Compound identification is a critical step in untargeted metabolomics. Its most important procedure is to calculate the similarity between experimental mass spectra and either predicted mass spectra or mass spectra in a mass spectral library. Unlike the continuous similarity measures, there is no study to assess the performance of binary similarity measures in compound identification, even though the well-known Jaccard similarity measure has been widely used without proper evaluation. The objective of this study is thus to evaluate the performance of binary similarity measures for compound identification in untargeted metabolomics. Fifteen binary similarity measures, including the well-known Jaccard, Dice, Sokal-Sneath, Cosine, and Simpson measures, were selected to assess their performance in compound identification. using both electron ionization (EI) and electrospray ionization (ESI) mass spectra. Our theoretical evaluations show that the accuracy of the compound identification was exactly the same between the Jaccard, Dice, 3W-Jaccard, Sokal-Sneath, and Kulczynski measures, between the Cosine and Hellinger measures, and between the McConnaughey and Driver-Kroeber measures, which were practically confirmed using mass spectra libraries. From the mass spectrum-based evaluation, we observed that the best performing similarity measures were the McConnaughey and Driver-Kroeber measures for EI mass spectra and the Cosine and Hellinger measures for ESI mass spectra. The most robust similarity measure was the Fager-McGowan measure, the second-best performing similarity measure in both EI and ESI mass spectra.
Keywords: EI; ESI; binary similarity measure; compound identification; mass spectrometry; untargeted metabolomics.