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. Author manuscript; available in PMC: 2024 Sep 1.
Published in final edited form as: Neurotoxicol Teratol. 2023 Jul 11;99:107286. doi: 10.1016/j.ntt.2023.107286

Table 1:

Significant biological process gene ontology terms identified through DAVID pathway analysis of significant (p<0.05) proteins that were increased or decreased for VYS and EMB.

Visceral Yolk Sac
Decreased Increased

2 hr Ribosome biogenesis Short-term memory

Negative regulation of ATPase activity
4 hr Positive regulation of protein ubiquitination involved in ubiquitin-dependent Cell migration
protein catabolic process

6 hr Cellular response to hydrogen peroxide
Regulation of cell proliferation
- Proteolysis
DNA methylation
Negative regulation of canonical Wnt signaling
pathway

8 hr Regulation of centrosome duplication -
Cellular response to interleukin-1
NLS-bearing protein import into nucleus

10 hr Negative regulation of gene expression
Transport Thymus development
Lipoprotein transport Thyroid gland development
Bone development Regulation of cell proliferation
Heart development Transcription, DNA-templated
Actin cytoskeleton organization Positive regulation of cell migration
Protein stabilization

Embryo

Wnt signaling pathway, planar cell polarity
2 hr - pathway
Neural tube closure
Convergent extension involved in
organogenesis

4 hr Regulation of transcription, DNA-templated Methylation
Cellular response to DNA damage stimulus Ribosomal small subunit assembly
Rac protein signal transduction S-adenosylmethioninamine metabolic process
Barbed-end actin filament capping Translation
Regulation of protein kinase C signaling Cell-matrix adhesion
Immune system process Cellular response to amino acid stimulus
Cellular response to transforming growth factor
beta stimulus

6 hr Bicellular tight junction assembly
- Myelin assembly
Attachment of GPI anchor to protein

8 hr Response to amino acid Ribosome biogenesis
DNA replication rRNA processing
Positive regulation of macroautophagy Single organismal cell-cell adhesion
DNA replication initiation Ribosomal small subunit assembly
Response to cadmium ion Ventricular cardiac muscle cell action potential
Post-translational protein acetylation rRNA methylation
Positive regulation of stress fiber assembly

10 hr Alpha-beta T cell differentiation Metabolic Process
Negative regulation of endothelial cell
apoptotic process
Cell motility

In addition to pathway analysis based on categorization of proteins into groups increased and decreased by VPA exposure, pre-ranked Gene Set Enrichment Analysis (GSEA) was also performed. In the EMB, GSEA identified 46 developmentally relevant pathways that were more enriched in proteins that increased in abundance following VPA exposure and seven pathways that were more enriched in decreased proteins (Supplemental Table 2). There was no enrichment of developmental pathways at 4 hr for increased proteins, or 6, 8, and 10 hr for decreased proteins.