False discovery rate estimation using candidate peptides for each spectrum

BMC Bioinformatics

卷:23

Research

Hyunwoo Kim¹  Sangjeong Lee²  Heejin Park² 

[1] Biomedical Informatics Team, Korea Institute of Science and Technology Information, 34141, Daejeon, Republic of Korea;

[2] Department of Computer Science, Hanyang University, 06978, Seoul, Republic of Korea;

关键词: Target-decoy strategy;    False discovery rate;    Proteomics;    Tandem mass spectrometry;   

DOI  :  10.1186/s12859-022-05002-4

 received in 2022-05-12, accepted in 2022-10-25,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundFalse discovery rate (FDR) estimation is very important in proteomics. The target-decoy strategy (TDS), which is often used for FDR estimation, estimates the FDR under the assumption that when spectra are identified incorrectly, the probabilities of the spectra matching the target or decoy peptides are identical. However, no spectra matching target or decoy peptide probabilities are identical. We propose cTDS (target-decoy strategy with candidate peptides) for accurate estimation of the FDR using the probability that the spectrum is identified incorrectly as a target or decoy peptide.ResultsMost spectrum cases result in a probability of having the spectrum identified incorrectly as a target or decoy peptide of close to 0.5, but only about 1.14–4.85% of the total spectra have an exact probability of 0.5. We used an entrapment sequence method to demonstrate the accuracy of cTDS. For fixed FDR thresholds (1–10%), the false match rate (FMR) in cTDS is closer than the FMR in TDS. We compared the number of peptide-spectrum matches (PSMs) obtained with TDS and cTDS at a 1% FDR threshold with the HEK293 dataset. In the first and third replications, the number of PSMs obtained with cTDS for the reverse, pseudo-reverse, shuffle, and de Bruijn databases exceeded those obtained with TDS (about 0.001–0.132%), with the pseudo-shuffle database containing less compared to TDS (about 0.05–0.126%). In the second replication, the number of PSMs obtained with cTDS for all databases exceeds that obtained with TDS (about 0.013–0.274%).ConclusionsWhen spectra are actually identified incorrectly, most probabilities of the spectra matching a target or decoy peptide are not identical. Therefore, we propose cTDS, which estimates the FDR more accurately using the probability of the spectrum being identified incorrectly as a target or decoy peptide.

【 授权许可】

CC BY   
© The Author(s) 2022

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