An Efficient Method to Calculate the Aggregated Isotopic Distribution and Exact Center-Masses

In this article, we present a computation- and memory-efficient method to calculate the probabilities of occurrence and exact center-masses of the aggregated isotopic distribution of a molecule. The method uses fundamental mathematical properties of polynomials given by the Newton-Girard theorem and Viete’s formulae. The calculation is based on the atomic composition of the molecule and the natural abundances of the elemental isotopes in normal terrestrial matter. To evaluate the performance of the proposed method, which we named BRAIN, we compare it with the results obtained from five existing software packages (IsoPro, Mercury, Emass, NeutronCluster, and IsoDalton) for 10 biomolecules. Additionally, we compare the computed mass centers with the results obtained by calculating, and subsequently aggregating, the fine isotopic distribution for two of the exemplary biomolecules. The algorithm will be made available as a Bioconductor package in R, and is also available upon request.

[1]  Catherine Fenselau,et al.  Isotopic distributions in mass spectra of large molecules , 1983 .

[2]  A. Rockwood,et al.  Isotopic compositions and accurate masses of single isotopic peaks , 2003, Journal of the American Society for Mass Spectrometry.

[3]  P. D. P. Taylor,et al.  Isotopic Compositions of the Elements 1997 , 1998 .

[4]  Alan L. Rockwood,et al.  Relationship of Fourier transforms to isotope distribution calculations , 1995 .

[5]  J. Yergey.  A GENERAL APPROACH TO CALCULATING ISOTOPIC DISTRIBUTIONS FOR MASS SPECTROMETRY. , 1983, Journal of mass spectrometry : JMS.

[6]  S. Roussis,et al.  Reduction of chemical formulas from the isotopic peak distributions of high-resolution mass spectra. , 2003, Analytical chemistry.

[7]  James A. McCloskey,et al.  Calculations of isotopic distribution in molecules extensively labeled with heavy isotopes , 1977 .

[8]  Tomasz Burzykowski,et al.  The isotopic distribution conundrum. , 2012, Mass spectrometry reviews.

[9]  Klaus Biemann,et al.  Mass spectrometry : organic chemical applications , 1962 .

[10]  Pengyu Hong,et al.  Memory-efficient calculation of the isotopic mass states of a molecule. , 2010, Rapid communications in mass spectrometry : RCM.

[11]  Alan L. Rockwood,et al.  Ultrahigh Resolution Isotope Distribution Calculations , 1996 .

[12]  A. Rockwood,et al.  Ultrahigh-speed calculation of isotope distributions. , 1996, Analytical chemistry.

[13]  A. Rockwood,et al.  Efficient calculation of accurate masses of isotopic peaks , 2006, Journal of the American Society for Mass Spectrometry.

[14]  Jean YH Yang,et al.  Bioconductor: open software development for computational biology and bioinformatics , 2004, Genome Biology.

[15]  D. Stevenson.  Mass Spectrometry and its Applications to Organic Chemistry. , 1961 .

[16]  I. G. MacDonald,et al.  Symmetric functions and Hall polynomials , 1979 .

[17]  Edmond J. Breen,et al.  Automatic Poisson peak harvesting for high throughput protein identification , 2000, Electrophoresis.

[18]  Ross K. Snider.  Efficient calculation of exact mass isotopic distributions , 2007, Journal of the American Society for Mass Spectrometry.

[19]  M. Senko,et al.  Determination of monoisotopic masses and ion populations for large biomolecules from resolved isotopic distributions , 1995, Journal of the American Society for Mass Spectrometry.

[20]  Pengyu Hong,et al.  A hierarchical algorithm for calculating the isotopic fine structures of molecules , 2008, Journal of the American Society for Mass Spectrometry.

[21]  Marilyn L. Brownawell,et al.  A Program for the Synthesis of Mass Spectral Isotopic Abundances. , 1982 .

[22]  D. Hochstrasser,et al.  Modeling peptide mass fingerprinting data using the atomic composition of peptides , 1999, Electrophoresis.

[23]  Tomasz Burzykowski,et al.  Using a Poisson approximation to predict the isotopic distribution of sulphur-containing peptides in a peptide-centric proteomic approach. , 2007, Rapid communications in mass spectrometry : RCM.

[24]  A. Yergey,et al.  Calculation of the isotope cluster for polypeptides by probability grouping , 2009, Journal of the American Society for Mass Spectrometry.

[25]  Tomasz Burzykowski,et al.  A model-based method for the prediction of the isotopic distribution of peptides , 2008, Journal of the American Society for Mass Spectrometry.