MS-Pep: a computer program for the interpretation of mass spectra of peptide libraries

Electrospray mass spectrometry (ESI-MS) is an established method for the qualitative analysis of synthetic peptide libraries and combinatorial mixtures or collections of small organic compounds. However, the calculation of the mass distribution of even small peptide mixtures is a time-consuming and error-proned task. Therefore, the computer program MS-Pep has been developed, which calculates the masses of expected peptides, byproducts and the mass distributions of peptide libraries. Received: 2 December 1996 / Revised: 17 April 1997 / Accepted: 21 April 1997     

Computer-aided interpretation of mass spectra

A system is described in which computer techniques are used to carry out major steps in the procedure for interpretation of high-resolution mass spectral data. These steps include identification and evaluation of the molecular ion, neutral fragments lost from the molecular ion, and characteristic ion series, followed by elucidation of specific structural details using a sub-routine for the particular compound class selected. The technique shows promise of not only increasing the interpreter's efficiency, but of providing more specific and detailed structural information from the spectral data.     

RScore: a peptide randomicity score for evaluating tandem mass spectra

RScore, a new criterion of randomicity for evaluating tandem mass (MS/MS) spectra, is described. RScore is defined as the relative quality in cross-correlation and matched intensity percentage of a potentially positive peptide to those of other possible candidates for the same spectrum. By utilizing RScore combined with less stringent SEQUEST score filters, the number of true positive peptides can be increased and the number of false positives in datasets from a known protein mixture can be reduced compared with current SEQUEST parameters used alone. This algorithm is simple and adds little overheads to SEQUEST computation.     

Computer programmes for representing mass spectra on a computer plotter

The Fortran IV programmes have been written for plotting mass spectra on a Calcomp 565 plotter. The spectra can be displayed sequentially or one on top of the other. One of the programmes also calculates relative abundance and percent sigma for each peak, and possible origins for metastable peaks.     

Raman spectra of ionic liquids: interpretation via computer simulation

Theoretical Raman spectra of the complex-forming ionic liquids LaCl3 and ScCl3, derived from molecular dynamics computer simulations, are presented. These simulations, which use polarizable ion interaction models, have previously been shown to predict structural properties in excellent agreement with diffraction experiments. The dependence of the polarizability of the melt on the ionic positions, which determines the Raman spectrum through the time dependence of the polarizability correlation function, is modeled on the basis of ab initio electronic structure calculations carried out on alkali chlorides. New simulation techniques are introduced in order to allow the spectrum to be calculated with acceptable statistics. The calculated spectra are in semiquantitative agreement with experimental data. The distinctive bands which appear in the spectra of such complex melts are linked to the vibrations of the transient coordination complexes which form in these melts and new interpretations for the origin of several well-known features are proposed. The simulations thus enable a link between the structure of a melt as perceived through Raman spectroscopy and through diffraction experiments to be made.     

Multidimensional computer evaluation of mass spectra

The increasing importance of spectroscopic methods as an analytical tool in industry, combined with the trend to automatize spectrometers, demands new standards in the quantity and quality of spectrum interpretation. Suitable computer programs should be able to predict structural features from mass spectral properties. The knowledge base is a structure-oriented mass spectral data collection consisting of some 42000 spectra and topologies. The comparison of selected mass spectral properties such as similarity, neutral losses and ion series of the unknown with the equivalent properties of the library spectra results in a set of corresponding structures. Subsequent substructure analysis yields a histogram of substructure frequencies containing information about their statistical relevance. The relevant substructure set may be recombined to produce a structure proposal, as is demonstrated for 1-acetyl-2-methoxy-4-trimethylsilyioxybenzene. In a second example, the relevant substructures derived by the interpretation system are used as input for the ¹³C-NMR substructure generator. This procedure reduces the solution space of the structure prediction algorithm considerably. Besides the spectrum interpretation, additional possibilities are available. The substructure search enables us, for example, to look for mass spectrometric reaction centres. Beyond that, substructure analysis is applicable to the determination of structural features typical of certain combinations of neutral losses and/or characteristic fragments.     

Algorithms for automatic interpretation of high resolution mass spectra

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.     

A simple computer program for high resolution gamma-ray spectra

A computer program is presented, which locates peaks in high-resolution γ-ray spectra and determines their content. The program has been written in Basic; ‘translations’ have been made into Fortran and Algol. For detailed information the reader is referred to the original TNO Report CL 69/137.     

