%0 Journal Article %T Prevalence and patterns of higher-order drug interactions in Escherichia coli %A Cynthia White %A Elif Tekin %A Mauricio Cruz-Loya %A Nina Singh %A Pamela J. Yeh %A Robert Damoiseaux %A Tina Manzhu Kang %A Van M. Savage %J Archive of "NPJ Systems Biology and Applications". %D 2018 %R 10.1038/s41540-018-0069-9 %X Experimental and theoretical setup for the characterization of higher-order interactions. Schematic representation of a drug combination plate, where the shaded well in the first row represents the control strain with no drug added and colored wells correspond to single or N-way (up to five-way) combinations from a set of drugs denoted by Xi. The N-way combinations of drugs are represented by wells divided into N identical slices with the colors signifying the drugs in the combination (see 1-drug row for each color). The concentration of each drug is kept the same across single, two-, three-, four-, and five-drug combination experiments. Here, the experimental setup is simplified for illustration, but in actuality, (1) we filled all wells with bacteria and drug combinations to obtain replicate measurements (see ˇ°Experimental detailsˇ±), and (2) we used multiple 96-well plates for each five-drug combination. From these experiments, fitness of bacteria (w) in the presence of drug combination (D) is assessed by the relative growth rate with respect to the no-drug control (WT). In the figure, schematics for the net N-way interaction include all possible lower-order connections, whereas an emergent interaction schematic connects all N drugs (such as dyad and triad for two- and three-drug combinations, respectively %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119685/