ArticleiScience2021
Hidden suppressive interactions are common in higher-order drug combinations.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
The trial behind it
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Optimizing drug combinations to resurrect the potency of failed antibody therapy against emerging COVID-19 variants using IDentif.AI.Frontiers in digital health · 2026Article
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- Interactions within higher-order antibiotic combinations do not influence the rate of adaptation in bacteria.Evolution; international journal of organic evolution · 2025Article
- Resolving discrepancies between chimeric and multiplicative measures of higher-order epistasis.Nature communications · 2025Article
- The evolution of resistance to synergistic multi-drug combinations is more complex than evolving resistance to each individual drug component.Evolutionary applications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The rapid increase of multi-drug resistant bacteria has led to a greater emphasis on multi-drug combination treatments. However, some combinations can be suppressive-that is, bacteria grow faster in some drug combinations than when treated with a single drug. Typically, when studying interactions, the overall effect of the combination is only compared with the single-drug effects. However, doing so could miss "hidden" cases of suppression, which occur when the highest order is suppressive compared with a lower-order combination but not to a single drug. We examined an extensive dataset of 5-drug combinations and all lower-order-single, 2-, 3-, and 4-drug-combinations. We found that a majority of all combinations-54%-contain hidden suppression. Examining hidden interactions is critical to understanding the architecture of higher-order interactions and can substantially affect our understanding and predictions of the evolution of antibiotic resistance under multi-drug treatments.
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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.