Clusterwise Peak Detection and Filtering Based on Spatial Distribution To Efficiently Mine Mass Spectrometry Imaging Data

[Image: see text] Mass spectrometry imaging (MSI) has the potential to reveal the localization of thousands of biomolecules such as metabolites and lipids in tissue sections. The increase in both mass and spatial resolution of today’s instruments brings on considerable challenges in terms of data processing; accurately extracting meaningful signals from the large data sets generated by MSI without losing information that could be clinically relevant is one of the most fundamental tasks of analysis software. Ion images of the biomolecules are generated by visualizing their intensities in 2-D space using mass spectra collected across the tissue section. The intensities are often calculated by summing each compound’s signal between predefined sets of borders (bins) in the m/z dimension. This approach, however, can result in mixed signals from different compounds in the same bin or splitting the signal from one compound between two adjacent bins, leading to low quality ion images. To remedy this problem, we propose a novel data processing approach. Our approach consists of a sensitive peak detection method able to discover both faint and localized signals by utilizing clusterwise kernel density estimates (KDEs) of peak distributions. We show that our method can recall more ground-truth molecules, molecule fragments, and isotopes than existing methods based on binning. Furthermore, it automatically detects previously reported molecular ions of lipids, including those close in m/z, in an experimental data set.