Bioinformatics Algorithms and Software for Proteomics

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Proteomics aims to study all proteins in an organism, and is reshaping the health research and pharmaceutical industry. One important application of proteomics is the discovery of protein biomarkers that can be used for disease diagnoses and personalized medicine. The biomarkers also become excellent drug targets. One of the most active areas in cancer treatment today is the antibody-drug conjugates that use an antibody to recognize the biomarkers on the surface of cancer cells, and deliver the drug specifically to the cancer cells.******Mass spectrometry has become the primary method in proteomics for protein characterization. One mass spectrometry experiment can produce up to millions of mass spectra. Then, sophisticated computer algorithms are used to analyze the data and find out the proteins' identities, primary sequences, post-translational modifications (PTM), single amino acid polymorphisms (SAP), as well as quantities.******My proposed research program aims to develop the algorithms and software tools that facilitate the in-depth proteome characterization using mass spectrometry. Many of these tools will enable new capabilities for proteomics. In particular, the ultimate long-term goal of this research program is to enable the whole proteome sequencing, where all abundant proteins in a proteome, including the PTM and SAP, can be sequenced de novo in a high-throughput mass spectrometry experiment. The breakthrough will likely come from a joint innovation that involves a vast improvement of spectrometers, a novel experimental design, and innovative computer algorithms. The achievement of this goal will fundamentally change the way scientists conduct biological and health researches – just like how genome sequencing did in the past two decades. My research group has accumulated significant expertise and built a broad collaboration network with mass spectrometry labs and industrial partners. This puts us at a good position in making critical contributions to the whole proteome sequencing goal. The success will strengthen Canada's leading position in the international proteomics research.******The proteome sequencing goal may carry beyond the proposed renewal term of this NSERC Discovery program. By the end of the proposed term, we expect to have a method that can routinely de novo sequence a purified protein with mass spectrometry in minutes. This already has a profound impact to the whole proteomics field and pharmaceutical industry. Other shorter term goals include real-time PTM and SAP detection, protein quantification, as well as making the mass spectrometers smarter by result-dependent acquisition.******The accomplishment of these goals will inevitably require the participation of many talented graduate students. Many HQP will be trained in a cross-disciplinary environment. I envision that many of them will contribute innovative ideas, and grow to be independent researchers in the end.