IsoSpec: Hyperfast Fine Structure Calculator.

As high-resolution mass spectrometry (HRMS) becomes increasingly available, the need of software tools capable of handling more complex data is surging. The complexity of the HRMS data stems partly from the presence of isotopes that give rise to more peaks to interpret compared to lower resolution instruments. However, a new generation of fine isotope calculators is on the rise. They calculate the smallest possible sets of isotopologues. However, none of these calculators lets the user specify the joint probability of the revealed envelope in advance. Instead, the user must provide a lower limit on the probability of isotopologues of interest, that is, provide minimal peak height. The choice of such threshold is far from obvious. In particular, it is impossible to a priori balance the trade-off between the algorithm speed and the portion of the revealed theoretical spectrum. We show that this leads to considerable inefficiencies. Here, we present IsoSpec: an algorithm for fast computation of isotopologues of chemical substances that can alternate between joint probability and peak height threshold. We prove that IsoSpec is optimal in terms of time complexity. Its implementation is freely available under a 2-clause BSD license, with bindings for C++, C, R, and Python.

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

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

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

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

[5]  A. Gambin,et al.  BRAIN: a universal tool for high-throughput calculations of the isotopic distribution for mass spectrometry. , 2013, Analytical chemistry.

[6]  Andreas Ipsen.  Efficient calculation of exact fine structure isotope patterns via the multidimensional Fourier transform. , 2014, Analytical chemistry.

[7]  Zsuzsanna Lipták,et al.  SIRIUS: decomposing isotope patterns for metabolite identification , 2008, Bioinform..

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

[9]  H. M. Finucan.  The mode of a multinomial distribution , 1964 .

[10]  M. Talagrand.  A new look at independence , 1996 .

[11]  M. Mann,et al.  Ultra High Resolution Linear Ion Trap Orbitrap Mass Spectrometer (Orbitrap Elite) Facilitates Top Down LC MS/MS and Versatile Peptide Fragmentation Modes* , 2011, Molecular & Cellular Proteomics.

[12]  Chad R Weisbrod,et al.  21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: A National Resource for Ultrahigh Resolution Mass Analysis , 2015, Journal of The American Society for Mass Spectrometry.

[13]  Katsutoshi Takahashi,et al.  Power of isotopic fine structure for unambiguous determination of metabolite elemental compositions: in silico evaluation and metabolomic application. , 2014, Analytica chimica acta.

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

[15]  Francesco Corona,et al.  Accelerated isotope fine structure calculation using pruned transition trees. , 2015, Analytical chemistry.

[16]  Feng Xian,et al.  Mass resolution and mass accuracy: how much is enough? , 2013, Mass spectrometry.

[17]  Stefan R Bornstein,et al.  Shotgun lipidomics on high resolution mass spectrometers. , 2011, Cold Spring Harbor perspectives in biology.

[18]  A. Rockwood,et al.  On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry , 2015, Journal of The American Society for Mass Spectrometry.

[19]  W. Brand,et al.  Assessment of international reference materials for isotope-ratio analysis (IUPAC Technical Report) , 2014 .

[20]  E. Nikolaev,et al.  Fine structure in isotopic peak distributions measured using a dynamically harmonized Fourier transform ion cyclotron resonance cell at 7 T. , 2012, Analytical chemistry.