Informed baseline subtraction of proteomic mass spectrometry data aided by a novel sliding window algorithm

Abstract

Proteomic matrix-assisted laser desorption/ionisation (MALDI) linear time-of-flight (TOF) mass spectrometry (MS) may be used to produce protein profiles from biological samples with the aim of discovering biomarkers for disease. However, the raw protein profiles suffer from several sources of bias or systematic variation which need to be removed via pre-processing before meaningful downstream analysis of the data can be undertaken. Baseline subtraction, an early pre-processing step that removes the non-peptide signal from the spectra, is complicated by the following: (i) each spectrum has, on average, wider peaks for peptides with higher mass-to-charge ratios (m/z), and (ii) the time-consuming and error-prone trial-and-error process for optimising the baseline subtraction input arguments. With reference to the aforementioned complications, we present an automated pipeline that includes (i) a novel `continuous' line segment algorithm that efficiently operates over data with a transformed m/z-axis to remove the relationship between peptide mass and peak width, and (ii) an input-free algorithm to estimate peak widths on the transformed m/z scale. The automated baseline subtraction method was deployed on six publicly available proteomic MS datasets using six different m/z-axis transformations. Optimality of the automated baseline subtraction pipeline was assessed quantitatively using the mean absolute scaled error (MASE) when compared to a gold-standard baseline subtracted signal. Near-optimal baseline subtraction was achieved using the automated pipeline. The advantages of the proposed pipeline include informed and data specific input arguments for baseline subtraction methods, the avoidance of time-intensive and subjective piecewise baseline subtraction, and the ability to automate baseline subtraction completely. Moreover, individual steps can be adopted as stand-alone routines.Comment: 50 pages, 19 figure