Linear MALDI-ToF simultaneous spectrum deconvolution and baseline removal

Abstract

BackgroundThanks to a reasonable cost and simple sample preparation procedure, linear MALDI-ToF spectrometry is a growing technology for clinical microbiology. With appropriate spectrum databases, this technology can be used for early identification of pathogens in body fluids. However, due to the low resolution of linear MALDI-ToF instruments, robust and accurate peak picking remains a challenging task. In this context we propose a new peak extraction algorithm from raw spectrum. With this method the spectrum baseline and spectrum peaks are processed jointly. The approach relies on an additive model constituted by a smooth baseline part plus a sparse peak list convolved with a known peak shape. The model is then fitted under a Gaussian noise model. The proposed method is well suited to process low resolution spectra with important baseline and unresolved peaks.ResultsWe developed a new peak deconvolution procedure. The paper describes the method derivation and discusses some of its interpretations. The algorithm is then described in a pseudo-code form where the required optimization procedure is detailed. For synthetic data the method is compared to a more conventional approach. The new method reduces artifacts caused by the usual two-steps procedure, baseline removal then peak extraction. Finally some results on real linear MALDI-ToF spectra are provided.ConclusionsWe introduced a new method for peak picking, where peak deconvolution and baseline computation are performed jointly. On simulated data we showed that this global approach performs better than a classical one where baseline and peaks are processed sequentially. A dedicated experiment has been conducted on real spectra. In this study a collection of spectra of spiked proteins were acquired and then analyzed. Better performances of the proposed method, in term of accuracy and reproductibility, have been observed and validated by an extended statistical analysis.

Semi-Quantitative MALDI Measurements of Blood-Based Samples for Molecular Diagnostics

“…To improve upon the accuracy of our peak detection algorithm, particularly for overlapping peaks, we utilize a convolution approach whereby the spectrum is convoluted with the peak shape function of the instrument. Previous work has successfully used Gaussian functions to describe the peak shape of MALDI-TOF mass spectra [28,30], but we find this simpler approach insufficient, especially at higher masses. Individual peaks that we have observed in typical spectra are asymmetrically broadened, with the right side (high-mass side) being wider than the left side (low-mass side).…”

“…They often rely on simply finding candidate peaks, either through local intensity maxima or by finding minima in the second derivatives of the intensity, and then using intensity thresholding to select real peaks from the selection of candidate peaks. Although this method is computationally fast, it can fail to detect peaks when they overlap and may struggle to work well when there are large changes in peak intensity [27,28]. Improved peak detection algorithms using a continuous wavelet transform exhibit improved peak detection, but they often may not be accurate in the case of overlapping peaks or highly asymmetric peaks [25,26].…”

Fast visual exploration of mass spectrometry images with interactive dynamic spectral similarity pseudocoloring

“…This has the advantage to be highly efficient, which is especially important for the interactive variant, as it requires a fast visual response. If necessary, the peak detection could also be extended with more complex methods 24 – 27 .…”

High‐resolution mass spectrometry (HRMS): Focus on the m/z values estimated by the Savitzky–Golay first derivative

“…The Savitzky–Golay (SG) algorithm 1 has been proposed in mass spectrometry for noise removal and smoothing, 2–8 for baseline correction, 5 for peak picking, 9,10 and more recently for the improvement of m/z values by Picaud et al 11 We investigated this idea further. Peak picking was obtained by a home‐made calculation, beyond the scope of this paper.…”