Qiagen Ingenuity Pathway Analysis (IPA, QIAGEN, Redwood City, version Winter 2015) was used to identify pathways that are significantly enriched in differentially expressed (FDR ≤ 0.05) genes. Upstream regulator analysis uses the curated knowledge base to identify molecules that could possibly be responsible for the observed changes in gene expression. Upstream regulators can be proteins and other endogenous factors or exogenous factors such as drugs. A positive z-score suggests the regulator is active and a negative z-score suggests the regulator is inhibited; the magnitude indicates the strength of the predicted effect. In the case of exogenous factors, a positive z-score indicates the effect expected if the factor were added and a negative z-scores indicates that changes in expression of downstream targets are opposite what would be expected if the factor is added, thus addition of the factor might be able to reverse the effects. Putative target genes of upstream regulators are also identified. A white paper description of the z-score calculation is available at: http://pages.ingenuity.com/rs/ingenuity/images/0812%20upstream_regulator_analysis_whitepaper.pdf. IPA comparison analysis was used to compare pathway and upstream results from the four brain
