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从偏倚图定量评估配体偏倚:偏倚系数“kappa”。

Quantitative assessment of ligand bias from bias plots: The bias coefficient "kappa".

机构信息

Institute for NanoBioTechnology, Department of Materials Science and Engineering, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States of America.

Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States of America.

出版信息

Biochim Biophys Acta Gen Subj. 2023 Oct;1867(10):130428. doi: 10.1016/j.bbagen.2023.130428. Epub 2023 Jul 23.

Abstract

The current methods for quantifying ligand bias involve the construction of bias plots and the calculations of bias coefficients that can be compared using statistical methods. However, widely used bias coefficients can diverge in their abilities to identify ligand bias and can give false positives. As the empirical bias plots are considered the most reliable tools in bias identification, here we develop an analytical description of bias plot trajectories and introduce a bias coefficient, kappa, which is calculated from these trajectories. The new bias coefficient complements the tool-set in ligand bias identification in cell signaling research.

摘要

目前,量化配体偏向的方法涉及构建偏向图和计算可以使用统计方法进行比较的偏向系数。然而,广泛使用的偏向系数在识别配体偏向的能力上可能存在差异,并可能产生假阳性。由于经验偏向图被认为是识别偏向的最可靠工具,因此我们在这里对偏向图轨迹进行了分析描述,并引入了一个新的偏向系数 kappa,该系数是从这些轨迹中计算得出的。该新的偏向系数补充了细胞信号研究中配体偏向识别的工具集。

相似文献

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Quantitative assessment of ligand bias from bias plots: The bias coefficient "kappa".从偏倚图定量评估配体偏倚:偏倚系数“kappa”。
Biochim Biophys Acta Gen Subj. 2023 Oct;1867(10):130428. doi: 10.1016/j.bbagen.2023.130428. Epub 2023 Jul 23.
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Ligand bias in receptor tyrosine kinase signaling.配体偏倚在受体酪氨酸激酶信号转导中的作用。
J Biol Chem. 2020 Dec 25;295(52):18494-18507. doi: 10.1074/jbc.REV120.015190. Epub 2020 Oct 29.

本文引用的文献

1
Community guidelines for GPCR ligand bias: IUPHAR review 32.GPCR 配体偏向的社区准则:IUPHAR 评论 32。
Br J Pharmacol. 2022 Jul;179(14):3651-3674. doi: 10.1111/bph.15811. Epub 2022 Mar 27.
3
Ligand bias in receptor tyrosine kinase signaling.配体偏倚在受体酪氨酸激酶信号转导中的作用。
J Biol Chem. 2020 Dec 25;295(52):18494-18507. doi: 10.1074/jbc.REV120.015190. Epub 2020 Oct 29.
5
Receptor tyrosine kinase activation: From the ligand perspective.受体酪氨酸激酶激活:从配体角度看。
Curr Opin Cell Biol. 2020 Apr;63:174-185. doi: 10.1016/j.ceb.2020.01.016. Epub 2020 Feb 27.
6
Biased Receptor Signaling in Drug Discovery.药物发现中的偏向性受体信号转导
Pharmacol Rev. 2019 Apr;71(2):267-315. doi: 10.1124/pr.118.016790.
7
Strategies for the discovery of biased GPCR ligands.偏向性 G 蛋白偶联受体配体的发现策略。
Drug Discov Today. 2019 Apr;24(4):1031-1037. doi: 10.1016/j.drudis.2019.02.010. Epub 2019 Mar 1.
10
Analysis of Biased Agonism.偏向激动剂分析。
Prog Mol Biol Transl Sci. 2018;160:63-104. doi: 10.1016/bs.pmbts.2018.08.001. Epub 2018 Oct 15.

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