Paramounter: Direct Measurement of Universal Parameters To Process Metabolomics Data in a “White Box”

Choosing appropriate data processing parameters is critical in processing liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics data. The conventional design of experiments (DOE) approach is time-consuming and provides no intuitive explanation why the selected parameters generate the best results. After studying commonly used metabolomics data processing software, this work summarized a set of universal parameters, including mass tolerance, peak height, peak width, and instrumental shift. These universal parameters are shared among different feature extraction programs and are critical to metabolic feature extraction. We then developed Paramounter, an R program that automatically measures these universal parameters from raw LC-MS-based metabolomics data prior to metabolic feature extraction. This is made possible through novel concepts of rank-based intensity sorting, zone of interest, and many others. Paramounter also translates universal parameters to software-specific parameters for data processing in different programs. Applying Paramounter is demonstrated to provide a threefold increase in the extracted metabolites compared to using default parameters in MS-DIAL-based feature extraction. Furthermore, the comparison between Paramounter, AutoTuner, and IPO showed that Paramounter generates 3.7- and 1.6-fold more true positive features than AutoTuner and IPO, respectively. Further validation of Paramounter on 11 datasets covering different sample types, data acquisition modes, and MS vendors proved that Paramounter is a convenient and robust program. Overall, the proposed universal parameters and the development of Paramounter address a critical need in metabolomics data processing, transforming metabolomics feature extraction from a "black box" to a "white box." Paramounter is freely available on GitHub (https://github.com/HuanLab/Paramounter).