Multispectrum ModiFinder Site Localization Performance.

Tandem mass spectrometry (MS/MS) is a powerful technique for structural identification of small molecules, yet a significant portion of MS/MS spectra from untargeted experiments remain unidentifiable through spectrum library matching. ModiFinder, a computational tool, tackles this issue by predicting the site of chemical modifications on known analogs of the unidentified compounds using MS/MS data. However, ModiFinder's performance is limited by insufficient peak data and fragmentation annotation ambiguities. In this study, we investigate how incorporating MS/MS spectra from multiple collision energies and mass spectrometry adducts can enhance ModiFinder's localization accuracy. Using a data set from Agilent Technologies comprising 2150 data-rich compounds (five times larger than previously available data sets), we evaluated the impact of complementary spectral information. Our results show that combining spectra from different adducts and collision energies expands ModiFinder's localization abilities to more compounds and improves the overall performance.