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A
Non-Redundant List of Proteins Present in Plasma
In
a recent paper,
we examined the properties of a "consensus" human
plasma proteome created by merging four different datasets,
based on different methodologies,
into a single non-redundant 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 2-D electrophoresis and 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 weight plasma components
followed by MS identification. Of 1175 non-redundant gene
products, 195 were included in more than one of the four
input data sets. Only 46 appeared in all four. Predictions
of signal sequence and transmembrane domain occurrence,
as well as Genome Ontology (GO) annotation assignments,
allowed characterization of the non-redundant list and comparison
of the data sources. The “nonproteomic” literature
(468 input proteins) is strongly biased towards 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., and provides a starting
point for development of specific assays for panel validation
(e.g., using SISCAPA technology).
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The Human Plasma
Proteome: A Non-Redundant List Developed by Combination
of Four Separate Sources. Anderson, N.L., Polanski, M.,
Pieper, R., Gatlin, T., Tirumalai, R.S., Conrads, T.P.,
Veenstra, T.D., Adkins, J.N., Pounds, J.G, Fagan, R., and
Lobley, A., Molecular & Cellular Proteomics, in press
(2004).
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