PeakSelect: preprocessing tandem mass spectra for better peptide identification

We present a new preprocessing method, PeakSelect, to improve the accuracy and efficiency of Tandem Mass-Spec peptide (protein) identification. The fundamental difference between noise and fragment ions in spectra is that ions have isotopes but noise does not. We propose a new and important concept of an Isotope Pattern Vector (IPV) which characterizes the isotope cluster of fragment ions. Then the noise and real peaks can be distinguished by the quantitative IPV values. PeakSelect first uses a new method of the Gaussian Mixture Model and Expectation-Maximization (EM) algorithm to find the base intensity level (baseline) in a spectrum. Then PeakSelect selects features based on the IPV and baseline, and constructs a decision tree to automatically classify the peaks into different categories such as noise, single ion peaks, and overlapping peaks. Experiments show that PeakSelect can help to reduce the Mascot searching time and increase the reliability of peptide identifications. In particular, PeakSelect performs well on complex spectra with a large number of peaks from large peptides, and supports more sequence identification than other well-known systems.     

The computer-assisted interpretation of copolymer mass spectra

A computer program called MSCOPOL has been developed to aid in the interpretation of copolymer mass spectra. The program reads the mass spectrum, calculates the most likely monomer masses via correlation or Fourier transform methods, determines possible end group masses based on the monomer masses, and can then search monomer and end group data bases for likely chemical moieties. Refinement of the end group result is possible by calculation of the monomer ratio and degree of polymerization as a function of end group mass. The program is written in Microsoft Visual Basic and runs on an IBM compatible PC. Applications are shown for polystyrene, poly(N-vinyl pyrrolidone/vinyl acetate), and poly(ethylene oxide/propylene oxide).     

Software algorithm for automatic interpretation of mass spectra of glycerolipids

A new software algorithm for automatic interpretation of mass spectra of glycerolipids has been developed. The algorithm utilizes a user-specified list of parameters needed to process the spectra. The compounds in mass spectra are identified according to range of measured m/z values, after which the spectra are automatically corrected by the content of naturally occurring isotopes and ion intensities of identified compounds by response correction factors. Automatic processing of the spectra was shown to be accurate and reliable by testing with numerous spectra of glycerophospholipids obtained by liquid chromatography/electrospray ionization mass spectrometry and by comparing the results with manual interpretation of the spectra. If quantitative analysis using internal standards is performed, all the identified compounds in the sample are quantified automatically. A dilution factor may be defined for each sample and is applied to correct the alterations in sample concentration during sample preparation. Processing of several replicate spectra simultaneously produces mean results with standard deviations. The software may also be used to subtract the results of two analyses and to calculate the mean result of replicate subtractions. The algorithm was shown to save time and labor in repetitive processing of mass spectra of similar type. It may be applied to processing of spectra obtained by various mass spectrometric methods.     

A computer system for measuring fast-scan lowresolution mass spectra

A microprocessor-based satellite computer system (MASDAT) controls a low-resolution, fast-scan mass spectrometer for the measurement of series of spectra. Special digitization hardware (logarithmic A/D converter) and software algorithms are necessary to achieve a dynamic range (ratio of highest to lowest intensity) of about 10⁵ in peak heights. Up to three MASDAT satellites can be connected to a host computer. Synchronized parallel programs in the host system communicate with the operator, calibrate the mass scale, print an interscan report, and store final spectra and, optionally, unreduced data on mass storage devices. Host software is described for a RSX11M and for a VAX/VMS operating system.     

PLUMS: a program for the rapid optimization of focused libraries

PLUMS is a new method to perform rational monomer selection for combinatorial chemistry libraries. The algorithm has been developed to optimize focused libraries with specific two-dimensional and/or three-dimensional properties. A preliminary step is the identification of those molecules in the initial virtual library which satisfy the imposed property constraints; we define these molecules as the virtual hits. From the virtual hits, PLUMS generates a starting library, which is the true combinatorial library that includes all the virtual hits. Monomers are then removed in an iterative fashion, thus reducing the size of the library. At each iteration, the worst monomer is removed. Each sublibrary is selected using a global scoring function, which balances effectiveness and efficiency. The iterative process continues until one is left with a library that consists entirely of virtual hits. The optimal library, which is the best compromise between effectiveness and efficiency, can then be selected according to the score. During the iterative process, equivalent solutions may well occur and are taken into account by the algorithm, according to a user-defined parameter. The number of monomers for each substitution site and the size of the library are parameters that can be either optimized or used to constrain the selection. The results obtained on two test libraries are presented. PLUMS was compared with genetic algorithms (GA) and monomer frequency analysis (MFA), which are widely used for monomer selection. For the two test libraries, PLUMS and GA gave equivalent results. MFA is the fastest method, but it can give misleading solutions. Possible advantages and disadvantages of the different methods are discussed.     

