PTM Analysis of DNA Repair Deficiencies
A. Mutational signatures associated with each cohort. Circle size represents the proportion of tumors. Circle color indicates median mutations/Mb.
B. Volcano plot illustrating the differential phosphorylation between HRD and HRP tumors. MMEJ genes are labeled.
C. Violin plot of 1st principal component projections based on the multi-omic signature activities for HRD tumors. Points are colored by their cancer type and separated by HRD cluster.
D.Schematic diagram of the acute and chronic hypoxia HRD clusters (top). Arrow length represents duration of hypoxia. Bubble plot showing GSEA results between the acute and chronic hypoxia HRD subgroups (bottom).
E. CausalPath results of differentially expressed DDR genes between acute and chronic hypoxia HRD tumors. Acute hypoxia upregulation (red), downregulation (blue). Black dashed lines - 90th percentile scoring substrates based on The Kinase Library results.
F. Bubble plot showing GSEA results between MMRD and MMRP tumors. MMRD pathways upregulated (red), downregulated (blue).
G. Violin plots showing protein abundance (top) and RNA (bottom) levels of MRN complex proteins between MMRD and MMRP tumors (COAD [circle] and UCEC [triangle]). RAD50 microsatellite frameshift indel samples indicated in red.
H. CausalPath results of differentially expressed DDR genes between MMRD and MMRP tumors as in panel E.