Computational analysis of mass spectrometric data for whole organism proteomic studies

by 1977- Razumovski, Evgenia

In the last decades great breakthroughs have been achieved in the study of the genomes, supplying us with the vast knowledge of the genes and a large number of sequenced organisms. With the availability of genome information, the new systematic studies have arisen. One of the most prominent areas is proteomics. Proteomics is a discipline devoted to the study of the organism’s expressed protein content. Proteomics studies are concerned with a wide range of problems. Some of the major proteomics focuses upon the studies of protein expression patterns, the detection of protein-protein interactions, protein quantitation, protein localization analysis, and characterization of post-translational modifications. The emergence of proteomics shows great promise to furthering our understanding of the cellular processes and mechanisms of life. One of the main techniques used for high-throughput proteomic studies is mass spectrometry. Capable of detecting masses of biological compounds in complex mixtures, it is currently one of the most powerful methods for protein characterization. New horizons are opening with the new developments of mass spectrometry instrumentation, which can now be applied to a variety of proteomic problems. One of the most popular applications of proteomics involves whole organism high-throughput experiments. However, as new instrumentation is being developed, followed by the design of new experiments, we find ourselves needing new computational algorithms to interpret the results of the experiments. As the thresholds of the current technology are being probed, the new algorithmic designs are beginning to emerge to meet the challenges of the mass spectrometry data evaluation and interpretation. ii This dissertation is devoted to computational analysis of mass spectrometric data, involving a combination of different topics and techniques to improve our understanding of biological processes using high-throughput whole organism proteomic studies. It consists of the development of new algorithms to improve the data interpretation of the current tools, introducing a new algorithmic approach for post-translational modification detection, and the characterization of a set of computational simulations for biological agent detection in a complex organism background. These studies are designed to further the capabilities of understanding the results of high-throughput mass spectrometric experiments and their impact in the field of proteomics. iii