Quantitative Evaluation of Algorithms for Isotopic Envelope Extraction via Extracted Ion Chromatogram Clustering

LC-MS precursor (MS1) data are used increasingly often in conjunction with MS/MS data for the quantification, validation, and other computational mass spectrometry tasks. The efficacy of MS1 data on downstream tasks is dependent on the coverage and accuracy of the MS1 isotopic envelope extraction algorithms that delineate them from the dense backgrounds common in complex samples. Although several algorithms for extracted ion chromatogram (XIC) clustering exist, their performance has not yet been quantified, in part due to the difficulty of obtaining, isolating, and running some algorithms and in part due to the lack of quantitative MS1 ground truth. Using a newly available manually annotated ground truth data set, we measure the performance of several popular XIC clustering algorithms in time, coverage, and accuracy of resulting isotopic envelopes. We intend this work to provide a benchmark against which future algorithms can be scored.