Connectivity Map analysis

The Broad Institute Connectivity Map (CMap, https://clue.io/cmap) is a database with a collection of gene expression profiles that are obtained from cultured human cell lines treated with small pharmacological compounds15. We queried CMap (CMap_build02) with up and downregulated gene lists from wild-type versus importin α5 knockout hippocampi (GEO accession number {"type":"entrez-geo","attrs":{"text":"GSE106546","term_id":"106546"}}GSE106546). CMap then scored the similarity of the up and down lists with the deposited expression profiles. As a result, the similarity of the transcriptional responses is scored for each small molecule. An enrichment score of “1” indicates a perfect correlation, where genes in the up-list are upregulated and the genes in the down-list are downregulated in a CMap microarray data. Because our RNA-seq data were obtained from mouse samples, and CMap data are obtained from human cell lines with the Affymetrix HG-U133A microarray chip, we used a custom-made MATLAB script to convert the mouse gene identifiers to their human orthologs gene identifiers.