con-MO zebrafish exposed to $1\text{ng}/\mathrm{mL}$ TCDD for 1 h at the shield stage, in comparison with the vehicle control (0.1% DMSO).

Biological process	FDR	Associated human gene
Ossification	$7.152\times {10}^{-5}$	CYP24A1, BMP4, BMP6, MMP9, OSTN, VCAN, ITGA11, TNC, SOX9, COL10A1, CTGF
Cartilage development	$2.601\times {10}^{-4}$	BMP4, BMP6, HMGA2, THBS1, SFRP2, SOX9, COL10A1, CTGF
Endochondral bone morphogenesis	$1.968\times {10}^{-3}$	BMP4, BMP6, THBS1, SOX9, COL10A1
Osteoblast differentiation	$4.093\times {10}^{-3}$	CYP24A1, BMP4, BMP6, VCAN, ITGA11, TNC
Bone development	$5.122\times {10}^{-3}$	BMP4, BMP6, THBS1, PAPPA2, SFRP2, SOX9, COL10A1
Regulation of chondrocyte differentiation	$5.710\times {10}^{-3}$	BMP4, BMP6, SOX9, CTGF
Chondrocyte differentiation	$1.142\times {10}^{-2}$	BMP4, HMGA2, SFRP2, SOX9
Regulation of cartilage development	$1.177\times {10}^{-2}$	BMP4, BMP6, SOX9, CTGF
Positive regulation of osteoblast differentiation	$1.271\times {10}^{-2}$	IL6R, BMP4, BMP6, SFRP2
Regulation of osteoblast differentiation	$1.324\times {10}^{-2}$	IL6R, BMP4, BMP6, OSTN, SFRP2
Regulation of bone mineralization	$1.356\times {10}^{-2}$	BMP4, BMP6, OSTN, SOX9
Odontogenesis of dentin-containing tooth	$1.356\times {10}^{-2}$	BMP4, ADM, FOXO1, TNC
Positive regulation of cartilage development	$1.567\times {10}^{-2}$	BMP4, BMP6, SOX9
Regulation of biomineral tissue development	$1.578\times {10}^{-2}$	BMP4, BMP6, OSTN, SOX9
Regulation of ossification	$1.793\times {10}^{-2}$	IL6R, BMP4, BMP6, OSTN, SFRP2, SOX9
Chondrocyte proliferation	$1.793\times {10}^{-2}$	HMGA2, CTGF
Endochondral ossification	$2.003\times {10}^{-2}$	BMP4, BMP6, COL10A1
Replacement ossification	$2.003\times {10}^{-2}$	BMP4, BMP6, COL10A1
Positive regulation of ossification	$2.891\times {10}^{-2}$	IL6R, BMP4, BMP6, SFRP2
Odontogenesis	$2.954\times {10}^{-2}$	BMP4, ADM, FOXO1, TNC
Negative regulation of chondrocyte differentiation	$4.076\times {10}^{-2}$	BMP4, SOX9

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 $p\le 0.05$), in comparison with the vehicle control (0.1% DMSO). The human orthologs of the gene list were then submitted to MetaCore to identify significant biological processes using a hypergeometric distribution, where the p-value is the probability that a gene set maps to a manually curated GO process or is overrepresented in comparison with the background gene list. Enriched GO processes were considered significant with an $\text{FDR}\le 0.05$. $\text{BH},\text{Benjamini-Hochberg}$; $\text{Con-MO},\text{control morphant}$; $\text{DMSO},\text{dimethyl sulfoxide}$; $\text{FDR},\text{false}\text{discovery}\text{rate}\text{adjusted}p\text{-value}$; $\text{GO},\text{gene}\text{ontology}$; $\text{hpf},\text{hours}\text{post}\text{fertilization}$; $\text{TCDD},2,3,7,8\text{-tetrachlorodibenzo-}p\text{-dioxin}$.