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Tutorial: best practices and considerations for mass-spectrometry-based protein biomarker discovery and validation
Nature Protocols ( IF 13.1 ) Pub Date : 2021-07-09 , DOI: 10.1038/s41596-021-00566-6
Ernesto S Nakayasu 1 , Marina Gritsenko 1 , Paul D Piehowski 1 , Yuqian Gao 1 , Daniel J Orton 1 , Athena A Schepmoes 1 , Thomas L Fillmore 1 , Brigitte I Frohnert 2 , Marian Rewers 2 , Jeffrey P Krischer 3 , Charles Ansong 1 , Astrid M Suchy-Dicey 4 , Carmella Evans-Molina 5 , Wei-Jun Qian 1 , Bobbie-Jo M Webb-Robertson 1, 6 , Thomas O Metz 1
Affiliation  

Mass-spectrometry-based proteomic analysis is a powerful approach for discovering new disease biomarkers. However, certain critical steps of study design such as cohort selection, evaluation of statistical power, sample blinding and randomization, and sample/data quality control are often neglected or underappreciated during experimental design and execution. This tutorial discusses important steps for designing and implementing a liquid-chromatography–mass-spectrometry-based biomarker discovery study. We describe the rationale, considerations and possible failures in each step of such studies, including experimental design, sample collection and processing, and data collection. We also provide guidance for major steps of data processing and final statistical analysis for meaningful biological interpretations along with highlights of several successful biomarker studies. The provided guidelines from study design to implementation to data interpretation serve as a reference for improving rigor and reproducibility of biomarker development studies.



中文翻译:


教程:基于质谱的蛋白质生物标志物发现和验证的最佳实践和注意事项



基于质谱的蛋白质组分析是发现新疾病生物标志物的有效方法。然而,研究设计的某些关键步骤,如队列选择、统计功效评估、样本盲法和随机化以及样本/数据质量控制,在实验设计和执行过程中经常被忽视或低估。本教程讨论设计和实施基于液相色谱-质谱法的生物标志物发现研究的重要步骤。我们描述了此类研究每个步骤的基本原理、考虑因素和可能的失败,包括实验设计、样本收集和处理以及数据收集。我们还为数据处理和最终统计分析的主要步骤提供指导,以实现有意义的生物学解释,以及几项成功的生物标志物研究的亮点。所提供的从研究设计到实施再到数据解释的指南可作为提高生物标志物开发研究的严谨性和可重复性的参考。

更新日期:2021-07-12
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