Investigating Time Series Classification Techniques for Rapid Pathogen Identification with Single-Cell MALDI-TOF Mass Spectrum Data

Abstract

Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) is a well-known technology, widely used in species identification. Specifically, MALDI-TOF-MS is applied on samples that usually include bacterial cells, generating representative signals for the various bacterial species. However, for a reliable identification result, a significant amount of biomass is required. For most samples used for diagnostics of infectious diseases, the sample volume is extremely low to obtain the required amount of biomass. Therefore, amplification of the bacterial load is performed by a culturing phase. If the MALDI process could be applied to individual bacteria, it would be possible to circumvent the need for culturing and isolation, accelerating the whole process. In this paper, we briefly describe an implementation of a MALDI-TOF MS procedure in a setting of individual cells and we demonstrate the use of the produced data for the application of pathogen identification. The identification of pathogens (bacterial species) is performed by using machine learning algorithms on the generated single-cell signals. The high predictive performance of the machine learning models indicates that the produced bacterial signatures constitute an informative representation, helpful in distinguishing the different bacterial species. In addition, we reformulate the bacterial species identification problem as a time series classification task by considering the intensity sequences of a given spectrum as time series values. Experimental results show that algorithms originally introduced for time series analysis are beneficial in modelling observations of single-cell MALDI-TOF MS.