Petrick Lauren M, Achaintre David, Maroli Amith, Landero Julio, Dessanayake Priyanthi S, Teitelbaum Susan L, Wolff Mary S, Arora Manish, Wright Robert O, Andra Syam S
Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Institute for Exposomics Research, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Environ Health Perspect. 2025 May;133(5):55001. doi: 10.1289/EHP15465. Epub 2025 May 12.
Innovation in mass spectrometry-based methods to both quantify and perform discovery has blurred the lines between targeted and untargeted assays of biospecimens. Continuous data-concentrations or intensity values generated from both methods-can be used in statistical analysis to determine associations with health outcomes, but concentration values are needed to compare measurements from one study to another to inform policy making decisions and to develop clinically relevant thresholds. As a single solution for discovery and quantitation, new hybrid-type assays derive concentration values for chemicals or metabolites but with varying degrees of uncertainty that may be greater than traditional quantitative assays. There is no current single standard to guide reporting bioassay concentrations or their uncertainty in concentration values from hybrid assays. Even when measures are robust, obtained with high scientific rigor, and provide valuable data toward risk assessment, unknown uncertainty can lead to bias in interpretation of reported data or omission of reported data that does not meet the strict criteria for absolute quantitation.
The objective of this commentary is to articulate a scheme that enables investigators across bioanalytical fields to easily report analyte measurement assurance on the same scale from quantitative, untargeted, or hybrid assays that include a range of concentration confidences.
We propose a simple scheme to report concentrations for targeted and untargeted analytes. Level 1 is a confirmed concentration following established tolerances in a fully quantitative assay while level 5 is a tentative intensity from a typical untargeted assay. This framework enables easy communication of uncertainty in concentration measurements to aid cross-validation, meta-analysis, and extrapolation across studies. It will facilitate interpretation while supporting analytical advancement and allow clear and concise measurement reporting across a broad range of confidences. https://doi.org/10.1289/EHP15465.
基于质谱的定量和发现方法的创新模糊了生物样本靶向分析和非靶向分析之间的界限。这两种方法产生的连续数据（浓度或强度值）可用于统计分析，以确定与健康结果的关联，但需要浓度值来比较不同研究的测量结果，为政策制定决策提供信息，并制定临床相关阈值。作为发现和定量的单一解决方案，新的混合型分析可得出化学物质或代谢物的浓度值，但其不确定程度各不相同，可能大于传统定量分析。目前没有单一标准来指导报告生物分析浓度或混合型分析浓度值的不确定性。即使测量结果可靠、科学严谨且能为风险评估提供有价值的数据，但未知的不确定性仍可能导致对报告数据的解释出现偏差，或遗漏不符合绝对定量严格标准的报告数据。
本评论的目的是阐明一种方案，使生物分析领域的研究人员能够轻松地在同一尺度上报告来自定量、非靶向或混合型分析（包括一系列浓度置信度）的分析物测量保证。
我们提出了一个简单的方案来报告靶向和非靶向分析物的浓度。一级是在完全定量分析中遵循既定公差的确认浓度，而五级是典型非靶向分析的暂定强度。该框架便于传达浓度测量中的不确定性，以帮助进行交叉验证、荟萃分析和跨研究推断。它将有助于解释，同时支持分析进步，并允许在广泛的置信度范围内进行清晰简洁的测量报告。https://doi.org/10.1289/EHP15465。
