Testing an alternative search algorithm for compound identification with the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’

Abstract

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Identification of small molecules using accurate mass MS/MS search

“…The Wiley "MSforID" search algorithm is available with the MSforID library and uses a relative average match probability (ramp) score. 105,168 The software calculates the similarity of fragment ions from the unknown MS/MS spectrum versus the library spectra. From the matching fragments a reference spectrum-specific match probability (mp) is then calculated.…”

“…Other “similarity measures” such as the Jaccard, Pearson, Jeffries‐Matusita distance, and random projection can be used as well. A number of modified search algorithms with the aim to improve scoring results have been published . Many of the modified methods introduce correction factors to increase hit scores and sensitivity and specificity of search results.…”

“…can be used as well. A number of modified search algorithms with the aim to improve scoring results have been published [103][104][105]. Many of the modified methods introduce correction factors to increase hit scores MS spectra have sparse product ion peaks, sometimes less than five ions.…”

Metabolomics‐based parallel discovery of xenobiotics and induced endogenous metabolic dysregulation in clinical toxicology

“…In such analysis, both accurate MS and tandem MS data of samples from intoxicated individuals are recorded using either data‐dependent acquisition (Kwok, Choi, Tsoi, Leung, & Wan, ) or data‐independent acquisition (Chindarkar, Wakefield, Stone, & Fitzgerald, ). The identification of xenobiotics in the collected LC–MS datasets is then accomplished by targeted data processing: searching the m/z , isotope pattern, element composition, fragmentation and/or retention time against the chemical standards in a database or an in‐house library (Little, Williams, Pshenichnov, & Tkachenko, ; Oberacher, Whitley, Berger, & Weinmann, ).…”

SANIST: optimization of a technology for compound identification based on the European Union directive with applications in forensic, pharmaceutical and food analyses

“…The larger spectra databases are associated with EI technology (about 40 000) while the CID‐MS/MS database contains fewer candidates (about 9000 compounds). This is mainly due to the fact that the inter‐instrument mass spectra reproducibility is high in EI conditions, while in CID‐MS/MS conditions a strong compound mass spectrum variability is present depending on the instrument employed . However, this probability calculation approach fails in the case of multiple reaction monitoring collision spectra (MRM), where only few specific ion transitions are present in the spectra.…”