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CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves

Dose-response curves are key metrics in pharmacology and biology to assess phenotypic or molecular actions of bioactive compounds in a quantitative fashion. Yet, it is often unclear whether or not a measured response significantly differs from a curve without regulation, particularly in high-through...

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Autores principales: Bayer, Florian P., Gander, Manuel, Kuster, Bernhard, The, Matthew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689459/
https://www.ncbi.nlm.nih.gov/pubmed/38036588
http://dx.doi.org/10.1038/s41467-023-43696-z
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author Bayer, Florian P.
Gander, Manuel
Kuster, Bernhard
The, Matthew
author_facet Bayer, Florian P.
Gander, Manuel
Kuster, Bernhard
The, Matthew
author_sort Bayer, Florian P.
collection PubMed
description Dose-response curves are key metrics in pharmacology and biology to assess phenotypic or molecular actions of bioactive compounds in a quantitative fashion. Yet, it is often unclear whether or not a measured response significantly differs from a curve without regulation, particularly in high-throughput applications or unstable assays. Treating potency and effect size estimates from random and true curves with the same level of confidence can lead to incorrect hypotheses and issues in training machine learning models. Here, we present CurveCurator, an open-source software that provides reliable dose-response characteristics by computing p-values and false discovery rates based on a recalibrated F-statistic and a target-decoy procedure that considers dataset-specific effect size distributions. The application of CurveCurator to three large-scale datasets enables a systematic drug mode of action analysis and demonstrates its scalable utility across several application areas, facilitated by a performant, interactive dashboard for fast data exploration.
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spelling pubmed-106894592023-12-02 CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves Bayer, Florian P. Gander, Manuel Kuster, Bernhard The, Matthew Nat Commun Article Dose-response curves are key metrics in pharmacology and biology to assess phenotypic or molecular actions of bioactive compounds in a quantitative fashion. Yet, it is often unclear whether or not a measured response significantly differs from a curve without regulation, particularly in high-throughput applications or unstable assays. Treating potency and effect size estimates from random and true curves with the same level of confidence can lead to incorrect hypotheses and issues in training machine learning models. Here, we present CurveCurator, an open-source software that provides reliable dose-response characteristics by computing p-values and false discovery rates based on a recalibrated F-statistic and a target-decoy procedure that considers dataset-specific effect size distributions. The application of CurveCurator to three large-scale datasets enables a systematic drug mode of action analysis and demonstrates its scalable utility across several application areas, facilitated by a performant, interactive dashboard for fast data exploration. Nature Publishing Group UK 2023-11-30 /pmc/articles/PMC10689459/ /pubmed/38036588 http://dx.doi.org/10.1038/s41467-023-43696-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bayer, Florian P.
Gander, Manuel
Kuster, Bernhard
The, Matthew
CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title_full CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title_fullStr CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title_full_unstemmed CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title_short CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
title_sort curvecurator: a recalibrated f-statistic to assess, classify, and explore significance of dose–response curves
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689459/
https://www.ncbi.nlm.nih.gov/pubmed/38036588
http://dx.doi.org/10.1038/s41467-023-43696-z
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