title: Direct maximization of protein identifications from tandem mass spectra.
abstract: The goal of many shotgun proteomics experiments is to determine the protein complement of a complex biological mixture. For many mixtures, most methodological approaches fall significantly short of this goal. Existing solutions to this problem typically subdivide the task into two stages: first identifying a collection of peptides with a low false discovery rate and then inferring from the peptides a corresponding set of proteins. In contrast, we formulate the protein identification problem as a single optimization problem, which we solve using machine learning methods. This approach is motivated by the observation that the peptide and protein level tasks are cooperative, and the solution to each can be improved by using information about the solution to the other. The resulting algorithm directly controls the relevant error rate, can incorporate a wide variety of evidence and, for complex samples, provides 18-34% more protein identifications than the current state of the art approaches.
authors: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors: Marina
authors: M
authors: Spivak
authors: Jason
authors: J
authors: Weston
authors: Daniela
authors: D
authors: Tomazela
authors: Michael J
authors: MJ
authors: MacCoss
authors: William Stafford
authors: WS
authors: Noble
mesh_terms: D000465:Algorithms; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism; D001185:Artificial Intelligence; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D045424:Complex Mixtures / Q000032:analysis*; D030562:Databases, Protein; D006801:Humans; D057045:Laryngopharyngeal Reflux; D015233:Models, Statistical; D010446:Peptide Fragments / Q000032:analysis; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012984:Software; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D029742:Caenorhabditis elegans Proteins; D045424:Complex Mixtures; D010446:Peptide Fragments; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins