A multi-omic analysis of the dorsal striatum in an animal model of divergent genetic risk for alcohol use disorder.

Experimental Overview.

Differentially Expressed Gene Interaction Network.The 485 differentially expressed genes (log2 FC>±0.5, FDR<0.05) were submitted to String-db. Only high confidence interactions >0.9 with at least 1 connected gene are displayed. Node halo correlates with the log2 FC for HAP relative to LAP mice (red = increased expression and blue = decreased expression). Hub genes are highlighted in orange text. (n = 11 HAP and 12 LAP)

Differentially Expressed Protein Interaction Network.The 390 differentially expressed proteins (p<0.05) were submitted to String-db. Only high confidence interactions >0.9 with at least 1 connected node are displayed. Node halo corresponds to the log2 AR HAP relative to LAP mice (red = increased expression and blue = decreased expression). Node color represents identified proteins associated with the significantly enriched metabolic pathways KEGG Pathway (yellow) and the Synapse Cellular Component (green). Hub proteins are highlighted in orange text (n = 8 per line)

Differentially Expressed Phosphorylated Protein Interaction Network.The 345 unique proteins with differential peptide phosphorylations (p<0.05) were submitted to String-db. Only high confidence interactions >0.9 with at least 1 connected node are displayed. Node color represents identified proteins associated with the significantly enriched Synapse Cellular Component (green). Node halos are not present in this network because many proteins displayed more than one significant differentially expressed phosphopeptide between lines (n = 8 per line)

Integrated Analysis.A) Venn diagram demonstrating the number of mRNA transcripts (red), proteins (green), and phosphorylated proteins (blue) differentially expressed between lines and the overlap between each dataset. B) The correlation between mRNA and protein log2 FC and AR, respectively for the overlapping 87 mRNA transcripts and proteins differentially expressed between lines. Venn diagrams representing the overlapping, enriched GO terms discovered across all three omics analyses including C) biological processes, D) molecular function, and E) cellular component. Enriched F) Reactome and G) KEGG pathways discovered from both the proteomics and phosphoproteomic analysis. See supplementary table 1 for the associated overlapping genes, proteins, and phosphorylated proteins, and supplementary table 2 for the overlapping GO terms and pathways enriched