title: Efficient marginalization to compute protein posterior probabilities from shotgun mass spectrometry data.
abstract: The problem of identifying proteins from a shotgun proteomics experiment has not been definitively solved. Identifying the proteins in a sample requires ranking them, ideally with interpretable scores. In particular, "degenerate" peptides, which map to multiple proteins, have made such a ranking difficult to compute. The problem of computing posterior probabilities for the proteins, which can be interpreted as confidence in a protein's presence, has been especially daunting. Previous approaches have either ignored the peptide degeneracy problem completely, addressed it by computing a heuristic set of proteins or heuristic posterior probabilities, or estimated the posterior probabilities with sampling methods. We present a probabilistic model for protein identification in tandem mass spectrometry that recognizes peptide degeneracy. We then introduce graph-transforming algorithms that facilitate efficient computation of protein probabilities, even for large data sets. We evaluate our identification procedure on five different well-characterized data sets and demonstrate our ability to efficiently compute high-quality protein posteriors.
authors: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors: Oliver
authors: O
authors: Serang
authors: Michael J
authors: MJ
authors: MacCoss
authors: William Stafford
authors: WS
authors: Noble
mesh_terms: D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D001499:Bayes Theorem; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000032:analysis; D006193:Haemophilus influenzae / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D011336:Probability; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins