Algorithms for automatic interpretation of high resolution mass spectra

Abstract

Automated interpretation of high-resolution mass spectra in a reliable and efficient manner represents a highly challenging computational problem. This work aims at developing methods for reducing a high-resolution mass spectrum into its monoisotopic peak list, and automatically assigning observed masses to known fragment ion masses if the protein sequence is available. The methods are compiled into a suite of data reduction algorithms which is called MasSPIKE (Mass Spectrum Interpretation and Kernel Extraction). MasSPIKE includes modules for modeling noise across the spectrum, isotopic cluster identification, charge state determination, separation of overlapping isotopic distributions, picking isotopic peaks, aligning experimental and theoretical isotopic distributions for estimating a monoisotopic peak's location, generating the monoisotopic mass list, and assigning the observed monoisotopic masses to possible protein fragments. The method is tested against a complex top-down spectrum of bovine carbonic anhydrase. Results of each of the individual modules are compared with previously published work. (J Am Soc Mass Spectrom 2006, 17, 459 -468)

Phase Correction of Fourier Transform Ion Cyclotron Resonance Mass Spectra Using MatLab

“…While not currently tested, it seems likely that improvements can be made to the peak centroiding algorithm, which will improve the accuracy of the Φ/ω pairs that are added to the least squares fit. Possible ways of improving centroiding algorithms include the use of a maximum likelihood peakfitting method [45], a center-of-mass calculation, a least-squares fit to a Lorentzian (or Lorentzian/sinc) function, apodization and fitting to a Gaussian function, or even use of the shifted-basis method [46]. In this work, none of …”

Extensive Charge Reduction and Dissociation of Intact Protein Complexes Following Electron Transfer on a Quadrupole-Ion Mobility-Time-of-Flight MS

“…However, because of the presence of potentially overlapping charge states and significant peak widths, charge state assignment can still be challenging, particularly for polydisperse samples or in complex mixtures. As a result, a number of specialized algorithms have been proposed to deconvolute these spectra and identify the components [6][7][8][9][10][11][12]. Another approach is to minimize mass spectral complexity by reducing the charge state of the ions in the gas phase by means of Bcharge-stripping^ [13][14][15][16][17].…”

Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins

“…The spectra were analyzed by an in-house program called°MasSpike° [62],°similar°to°Thrash° [63],°which reduces each spectrum into the monoisotopic peak list of the fragment ions. This program operates by identifying isotopic clusters based on S/N ratio.…”