An automated, sheathless capillary electrophoresis-mass spectrometry
platform for discovery of biomarkers in human serum.
Alexander P.Sassi, Frank Andel , Hans-Marcus L.Bitter, Michael P.S.Brown,
Robert G.Chapman, Jeraldine Espiritu, Alfred C.Greenquist, Isabelle Guyon,
Mariana Horchi-Alegre, Kathy L.Stults, Ann Wainright, Jonathan C.Heller, John
T.Stults. Electrophoresis 26, 2005.
A capillary electrophoresis-mass spectrometry (CE-MS)method has been developed
to perform routine,automated analysis of low-molecular-weight peptides in
human serum.The method incorporates transient isotachophoresis for in-line
preconcentra-
tion and a sheathless electrospray interface.To evaluate the performance
of the method and demonstrate the utility of the approach,an experiment was
designed in which peptides were added to sera from individuals at each of
two different con-
centrations,artificially creating two groups of samples.The CE-MS data from
the serum samples were divided into separate training and test sets.A pattern-recognition/feature-selection
algorithm based on support vector machines was used to select
the mass-to-charge (m/z )values from the training set data that distinguished
the two groups of samples from each other.The added peptides were identified
correctly as the distinguishing features,and pattern recognition based on
these peptides was used
to assign each sample in the independent test set to its respective group.A
twofold difference in peptide concentration could be detected with statistical
significance (pvalue ,0.0001).The accuracy of the assignment was 95%,demonstrating
the utility of
this technique for the discovery of patterns of biomarkers in serum.
Keywords:Biomarkers /Capillary electrophoresis /Serum /Sheathless
electrospray /Time of flight-mass spectrometry
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