AdductHunter: identifying protein-metal complex adducts in mass spectra

Abstract

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.

Keywords: Constraint integer optimization; Dynamic time warping; Mass spectrometry; Protein adducts.

Fig. 1

Webpage layout showing input files and parameters for peak identification and the constraint optimization formulation

Fig. 2

Overview of the underlying algorithm to AdductHunter

Fig. 3

Peaks identified in mass spectra recorded for ubiquitin (Ub) and cisplatin mixtures at low, medium, and high resolution

Fig. 4

Missing (top) and false positive (bottom) proportion of peaks at different minimum peak heights for increasing tolerance values

Fig. 5

Missing proportion of species which improves as the tolerance is increased, albeit with diminishing returns in accuracy