On the inter‐instrument and the inter‐laboratory transferability of a tandem mass spectral reference library: 2. Optimization and characterization of the search algorithm

Abstract

A sophisticated matching algorithm developed for highly efficient identity search within tandem mass spectral libraries is presented. For the optimization of the search procedure a collection of 410 tandem mass spectra corresponding to 22 compounds was used. The spectra were acquired in three different laboratories on four different instruments. The following types of tandem mass spectrometric instruments were used: quadrupole-quadrupole-time-of-flight (QqTOF), quadrupole-quadrupole-linear ion trap (QqLIT), quadrupole-quadrupole-quadrupole (QqQ), and linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer (LIT-FTICR). The obtained spectra were matched to an established MS/MS-spectral library that contained 3759 MS/MS-spectra corresponding to 402 different reference compounds. All 22 test compounds were part of the library. A dynamic intensity cut-off, the search for neutral losses, and optimization of the formula used to calculate the match probability were shown to significantly enhance the performance of the presented library search approach. With the aid of these features the average number of correct assignments was increased to 98%. For statistical evaluation of the match reliability the set of fragment ion spectra was extended with 300 spectra corresponding to 100 compounds not included in the reference library. Performance was checked with the aid of receiver operating characteristic (ROC) curves. Using the magnitude of the match probability as well as the precursor ion mass as benchmarks to rate the obtained top hit, overall correct classification of a compound being included or not included in the mass spectrometric library, was obtained in more than 95% of cases clearly indicating a high predictive accuracy of the established matching procedure.

Analytical Validation of a Portable Mass Spectrometer Featuring Interchangeable, Ambient Ionization Sources for High Throughput Forensic Evidence Screening

“…Pertinent MS/MS spectral information (i.e., precursor ion m/z, fragment ion(s) m/z, relative ion intensities) was submitted for compound identification with the MSforID library search program [58,59]. The search algorithm determines the degree of similarity between a sample spectrum and library spectra, expressed as a 'relative average match probability' (ramp).…”

Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review

“…Oberacher et al designed a multicenter study in which 22 test compounds (drug standards) were sent to three different laboratories, where 418 tandem mass spectra were acquired using four different instruments from two manufacturers including Q-TOF, triple quadrupole, Q-Trap and FTICR mass spectrometers [126]. CID mass spectra were recorded without any standardization of experimental conditions and they were matched against a reference library using a sophisticated matching algorithm [127]. …”

Mass Spectrometry

“…For instance, a newly presented ''matching probability'' (mp) uses a high weight for the presence and absence of peaks (raised to the fourth power!) and a low weight for the intensity differences [64]: Another algorithm, X-Rank [65], ranks the peaks of the mass spectra by intensity and matches the rank pattern of the reference spectrum with the rank pattern of the unknown. The probability of a correct identification is computed for this match using parameters that have been trained before.…”