Abstract
Untargeted metabolomics seeks to identify and quantify most metabolites in a biological system. In general, metabolomics results are represented by numerical matrices containing data that represent the intensities of the detected variables. These matrices are subsequently analyzed by methods that seek to extract significant biological information from the data. In mass spectrometry-based metabolomics, if mass is detected with sufficient accuracy, below 1 ppm, it is possible to derive mass-difference networks, which have spectral features as nodes and chemical changes as edges. These networks have previously been used as means to assist formula annotation and to rank the importance of chemical transformations. In this work, we propose a novel role for such networks in untargeted metabolomics data analysis: we demonstrate that their properties as graphs can also be used as signatures for metabolic profiling and class discrimination. For several benchmark examples, we computed six graph properties and we found that the degree profile was consistently the property that allowed for the best performance of several clustering and classification methods, reaching levels that are competitive with the performance using intensity data matrices and traditional pretreatment procedures. Furthermore, we propose two new metrics for the ranking of chemical transformations derived from network properties, which can be applied to sample comparison or clustering. These metrics illustrate how the graph properties of mass-difference networks can highlight the aspects of the information contained in data that are complementary to the information extracted from intensity-based data analysis.