SIMILE enables alignment of fragmentation mass spectra with statistical significance

Abstract

Interrelating compounds according to their aligned fragmentation spectra is central to tandem mass spectrometry-based metabolomics. However, current alignment algorithms do not provide statistical significance and compounds that have multiple delocalized structural differences often fail to have their fragment ions aligned. Significant Interrelation of MS/MS Ions via Laplacian Embedding (SIMILE) is a new tool inspired by protein sequence alignment for aligning fragmentation spectra with statistical significance and allowance for multiple chemical differences. We found SIMILE yields 550% more pairs of structurally similar compounds than commonly used cosine-based scoring algorithms, and anticipate SIMILE will fill an important role by also providing p-values for fragmentation spectra alignments to explore structural relationships between compounds.