A nested mixture model for protein identification using mass spectrometry
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Abstract: Mass spectrometry provides a high-throughput way to identify proteins in biological samples. In a typical experiment, proteins in a sample are first broken into their constituent peptides. The resulting mixture of peptides is then subjected to mass spectrometry, which generates thousands of spectra, each characteristic of its generating peptide. Here we consider the problem of inferring, from these spectra, which proteins and peptides are present in the sample. We develop a statistical approach to the problem, based on a nested mixture model. In contrast to commonly used two-stage approaches, this model provides a one-stage solution that simultaneously identifies which proteins are present, and which peptides are correctly identified. In this way our model incorporates the evidence feedback between proteins and their constituent peptides. Using simulated data and a yeast data set, we compare and contrast our method with existing widely used approaches (PeptideProphet/ProteinProphet) and with a recently published new approach, HSM. For peptide identification, our single-stage approach yields consistently more accurate results. For protein identification the methods have similar accuracy in most settings, although we exhibit some scenarios in which the existing methods perform poorly.
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Cites work
- scientific article; zbMATH DE number 3567782 (Why is no real title available?)
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- Estimating the dimension of a model
- Theory and mathematical methods in bioinformatics
Cited in
(10)- Liquid chromatography mass spectrometry-based proteomics: biological and technological as\-pects
- A graphical model method for integrating multiple sources of genome-scale data
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- A review of statistical methods for protein identification using tandem mass spectrometry
- Protein identification problem from a Bayesian point of view
- Bayesian hierarchical model for protein identifications
- Least Squares Estimators of Peptide Species Concentrations Based on Gaussian Mixture Decompositions of Protein Mass Spectra
- Bayesian nonparametric models for peak identification in MALDI-TOF mass spectroscopy
- Modeling proteolysis from mass spectrometry proteomic data
- Binary Markov random fields and interpretable mass spectra discrimination
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