ArticleJournal of the Royal Society, Interface2016
Uncovering emergent interactions in three-way combinations of stressors.
Article in Journal of the Royal Society, Interface, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Interactions within higher-order antibiotic combinations do not influence the rate of adaptation in bacteria.Evolution; international journal of organic evolution · 2025Article
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- High-throughput characterization of bacterial responses to complex mixtures of chemical pollutants.Nature microbiology · 2024Article
- The evolution of resistance to synergistic multi-drug combinations is more complex than evolving resistance to each individual drug component.Evolutionary applications · 2023Article
- Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications.bioRxiv : the preprint server for biology · 2023Article
- Global epistasis on fitness landscapes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design.PLoS computational biology · 2022Article
- Systematic measurement of combination-drug landscapes to predict in vivo treatment outcomes for tuberculosis.Cell systems · 2021Article
- Article
- Charting the Fragmented Landscape of Drug Synergy.Trends in pharmacological sciences · 2020Review
- Mining and visualizing high-order directional drug interaction effects using the FAERS database.BMC medical informatics and decision making · 2020Article
- Guided screen for synergistic three-drug combinations.PloS one · 2020Article
- COMBSecretomics: A pragmatic methodological framework for higher-order drug combination analysis using secretomics.PloS one · 2020Article
- Article
- COMBImage2: a parallel computational framework for higher-order drug combination analysis that includes automated plate design, matched filter based object counting and temporal data mining.BMC bioinformatics · 2019Article
- Noise-precision tradeoff in predicting combinations of mutations and drugs.PLoS computational biology · 2019Article
- Prediction of ultra-high-order antibiotic combinations based on pairwise interactions.PLoS computational biology · 2019Article
- Diagonal Method to Measure Synergy Among Any Number of Drugs.Journal of visualized experiments : JoVE · 2018Article
- Prevalence and patterns of higher-order drug interactions inNPJ systems biology and applications · 2018Article
- A general pharmacodynamic interaction model identifies perpetrators and victims in drug interactions.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two component) interactions have been lacking. Here, we conduct experiments using 20 three-drug combinations and their effects on the bacterial growth of Escherichia coli We report our measurements of growth rates in single, pairwise and triple-drug combinations. To uncover emergent interactions, we derive a simple framework to calculate expectations for three-way interactions based on the measured impact of each individual stressor and of each pairwise interaction. Using our framework, we find that (i) emergent antagonisms are more common than emergent synergies and (ii) emergent antagonisms are more common and emergent synergies are more rare than would be inferred from measures of net effects that do not disentangle pairwise interactions from three-way interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.