Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry

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.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.Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. Contrary to the analysis of mRNA profiles, the screening of protein expression profiles allows direct conclusions about the molecular mechanisms involved in a certain condition, because many cellular processes are directly related to the protein functions.mRNA-Profiling is based on hybridization of DNA-molecules and binding molecules are easy to postulate and to synthesize. This allows the comparatively cheap production of high-density microarrays that cover a large portion of the known genome. Unfortunately this is not applicable in the protein world since features of protein binding molecules can not be predicted as easily.Mass spectrometry allows a parallel, high-throughput detection of a mixture containing a limited number of peptides [1-3]. For qualitative and quantitative protein profiling of a complex sample time-consuming sample fractionation steps such as 2D gel electrophoresis or multidimensional chromatography are necessary. In this way, small subsets of the sample are analyzed fraction by fraction. The mentioned fractionation methods are the limiting factor in MS-based protein analysis.Immunoaffinity-MS approaches combine antibody-based approaches with mass-spectrometry, increasing sample throughput and detection sensitivity by capturing proteins or peptides from the sample using protein-or peptide-specific antibodies [4-9]. However, the drawb