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

Abstract

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).

Addressing big data challenges in mass spectrometry-based metabolomics

“…These concepts were then implemented into Paramounter, an R program that automatically and accurately extracts the distributions of these universal parameters from the raw LC-MS-based metabolomics data before feature extraction. 14 Our results showed that Paramounter-based direct measurement of feature extraction parameters performs better than conventional DOE-based approaches. It is also more efficient and convenient to use.…”

Mechanistic Understanding of the Discrepancies between Common Peak Picking Algorithms in Liquid Chromatography–Mass Spectrometry-Based Metabolomics

“…Paramounter was used to optimize the data processing parameters for each dataset in each peak picking algorithm. 19 The optimized parameters are summarized in Tables S3−S7. The software-specific parameters that cannot be optimized by Paramounter were determined by consulting with the corresponding software developers of each peak picking algorithm and are summarized in Table S8.…”

“…The raw data were first converted by MSconvert to .mzXML and .mzML formats as required by different kinds of data processing software. Paramounter was used to optimize the data processing parameters for each dataset in each peak picking algorithm . The optimized parameters are summarized in Tables S3–S7.…”

A Dual UHPLC-HRMS-Based Fecal Metabolomics and Lipidomics Analysis and Automated Data Processing Pipeline for Comprehen-sive Gut Phenotyping

“…Two important challenges in untargeted preprocessing of metabolomics data are parameter optimization and the detection of false positive peaks [22][23][24] . The first challenge entails that proprietary and open-source parameter settings for preprocessing are frequently difficult to interpret and suboptimal parameter settings can lead to biased results [25][26][27] . Thus, parameter optimization is required for the different steps in data preprocessing (extraction of ion traces, peak detection, adjusting RTs, grouping peaks into features, …), which all involve different algorithms (e.g.…”

“…cent-Wave 10 and OBI-Warp 28 ). Therefore, to facilitate automatic parameter optimization, several tools have been developed, like e.g., Isotopologue Parameter Optimization (IPO) 26 , Autotuner 25 and Paramounter 27 . The hence-obtained optimized parameters generally outperform default settings but can be topped by expert-chosen parameter settings 29 .…”