Development of real-time control methodologies for tandem mass spectrometry

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One of the most important goals in the early detection of genomic-related disease, and the discovery ofassociated biomarkers, is to identify and characterize the proteins and protein complexes present in related celllines. Tandem mass spectrometry (MS/MS) is a powerful tool for identifying and comparing the proteinsexpressed in complex biological systems. However, the performance of mass spectrometers remains limited interms of the proportion of MS/MS data that can actually be interpreted. For example, up to 70% of the peptideMS/MS spectra generated by quadrupole-time of flight mass spectrometers, and up to 85% of those producedby ion trapping instruments, cannot be interpreted using any available technique. Furthermore, a great deal oftime is wasted in acquiring and attempting to interpret these poor-quality spectra. Based on our experience,literature review, and conversations with industry, it is apparent that the main obstacle to improvingperformance in protein mass spectrometry is the lack of fast, efficient algorithms capable of real-time detectionand/or selection of target peptide ions for fragmentation and MS/MS analysis. The goal of the proposedresearch is to overcome this challenge, and hence, increase throughput and efficiency for protein massspectrometry. This will be achieved by developing (a) an efficient algorithm for assessing the quality of peptideMS/MS spectra, and (b) a fast and accurate algorithm for on-line protein identification using verified peptideMS/MS spectra. The proposed research will significantly improve the performance of mass spectrometers byenabling the development of real-time control methodologies based upon the algorithms developed in thisproposal. In providing such advanced methodologies for high-throughput identification of proteins and proteinbiomarkers, this project will also make a major contribution to Canadian health research, while promotingacademic, industrial economic activity in Canada.