Fig. 4: A multi-OMICs approach to dissect the downstream effects of increased H3K4me2 levels in TNBC. | Nature Communications

Fig. 4: A multi-OMICs approach to dissect the downstream effects of increased H3K4me2 levels in TNBC.

From: A histone-centric multi-omics study shows that increased H3K4 methylation sustains triple-negative breast cancer phenotypes

Fig. 4

a Multi-OMICs analysis was performed in a small set of LuA and TN fresh frozen samples. ChIP-seq data from 7 LuA and 8 TN samples were integrated with RNA-seq from matched samples or TCGA data (shown) and proteomics data from matched samples/CPTAC data. b Multidimensional scaling (MDS) based on H3K4me2 read density at promoters and distal regions of LuA and TN samples. The distance between points indicates the leading fold-change (logFC) of the corresponding samples. The leading logFC is defined as the root-mean-square of the top 500 largest log2 fold changes between each pair of samples. c Plots of the mean read density of TN (black) and LuA (light blue) in TN unique (n = 5083), common (n = 21253) and LuA unique (n = 2936) regions. Solid lines show the mean density. Shaded area depicts the 95% confidence interval of the mean. RPGC: Reads per Genomic Content. d Peak annotation of TN unique, common and LuA unique peaks, which was performed at base pair level. e Distribution of RNA quantification values for genes that harbor H3K4me2 peaks in promoters and enhancers only in TN, both in LuA and TN and only in LuA samples. Box plots show the median (center line), the 25th and 75th percentiles (box edges), and whiskers that extend to the most extreme values within 1.5× the interquartile range. Outlier values are not displayed. TPM: transcripts per million. P values by two-tailed Wilcoxon rank-sum test: TN only promoters: 0.00068; TN only enhancers: 1.9e−10; LuA only promoter: 0.002; LuA only enhancer: 3.53e−13; Common promoter: 1.6e-05; Common enhancer: 1.9e−05. f Volcano plot showing TCGA gene expression comparison of TN and LuA tumor samples. Differentially expressed genes harboring H3K4me2 peaks only in LuA or only in TN are colored in light blue and black, respectively. Dark gray colored points depict differentially expressed genes that do not harbor peaks unique to either subtype. The DESeq2 two-tailed Wald test was used to identify differentially expressed genes (FDR < 0.05, log2FoldChange > |1|). g Over-representation analysis of genes with TN-unique H3K4me2 peaks and overexpressed in the same subtype. A one-sided hypergeometric test, implemented in the R package clusterProfiler, was used for enrichment analysis. Dn: down. P.adjust: p-value adjusted for multiple comparisons using the Benjamini-Hochberg correction.

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