Recent advances and prospects of computational methods for metabolite identification: a review with emphasis on machine learning approaches

Motivation: Metabolomics involves studies of a great number of metabolites, which are small molecules present in biological systems. They play a lot of important functions such as energy transport, signaling, building block of cells and inhibition/catalysis. Understanding biochemical characteristics of the metabolites is an essential and significant part of metabolomics to enlarge the knowledge of biological systems. It is also the key to the development of many applications and areas such as biotechnology, biomedicine or pharmaceuticals. However, the identification of the metabolites remains a challenging task in metabolomics with a huge number of potentially interesting but unknown metabolites. The standard method for identifying metabolites is based on the mass spectrometry (MS) preceded by a separation technique. Over many decades, many techniques with different approaches have been proposed for MS-based metabolite identification task, which can be divided into the following four groups: mass spectra database, in silico fragmentation, fragmentation tree and machine learning. In this review paper, we thoroughly survey currently available tools for metabolite identification with the focus on in silico fragmentation, and machine learning-based approaches. We also give an intensive discussion on advanced machine learning methods, which can lead to further improvement on this task.