Quantitative Evaluation of Ion Chromatogram Extraction Algorithms.

Abstract

Extracted ion chromatograms (XIC) are the fundamental signal unit in mass spectrometry. There are many algorithms for analyzing raw mass spectrometry data tasked with distinguishing real isotopic signals from noise. While one or more of the available algorithms are typically chained together for end-to-end mass spectrometry analysis, analysis of each algorithm in isolation provides a specific measurement of the strengths and weaknesses of each approach. Though qualitative opinions on extraction algorithm performance abound, quantitative performance has never been publicly ascertained. Quantitative evaluation has not occurred partly due to the lack of an available quantitative ground truth MS1 data set. Using a recently published, manually extracted XICs as ground truth data, we evaluate the quality of popular XIC algorithms, including MaxQuant, MZMine2, and several methods from XCMS. The manually curated data set comprises 48 human proteins stratified over 6 abundance orders of magnitude. Signals in the sample were manually curated into XIC using a commercial tool for visually identifying XIC and isotopic envelopes. XIC algorithms were applied to the manually extracted data using a grid search of possible parameters. Performance varied greatly between different parameter settings, though nearly all algorithms with parameter settings optimized with respect to the number of true positives recovered over 10 000 XICs.