Fig. 2: Chemical-genetic profiling discriminates membrane-targeting and intracellular-targeting AMPs.
a Heatmap showing the ensemble clustering of the AMPs based on their chemical-genetic profiles (see Methods). For each AMP pair, the color code represents the frequency of being closest neighbors across the ensemble of clusters (n = 75,000 clustering). The four major clusters are labeled as C1, C2, C3, and C4. Membrane-targeting and intracellular-targeting broad modes of action are labeled with pink and orange, respectively, on the rightmost side of the figure. Gray color indicates that the specific broad mode of action has not been described or not tested (see Table 1). References describing these activities are provided in Supplementary Data 7. b Most important physicochemical properties that differentiated AMPs in cluster C1, C2 from AMPs in cluster C3, C4. Significant differences: **P = 0.0026 and 0.0012 for isoelectric point and relative number of prolines, respectively, * P = 0.0391 and P = 0.0154 for hydropathicity and total aggregation hotspot area, respectively, two-sided Mann–Whitney U test, n = 9 and n = 6 for C1, C2 and C3, C4, respectively. c, Physicochemical properties that distinguished the clusters when the 4 main AMP clusters were considered separately (p < 0.05 ANOVA, Tukey post-hoc test, n = 15). Significant differences: ***P = 1.1 × 10–6, P = 1.3 × 10−6 and P = 4 × 10−6 for C1 vs C4, C2 vs C4 and C3 vs C4, respectively in the case of number of disordered amino acids. *P = 0.034 and P = 0.027 for C1 vs C3 and C2 vs C3, respectively. **P = 0.0022 for C3 vs C4. ***P = 5.5 × 10−5 and P = 4.2 × 10−5 for C1 vs C4 and C2 vs C4, respectively, in the case of relative number of prolines. Central horizontal lines represent median values. Source data are provided as Supplementary Data 3.
