Abstract
BackgroundMass 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.ResultsWe 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.ConclusionsFor 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.
Highlights
Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery
We show that the problem of selecting the minimal set of Triple X proteomics’-strategy (TXP)-antigens is equivalent to the set cover problem
Starting from the real-world lab engineering task, we have shown that the problem of choosing a minimal set of epitopes is equivalent to the well-known set cover problem
Summary
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. MRNA-Profiling is based on hybridization of DNAmolecules 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. 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
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