Identifying the unknowns: towards structural elucidation of small molecules using mass spectrometry

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Rapid identification of small compounds from small amounts of substance is of interest in many areas of biology and medicine such as metabolomics, bio-prospecting, biomarker discovery, and diagnostics. Today, mass spectrometry (MS) is a key technology for the identification of small molecules. Due to immense technological advances in mass spectrometry over the last years, the amount and complexity of MS data has been growing rapidly. Tandem mass spectrometry offers the potential of identifying small molecules solely from MS fingerprints, but computational analysis of such data is in its infancy, and this is presumed to be one of the major technological hurdles in metabolomics today. The key objective of this project is to develop computational methods to “identify the unknowns”, that is, compounds that cannot be found in any database. For this, we will develop new computational techniques, models, and algorithms for the interpretation of MS fragmentation data from small molecules. As a medium term goal, we want to develop a BLAST-like search tool for searching fragmentation patterns. It turns out that many of the arising problems are computationally hard, and require new algorithmic concepts to guarantee that optimal solutions can be found. We will implement, train, and evaluate our methods to allow an automated processing of metabolite MS data. Prof. Stephan Clemens (Bayreuth University) and Dr. Christoph Böttcher (IPB Halle) plan to apply for funding to study genetic control of secondary metabolism at a genomewide scale, employing A. thaliana populations developed for association mapping. We plan to closely cooperate with their groups on the subject matter.