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. 2021 Jun 25;12:3962. doi: 10.1038/s41467-021-23985-1

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© The Author(s) 2021

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a Heatmap showing differentially expressed phosphoproteins in ADH-1, ReACp53, and ADH-6 treated samples. Unsupervised hierarchical clustering reveals distinct segregation of ADH-1 vs ReACp53 and ADH-6. b Results from principal component analysis (PCA) showing that the main source of variation in the indicated groups was the compound/peptide treatment. c Venn diagram showing phosphoproteins that were differentially expressed in the ADH-6 vs ADH-1 and ReACp53 vs ADH-1 comparisons. The number of phosphoproteins that were unique or common in both comparisons are highlighted. d Gene set enrichment overlap analysis (GSEA) of hallmark signatures for the differentially expressed and downregulated phosphoproteins. Significance was assessed by q-value, or false discovery rate (FDR)-adjusted P-value, which was obtained from the hypergeometric P-value that was corrected for multiple hypothesis testing using the Benjamin and Hochberg procedure¹²². The hallmark signatures were ranked based on the −log10(q-value) of overlap. Only gene signatures that were significantly different (q-value <0.05 or −log10(q-value) >1.3) were further analyzed. e GOChord plot of phosphoproteins that belong to top dysregulated hallmark signatures (shown in d). The plot also depicts overlap of phosphoproteins between indicated gene signatures. Fold change of phosphoproteins (ADH-6 vs ADH-1) is represented by the blue track with the color spectrum depicting the level of reduction in phosphoprotein expression in the ADH-6 group. The biological roles of the downregulated phosphoproteins in ADH-6 were inferred from published data. The outer layer of the GOChord plot links the downregulation of phosphoproteins with the inhibition of DNA repair/replication and cell proliferation on the basis of previous reports (Supplementary Table 2a). f Protein–protein interaction (PPI) network map of upregulated phosphoproteins in ADH-6 vs ADH-1 treatments (biological roles of upregulated phosphoproteins are summarized in Supplementary Table 2b).