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. 2022 Feb 2;12:1820. doi: 10.1038/s41598-022-05937-x

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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IPA enrichment analyses of ketamine-induced changes in protein phosphorylation in the dHPC of male and female rats. (A,B) Canonical pathway enrichment for phosphoproteins significantly differentially abundant in ketamine vs. saline-treated male (A) and female (B) rats 30 min following treatment. Based upon the direction of fold change of significant differentially abundant phosphoproteins within the dataset, the Z-Score serves as a predictor of pathway activation states by assessing the match between the observed and predicted (evidence-based) up/down regulation patterns⁴¹. Pathways are colored by predicted activation state: orange (activated) or blue (inhibited), where darker colors represent higher absolute Z-scores. Z-scores for pathways colored in gray could not be calculated due to insufficient evidence for a prediction of either activation or inhibition to be made. The ratio (solid orange line) represents the number of molecules within the comparison dataset meeting the cutoff criterion (p < 0.05; Fisher’s Exact Test), divided by the number of molecules comprising a given pathway within the reference set (Ingenuity Knowledge Base). Bar graphs were produced in Ingenuity Pathway Analysis (IPA) software (QIAGEN, Inc.).