COMPLX: a computer algorithm for the detection of protein-ligand and other macromolecular complexes in mass spectra

A new algorithm has been designed and tested to identify protein, or any other macromolecular, complexes that have been widely reported in mass spectral data. The program takes advantage of the appearance of multiply charged ions that are common to both electrospray ionization and, to a lesser extent, matrix-assisted laser desorption/ionization (MALDI) mass spectra. The algorithm, known as COMPLX for the COMposition of Protein-Ligand compleXes, is capable of identifying complexes for any protein or macromolecule with a binding partner of molecular mass up to 100 000 Da. It does so by identifying ion pairs present in a mass spectrum that, when they share a common charge, have an m/z value difference that is an integer fraction of a ligand or binding partner molecular mass. Several additional criteria must be met in order for the result to be ranked in the output file including that all m/z values for ions of the protein or complex have progressively lower values as their assigned charge increases, the difference between the m/z values for adjacent charge states (z, z + 1) decrease as the assigned charge state increases, and the ratio of any two m/z values assigned to a protein or complex is equal to the inverse ratio of their charge. The entries that satisfy these criteria are then ranked according to the appearance of ions in the mass spectrum associated with the binding partner, the length of a continuous series of charges across any set of ions for a protein and complex and the lowest error recorded for the molecular mass of the ligand or binding partner. A diverse range of hypothetical and experimental mass spectral data were used to implement and test the program, including those recorded for antibody-peptide, protein-peptide and protein-heme complexes. Spectra of increasing complexity, in terms of the number of ions input, were also successfully analysed in which the number of input m/z values far exceeds the few associated with a macromolecular complex. Thus the program will be of value in a future goal of proteomics, where mass spectrometry already plays a central role, for the direct analysis of protein and other associations within biological extracts.     

A computer program for the collection,reduction and analysis of echelle spectra

This article is an electronic publication in Spectrochimica Acta Electronica (SAE), the electronic section of Spectrochimica Acta Part B (SAB). The hardcopy text, comprising the main article and an appendix, is accompanied by a disk containing the compiled program, a manual, the source code and tutorial in ASCII format, and data files. The work presented is a result of the need to facilitate collection, calibration, and extraction of data from an echelle spectrometer employing charge coupled array detection (CCD). A computer program, written using Microsoft's BASIC Professional Development System version 7.1 under MS DOS, is explained and demonstrated. Wavelength calibration requires critical spectrometer dimensions, grating counter settings, and the identification of a single spectral line. Calibration accuracies are better than ± 1 pixel across a 576 × 384 pixel array. Extraction of intensity-normalized spectra for all detected orders requires less than 3 min on a 33 MHz 80386 personal computer with an 80387 math coprocessor.     

New algorithm for the identification of mass spectra by the computer library search

A library search algorithm for the identification of mass spectra is described. The algorithm creates the mass vector of an unknown compound spectrum and sequentially compares it with the library files vector. A measure indicating similarity of compares vectors - similarity index is calculated on the basis of weighted factors of identical elements of both vectors. A diagnosticity of vectors element defined as a function of mass distribution of library file is taken as an important parameter in similarity index calculation.     

The computer processing and interpretation of mass spectral information. I—The reduction of raw mass spectra to monoisotopic form

An algorithm of the AELITA program (Atomic-Element Identification) is described which enables both low and high resulution mass spectra to be processed to give the elemental composition and ion abundances of the mass spectra in monoisotopic form. The program has no limitations in respect of the elemental composition and spectrum complexity. The criterion for the choice of the most probable solution is based either on the accuracy of measurement of the peak abundances and/or the masses. The program is written in ALGOL, run on a BESM-6 computer, and occupies about 19K core memory.