BACKGROUND: Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency.RESULTS:We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties.CONCLUSIONS:For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.
@article{Planatscher2010,
author = {Planatscher, Hannes and Supper, Jochen and Poetz, Oliver and Stoll,
Dieter and Joos, Thomas and Templin, Markus and Zell, Andreas},
title = {Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry},
journal = {Algorithms for Molecular Biology},
year = {2010},
volume = {5},
pages = {28},
number = {1},
month = jun,
abstract = {BACKGROUND: Mass spectrometry (MS) based protein profiling has become
one of the key technologies in biomedical research and biomarker
discovery. One bottleneck in MS-based protein analysis is sample
preparation and an efficient fractionation step to reduce the complexity
of the biological samples, which are too complex to be analyzed directly
with MS. Sample preparation strategies that reduce the complexity
of tryptic digests by using immunoaffinity based methods have shown
to lead to a substantial increase in throughput and sensitivity in
the proteomic mass spectrometry approach. The limitation of using
such immunoaffinity-based approaches is the availability of the appropriate
peptide specific capture antibodies. Recent developments in these
approaches, where subsets of peptides with short identical terminal
sequences can be enriched using antibodies directed against short
terminal epitopes, promise a significant gain in efficiency.RESULTS:We
show that the minimal set of terminal epitopes for the coverage of
a target protein list can be found by the formulation as a set cover
problem, preceded by a filtering pipeline for the exclusion of peptides
and target epitopes with undesirable properties.CONCLUSIONS:For small
datasets (a few hundred proteins) it is possible to solve the problem
to optimality with moderate computational effort using commercial
or free solvers. Larger datasets, like full proteomes require the
use of heuristics.},
doi = {10.1186/1748-7188-5-28},
isbn = {1748-7188},
url = {http://www.almob.org/content/5/1/28}
}