Extended Data Fig. 2: Chemical genetics metric captures well prior information and can be used to reclassify a subset of prior interactions.
From: Systematic mapping of antibiotic cross-resistance and collateral sensitivity with chemical genetics
a,b, Comparison of previously reported XR (a) and CS (b) interactions with our inferences based on our chemical genetics metric (OCDM) show an agreement of 67–68% for CS (n=17) and XR (n=47) - 10 such interactions were validated experimentally during our benchmarking (Fig. 3b,d). The rest is inferred as neutral or the opposite interaction by OCDM, including seven interactions (4 CS, 2 neutral & 1 XR) that we experimentally validated that OCDM inference was correct (Fig. 3b,d). c, In contrast to CS or XS, there is less agreement for neutral interactions with previous studies. This is consistent with the high false negative rates when comparing prior studies between them (Fig. 2a). The majority of previously reported neutral interactions (76.6%, n=85) are inferred as CS/XR by chemical genetics. 11/13 we included in the benchmarking set were confirmed as inferred by OCDM. The other two were inferred CS, but although most lineages exhibited CS, a single lineage exhibited XR, and hence called XR (Fig. 3b–d). d, New XR, neutral, and CS pairs inferred by chemical genetics and the OCDM cutoff are 2.8- and 6.4-fold more than currently known XR and CS antibiotic interactions in E. coli, after reclassifying interactions (n = 116) we infer differently than previously reported. The plot includes known interactions for which chemical genetics data is not available. e, Resistance against 12 antibiotics was evolved again for up to ~100 generations in 12 lineages. The MIC of evolved populations was measured at ~50 and ~100 generations for the same lineages in different antibiotics, allowing us to assess XR/CS for 17 drug pairs in both directions. Data are represented and drug pairs are numbered as in Fig. 3b,d. All inferred interactions were validated at both ~50 and ~100 generations. The length of experimental evolution affected the XR/CS of individual lineages and to a lower degree the cumulative call of the drug pair.
