Building a map of the breast cancer proteome - Strategies to increase coverage

Abstract: Amongst the various –omics sciences, proteomics has the highest potential for functional characterization and consequently can contribute significantly to the field of cancer research. In particular, the focus of this thesis is on breast cancer. Alas, since state-of-the-art technologies cannot meet the complexity of upper eukaryotic proteomes, a complete resolution of clinical samples is still unachievable. Comprehensive mapping of proteins involved in cancer and of their PTMs is proposed in this thesis as a general strategy to increase the output of mass-spectrometry based proteomics. Different approaches to improve the coverage of this map are proposed: optimization of sample fractionation, focusing on difficult sub-proteomes, targeting of specific biological processes and optimization of data analysis. A combination of these approaches will provide a growing collection of empirical MS-spectra, which will enhance the detection by shotgun proteomics and facilitate the transition towards the development of targeted assays.