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CurveCurator:一种重新校准的 F 统计量,用于评估、分类和探索剂量反应曲线的显著性。

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

机构信息

Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, 85354, Freising, Germany.

German Cancer Consortium (DKTK), Partner Site Munich, 80336, Munich, Germany.

出版信息

Nat Commun. 2023 Nov 30;14(1):7902. doi: 10.1038/s41467-023-43696-z.

Abstract

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.

摘要

剂量反应曲线是药理学和生物学中的关键指标,用于定量评估生物活性化合物的表型或分子作用。然而,在高通量应用或不稳定的测定中,通常不清楚测量的反应是否与没有调节的曲线有显著差异,特别是在高通量应用或不稳定的测定中。以相同的置信水平对待随机和真实曲线的效价和效应大小估计,可能会导致错误的假设和机器学习模型训练中的问题。在这里,我们提出了 CurveCurator,这是一个开源软件,它通过基于重新校准的 F 统计量和考虑数据集特定效应大小分布的目标诱饵程序来计算 p 值和错误发现率,从而提供可靠的剂量反应特征。CurveCurator 在三个大型数据集上的应用实现了系统的药物作用模式分析,并通过一个高性能、交互式的仪表板来快速探索数据,展示了其在多个应用领域的可扩展性实用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af7e/10689459/32eb1fcd2c80/41467_2023_43696_Fig1_HTML.jpg

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