Fig. 5: Differential proteoform co-aggregation analysis.
From: Deep thermal profiling for detection of functional proteoform groups
a, Schematic of the performed analysis. To obtain robust results, the F-statistic is computed based on the difference of the second highest (RSS(n−1)) and second lowest (RSS(2)) residual sum of squares between the two proteoforms in all cell lines. b, Volcano plot of the results of the analysis. RSS(n−1) − RSS(2) represents the effect size—that is, the difference between the profiles of proteoform A and B in the cell line with the second highest and second lowest distance. c, Profiles of CXXC1_2 and SETD1A_3 across cell lines showing their co-aggregation in some cell lines (gray background) and differential melting (white background) in other cell lines. d, Enrichment plot for genes part of the ‘p53-Independent DNA Damage Response’ set based on differentially expressed transcripts between cell lines with co-aggregation of CXXC1_2 and SETD1A_3 versus all others (NES = 1.82; Padj. = 0.01, Kolmogorov–Smirnov test with Benjamini–Hochberg method for multiple testing adjustment). e, Box plots of drug sensitivity of cell lines with CXXC1_2 and SETD1A_3 co-aggregation (n = 11) versus all others (n = 8) to two different nucleoside analogs. The P values shown were obtained from a two-sided Welch two-sample t-test. Center lines in all box plots represent the median; the bounds of the boxes are the 75th and 25th percentiles—that is, the interquartile range; and the whiskers correspond to the highest or lowest respective value.
