Drug-gene associations in coculture. (A) Boxplots showing response to nutlin 3a and ibrutinib stratified by culture condition and mutational status. (B) Comparison of drug-gene association statistics in monoculture and coculture. The x- and y-axes show the t statistic values of drug-gene associations in monoculture and coculture at a given concentration. (C) Effect size of IGHV and trisomy12 associations with BCR inhibitor response. The tick marks, colored by culture condition, show the absolute value of the effect size at 3 probed drug concentrations. Effect sizes of monoculture and coculture were compared using a 1-sided t test across all drugs shown. (D) The boxplots, colored by culture condition, show BCR inhibitor response stratified by IGHV mutational status [unmutated-CLL (U-CLL)/mutated-CLL(M-CLL)] and trisomy12 (negative/positive). The arrows indicate differences between monoculture and coculture medians, that is, viability gain in coculture. Monoculture and coculture were compared using a 1-sided t test. P values of all 4 groups were <1 × 10⁻¹⁰. (E) Drug response variability in CLL samples treated with BCR inhibitors, nutlin 3a, and proteasome inhibitors stratified by culture condition. The boxplots compare the interquartile ranges of drug sensitivities in monoculture and coculture.