functionally annotated against known ontological categories, and additional features such as predicted drug interactions, using standard biological enrichment tools 25, 26. Representative gene ontology plots were visualized using semantic dimension scatter plots to reduce redundancy in terms of the identified biological groups. The coordinates of x- and y-axes are assigned using multidimensional scaling of similarities in ontological terms among identified groups. Overall results for functional enrichment of gene modules related to lifetime consumption can be found in supplementary materials (Table S2). Cell-type overrepresentation analysis was restricted to genes having ≥ 10-fold enrichment in neurons, astrocytes, or oligodendrocytes 27, permitting a rigorous assessment of gene clusters within the three main CNS cell-types. Unless indicated otherwise, statistical significance of intersecting gene-sets was evaluated using the Fisher’s exact test. Visualizations were rendered using cytoscape for biomolecular connections 28 and available R packages.
