Assignment of MS-based metabolomic datasets via compound interaction pair mapping

Assignment of physical meaning to mass spectrometry (MS) data peaks is an important scientific challenge for metabolomics investigators. Improvements in instrumental mass accuracy reduce the number of spurious database matches, however, this alone is insufficient for accurate, unique high-throughput assignment. We present a method for clustering MS instrumental artifacts and a stochastic local search algorithm for the automated assignment of large, complex MS-based metabolomic datasets. Artifact peaks and their associated source peaks are grouped into "instrumental clusters." Instrumental clusters, peaks grouped together by shared peak shape in the temporal domain, serve as a guide for the number of assignments necessary to completely explain a given dataset. We refine mass only assignments through the intersection of peak correlation pairs with a database of biochemically relevant interaction pairs. Further refinement is achieved through a stochastic local search optimization algorithm that selects individual assignments for each instrumental cluster. The algorithm works by choosing the peak assignment that maximally explains the connectivity of a given cluster. We demonstrate that this methodology provides a significant advantage over standard methods for the assignment of metabolites in a UPLC-MS diabetes dataset.