title: Detecting differential protein expression in large-scale population proteomics.
abstract: BACKGROUND
  Mass spectrometry (MS)-based high-throughput quantitative proteomics shows great potential in large-scale clinical biomarker studies, identifying and quantifying thousands of proteins in biological samples. However, there are unique challenges in analyzing the quantitative proteomics data. One issue is that the quantification of a given peptide is often missing in a subset of the experiments, especially for less abundant peptides. Another issue is that different MS experiments of the same study have significantly varying numbers of peptides quantified, which can result in more missing peptide abundances in an experiment that has a smaller total number of quantified peptides. To detect as many biomarker proteins as possible, it is necessary to develop bioinformatics methods that appropriately handle these challenges.
  
  
  RESULTS
  We propose a Significance Analysis for Large-scale Proteomics Studies (SALPS) that handles missing peptide intensity values caused by the two mechanisms mentioned above. Our model has a robust performance in both simulated data and proteomics data from a large clinical study. Because varying patients' sample qualities and deviating instrument performances are not avoidable for clinical studies performed over the course of several years, we believe that our approach will be useful to analyze large-scale clinical proteomics data.
  
  
  METHODS
  R codes for SALPS are available at http://www.stanford.edu/%7eclairesr/software.html.
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: So Young
authors.initials: SY
authors.lastname: Ryu
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.affiliation: Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Stanford Genome Technology Center, Stanford University, Stanford, CA 94305, USA, Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Xiao
mesh_terms: D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D005786:Gene Expression Regulation; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D010455:Peptides; D011506:Proteins; D020543:Proteome