Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen

Figure 4

Chemogenomic enrichment analysis of 50 chemicals that increase expression of genes downregulated in the critical period signatures reveals inflammatory, response to pathogen, and immune cell chemotaxis pathways. We computed gene set enrichments for the CHEM up library (1742 chemical signatures) across 5191 Gene Ontology (GO) Biological Process (BP) gene sets and 96 LINCS ligand gene sets to yield 9,042,722 and 167,232 enrichment values, which were corrected for multiple testing using the Benjamini and Hochberg approach. For each biological process or ligand, we calculated the overrepresentation of that gene set (if it was significant after multiple test correction) among the 50 chemicals identified as impacting both juvenile and Lynx1-/- critical period signatures, in comparison to the remaining 1692 chemicals, using a hypergeometric test (hypergea R package implementation). A pathway was considered associated with a chemical if the enrichment , yielding (a) 33 GO BP gene sets and (b) 48 LINCS ligand gene sets.

(a)

(b)