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迈向使用广义类推法(GenRA)进行系统的类推。

Towards systematic read-across using Generalised Read-Across (GenRA).

作者信息

Patlewicz Grace, Shah Imran

机构信息

Center for Computational Toxicology and Exposure (CCTE), Office of Research and Development, US Environmental Protection Agency, 109 TW Alexander Dr, Research Triangle Park, NC 27711, USA.

出版信息

Comput Toxicol. 2023 Feb;25:1-15. doi: 10.1016/j.comtox.2022.100258.

Abstract

Read-across continues to be a popular data gap filling technique within category and analogue approaches. One of the main issues hindering read-across acceptance is the notion of addressing and reducing uncertainties. Frameworks and formats have been created to help facilitate read-across development, evaluation, and residual uncertainties. However, read-across remains an expert-driven approach with each assessment decided on its own merits with no objective means of evaluating performance or quantifying uncertainties. Here, the underlying motivation of creating an algorithmic approach to read-across, namely the Generalised Read-Across (GenRA) approach, is described. The overall objectives of the approach were to quantify performance and uncertainty. Progress made in quantifying the impact of each similarity context commonly relied upon as part of read-across assessment are discussed. The framework underpinning the approach, the software tools developed to date and how GenRA can be used to make and interpret predictions as part of a screening level hazard assessment decision context are illustrated. Future directions and some of the overarching issues still needed in this field and the extent to which GenRA might facilitate those needs are discussed.

摘要

在类别和类推方法中,交叉参照仍然是一种常用的数据缺口填补技术。阻碍交叉参照被接受的主要问题之一是如何处理和减少不确定性。人们已经创建了一些框架和格式来帮助促进交叉参照的开发、评估以及残余不确定性的处理。然而,交叉参照仍然是一种由专家主导的方法,每次评估都根据其自身优点进行,没有评估性能或量化不确定性的客观方法。在此,将描述创建一种算法化交叉参照方法(即广义交叉参照(GenRA)方法)的潜在动机。该方法的总体目标是量化性能和不确定性。将讨论在量化通常作为交叉参照评估一部分所依赖的每个相似性背景的影响方面取得的进展。将说明该方法的基础框架、迄今开发的软件工具,以及如何将GenRA用作筛选级危害评估决策背景的一部分来进行预测和解释预测。将讨论该领域的未来方向以及仍然需要解决的一些总体问题,以及GenRA在多大程度上可能满足这些需求。

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