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arXiv · 1501.00537

A theoretical foundation of the target-decoy search strategy for false discovery rate control in proteomics

Kun He·Yan Fu·Wen-Feng Zeng·Lan Luo·Hao Chi·Chao Liu·Lai-Yun Qing·Rui-Xiang Sun·Si-Min He
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Abstract

Motivation: Target-decoy search (TDS) is currently the most popular strategy for estimating and controlling the false discovery rate (FDR) of peptide identifications in mass spectrometry-based shotgun proteomics. While this strategy is very useful in practice and has been intensively studied empirically, its theoretical foundation has not yet been well established. Result: In this work, we systematically analyze the TDS strategy in a rigorous statistical sense. We prove that the commonly used concatenated TDS provides a conservative estimate of the FDR for any given score threshold, but it cannot rigorously control the FDR. We prove that with a slight modification to the commonly used formula for FDR estimation, the peptide-level FDR can be rigorously controlled based on the concatenated TDS. We show that the spectrum-level FDR control is difficult. We verify the theoretical conclusions with real mass spectrometry data.

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Kun He, Yan Fu, Wen-Feng Zeng, Lan Luo, Hao Chi, Chao Liu, Lai-Yun Qing, Rui-Xiang Sun, Si-Min He. 2015-01-03. A theoretical foundation of the target-decoy search strategy for false discovery rate control in proteomics. https://arxiv.org/abs/1501.00537

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