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Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.

ABSTRACT: Antibiotic resistance is an important public health problem. One potential solution is the development of synergistic antibiotic combinations, in which the combination is more effective than the component drugs. However, experimental progress in this direction is severely limited by the number of samples required to exhaustively test for synergy, which grows exponentially with the number of drugs combined. We introduce a new metric for antibiotic synergy, motivated by the popular Fractional Inhibitory Concentration Index and the Highest Single Agent model. We also propose a new experimental design that samples along all appropriately normalized diagonals in concentration space, and prove that this design identifies all synergies among a set of drugs while only sampling a small fraction of the possible combinations. We applied our method to screen two- through eight-way combinations of eight antibiotics at 10 concentrations each, which requires sampling only 2,560 unique combinations of antibiotic concentrations.

SUBMITTER: Brennan J

PROVIDER: S-EPMC9333450 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.

Brennan Jennifer J Jain Lalit L Garman Sofia S Donnelly Ann E AE Wright Erik Scott ES Jamieson Kevin K

PLoS computational biology 20220718 7

Antibiotic resistance is an important public health problem. One potential solution is the development of synergistic antibiotic combinations, in which the combination is more effective than the component drugs. However, experimental progress in this direction is severely limited by the number of samples required to exhaustively test for synergy, which grows exponentially with the number of drugs combined. We introduce a new metric for antibiotic synergy, motivated by the popular Fractional Inhi ...[more]

PMID: 35849634

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Dataset Information

Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.

Publications

Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.

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