重新调查基于诱的假发现率控制在蛋白质学中的正确性
Jack Freestone1, William Stafford Noble2,3, Uri Keich1
1School of Mathematics and Statistics F07, University of Sydney, New South Wales 2006, Australia.
Journal of proteome research
|April 30, 2024
概括
蛋白质组学中的开放修改搜索可能会因错误发现率 (FDR) 控制问题而夸大发现. 重新分析表明,标准的FDR控制方法对于自下而上的蛋白质组学协同质谱 (MS/MS) 数据是可靠的.
科学领域:
- 蛋白质组学是指蛋白质组学.
- 质谱测量质量谱测量
- 生物信息学是一种生物信息学.
背景情况:
- 使用双重质谱 (MS/MS) 的自下而上的蛋白质组学依赖于数据库搜索.
- 传统方法难以检测具有翻译后修饰 (PTM) 的.
- 开放的修改搜索放松了质量匹配,以识别更广泛的PTM.
研究的目的:
- 实证地调查公开修改搜索提供比传统狭窄窗口搜索更高的统计能力的说法.
- 在常用的后处理工具中识别虚假发现率 (FDR) 控制的潜在问题.
主要方法:
- 现有蛋白质组学MS/MS数据的经验再分析.
- 开放修改搜索结果与传统狭窄窗口搜索结果的比较.
- 应用基于竞争的标准目标诱FDR控制.
主要成果:
- 在机器学习后处理器 (Percolator,PeptideProphet) 中发现了FDR控制的潜在一般问题.
- 在考虑了模拟光谱和候选数量差异后,数据不支持固有的FDR控制问题.
- 有证据表明,对于MS/MS数据库搜索,标准的FDR控制通常是强大的.
结论:
- 对于开放式修改搜索的优越统计能力的最初要求可能受到FDR控制器件的影响.
- 标准的FDR控制方法对于自下而上的蛋白质组学MS/MS数据分析似乎可靠.
- 考虑到特定的搜索参数,对开放式修改搜索中的FDR控制进行进一步调查是有必要的.
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