Assigning significance in label-free quantitative proteomics to include single-peptide-hit proteins with low replicates.
Assigning significance in label-free quantitative proteomics to include single-peptide-hit proteins with low replicates.
复制标题
在无标记定量蛋白质组学中赋予重要性，以包括具有低重复次数的单肽命中蛋白质。
DOI：
10.1155/2010/731582
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Li,Qingbo
中科院分区：
文献类型：
--
作者：
Li,Qingbo
当在无标记蛋白质组学实验中样本重复受到限制时，对于具有单肽命中或小倍数变化的蛋白质来说，选择具有统计显着性的差异调节蛋白质仍然很困难。本文旨在解决这个问题。这里采用的方法的一个重要组成部分是利用最小排列重要配对数 (MPSP) 规则来减少误报。 MPSP 规则从有限的分析重复中生成排列的样本配对，并且仅要求只有当发现差异调节的蛋白质在指定数量的排列的样本配对中具有显着性时才能选择差异调节的蛋白质。具有信噪比统计量的幂律全局误差模型（PLGEM-STN）和恒定倍数变化阈值最初都用于选择差异调节蛋白。但本研究发现这两种方法都不够严格，无法将错误发现率控制在 5% 以内。另一方面，MPSP 规则与这两种方法中的任何一种的组合显着减少了假阳性，对选择差异调节蛋白质（包括具有单肽命中或变化 <2 倍的蛋白质）的敏感性几乎没有影响。
When sample replicates are limited in a label‐free proteomics experiment, selecting differentially regulated proteins with an assignment of statistical significance remains difficult for proteins with a single‐peptide hit or a small fold‐change. This paper aims to address this issue. An important component of the approach employed here is to utilize the rule of Minimum number of Permuted Significant Pairings (MPSP) to reduce false positives. The MPSP rule generates permuted sample pairings from limited analytical replicates and simply requires that a differentially regulated protein can be selected only when it is found significant in designated number of permuted sample pairings. Both a power law global error model with a signal‐to‐noise ratio statistic (PLGEM‐STN) and a constant fold‐change threshold were initially used to select differentially regulated proteins. But both methods were found not stringent enough to control the false discovery rate to 5% in this study. On the other hand, the combination of the MPSP rule with either of these two methods significantly reduces false positives with little effect on the sensitivity to select differentially regulated proteins including those with a single‐peptide hit or with a <2‐fold change.