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Biological Systems Analysis by a Network Proteomics Approach and Subcellular protein Profiling

We provide a systematic analysis of a biological system, the microbial pathogen Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and biocomputational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane and cytosol) of Mtb. We report the compartmentalization of 1,044 identified proteins using proteomics methods. Genome-based biological network analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.