title: The human plasma proteome: a nonredundant list developed by combination of four separate sources.
abstract: We have merged four different views of the human plasma proteome, based on different methodologies, into a single nonredundant list of 1175 distinct gene products. The methodologies used were 1) literature search for proteins reported to occur in plasma or serum; 2) multidimensional chromatography of proteins followed by two-dimensional electrophoresis and mass spectroscopy (MS) identification of resolved proteins; 3) tryptic digestion and multidimensional chromatography of peptides followed by MS identification; and 4) tryptic digestion and multidimensional chromatography of peptides from low-molecular-mass plasma components followed by MS identification. Of 1,175 nonredundant gene products, 195 were included in more than one of the four input datasets. Only 46 appeared in all four. Predictions of signal sequence and transmembrane domain occurrence, as well as Genome Ontology annotation assignments, allowed characterization of the nonredundant list and comparison of the data sources. The "nonproteomic" literature (468 input proteins) is strongly biased toward signal sequence-containing extracellular proteins, while the three proteomics methods showed a much higher representation of cellular proteins, including nuclear, cytoplasmic, and kinesin complex proteins. Cytokines and protein hormones were almost completely absent from the proteomics data (presumably due to low abundance), while categories like DNA-binding proteins were almost entirely absent from the literature data (perhaps unexpected and therefore not sought). Most major categories of proteins in the human proteome are represented in plasma, with the distribution at successively deeper layers shifting from mostly extracellular to a distribution more like the whole (primarily cellular) proteome. The resulting nonredundant list confirms the presence of a number of interesting candidate marker proteins in plasma and serum.
authors.affiliation: The Plasma Proteome Institute, Washington DC 20009-3450, USA. leighanderson@plasmaproteome.org
authors.forename: N Leigh
authors.initials: NL
authors.lastname: Anderson
authors.forename: Malu
authors.initials: M
authors.lastname: Polanski
authors.forename: Rembert
authors.initials: R
authors.lastname: Pieper
authors.forename: Tina
authors.initials: T
authors.lastname: Gatlin
authors.forename: Radhakrishna S
authors.initials: RS
authors.lastname: Tirumalai
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
authors.forename: Joel G
authors.initials: JG
authors.lastname: Pounds
authors.forename: Richard
authors.initials: R
authors.lastname: Fagan
authors.forename: Anna
authors.initials: A
authors.lastname: Lobley
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001798:Blood Proteins / Q000032:analysis*; D019295:Computational Biology; D016206:Databases, Bibliographic; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000032:analysis; D010449:Peptide Mapping / Q000379:methods; D010949:Plasma / Q000737:chemistry*; D020543:Proteome / Q000737:chemistry*; D014357:Trypsin / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D010446:Peptide Fragments; D020543:Proteome; D014357:Trypsin