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Accurately Assigning Peptides to Spectra When Only a Subset of Peptides Are Relevant.

ABSTRACT: The standard proteomics database search strategy involves searching spectra against a peptide database and estimating the false discovery rate (FDR) of the resulting set of peptide-spectrum matches. One assumption of this protocol is that all the peptides in the database are relevant to the hypothesis being investigated. However, in settings where researchers are interested in a subset of peptides, alternative search and FDR control strategies are needed. Recently, two methods were proposed to address this problem: subset-search and all-sub. We show that both methods fail to control the FDR. For subset-search, this failure is due to the presence of "neighbor" peptides, which are defined as irrelevant peptides with a similar precursor mass and fragmentation spectrum as a relevant peptide. Not considering neighbors compromises the FDR estimate because a spectrum generated by an irrelevant peptide can incorrectly match well to a relevant peptide. Therefore, we have developed a new method, "subset-neighbor search" (SNS), that accounts for neighbor peptides. We show evidence that SNS controls the FDR when neighbors are present and that SNS outperforms group-FDR, the only other method that appears to control the FDR relative to a subset of relevant peptides.

SUBMITTER: Lin A

PROVIDER: S-EPMC8489664 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Accurately Assigning Peptides to Spectra When Only a Subset of Peptides Are Relevant.

Lin Andy A Plubell Deanna L DL Keich Uri U Noble William S WS

Journal of proteome research 20210708 8

The standard proteomics database search strategy involves searching spectra against a peptide database and estimating the false discovery rate (FDR) of the resulting set of peptide-spectrum matches. One assumption of this protocol is that all the peptides in the database are relevant to the hypothesis being investigated. However, in settings where researchers are interested in a subset of peptides, alternative search and FDR control strategies are needed. Recently, two methods were proposed to a ...[more]

PMID: 34236864

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Accurately Assigning Peptides to Spectra When Only a Subset of Peptides Are Relevant.

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Accurately Assigning Peptides to Spectra When Only a Subset of Peptides Are Relevant.

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