Figure 3 from The Effect of Exposure to Neighborhood Violence on Glucocorticoid Receptor Signaling in Lung Tumors

Abstract

<p>Distinct pathways altered within the GR cistrome in response to violent crime. <b>A,</b> Binding site distribution of GR in tumor samples and healthy tissue samples by low, mid, and high exposure to violence. Bam files for individual samples were merged by exposure to violence grouping. Merged tumor and merged normal bed files were generated relative to merged input files. Binding site distribution from these merged bed files was generated using ChIPSeeker. <b>B,</b> Comparison of enriched GR binding sites in tumor compared to healthy tissue samples. For each sample, tumor and healthy tissue bed files were generated by filtering out binding sites observed in the input. For each patient, the top 10% of enriched binding sites for tumor and healthy tissue were plotted and compared using the Kolmogorov–Smirnov test. A cutoff of 10% was selected to ensure a high confidence level in GR binding sites, as the top 10% of binding sites exhibited a high magnitude of GR binding. <b>C,</b> Comparison of the magnitude of GR binding sites from high-violence tumor samples in tumor vs. normal samples in high-violence vs. low-violence samples. BAM files for individual samples were merged by exposure to violence grouping. A merged bed file of high-violence tumor sample binding sites was generated relative to input binding sites. Merged sBAM files were generated using merged BAM files and the merged bed file. Heatmaps visualizing the magnitude of GR recruitment to chromatin were generated using Deeptools, and clusters were generated using the kmeans clustering algorithm. Darker shading indicates an increased magnitude of GR binding. <b>D,</b> Motif analysis of binding sites in clusters 1 to 5 and cluster 6 from (<b>C</b>). Motif analysis was performed using Homer. <b>E,</b> Pathway analysis of annotated genes from clusters 6 and 7 visualized in (<b>C</b>). Genes were annotated using GREAT analysis, and pathway analysis was performed in DAVID using Biocarta, Kegg, and Wikipathways analysis. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.0001; ****, <i>P</i> < 0.000001. Abbreviations. T, tumor; N, normal; Low, low exposure to violence; Mid, mid exposure to violence; High, high exposure to violence.</p>