MOTIVATION: Identification of small molecules in a biological sample remains a major bottleneck in molecular biology, despite a decade of rapid development of computational approaches for predicting molecular structures using mass spectrometry (MS) data. Recently, there has been increasing interest in utilizing other information sources, such as liquid chromatography (LC) retention time (RT), to improve identifications solely based on MS information, such as precursor mass-per-charge and tandem mass spectrometry (MS2). RESULTS: We put forward a probabilistic modelling framework to integrate MS and RT data of multiple features in an LC-MS experiment. We model the MS measurements and all pairwise retention order information as a Markov random field and use efficient approximate inference for scoring and ranking potential molecular structures. Our experiments show improved identification accuracy by combining MS2 data and retention orders using our approach, thereby outperforming state-of-the-art methods. Furthermore, we demonstrate the benefit of our model when only a subset of LC-MS features has MS2 measurements available besides MS1. AVAILABILITY AND IMPLEMENTATION: Software and data are freely available at https://github.com/aalto-ics-kepaco/msms_rt_score_integration. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Liquid Chromatography (LC) followed by tandem Mass Spectrometry (MS/MS) is one of the predominant methods for metabolite identification. In recent years, machine learning has started to transform the analysis of tandem mass spectra and the identification of small molecules. In contrast, LC data is rarely used to improve metabolite identification, despite numerous published methods for retention time prediction using machine learning. Results: We present a machine learning method for predicting the retention order of molecules; that is, the order in which molecules elute from the LC column. Our method has important advantages over previous approaches: We show that retention order is much better conserved between instruments than retention time. To this end, our method can be trained using retention time measurements from different LC systems and configurations without tedious pre-processing, significantly increasing the amount of available training data. Our experiments demonstrate that retention order prediction is an effective way to learn retention behaviour of molecules from heterogeneous retention time data. Finally, we demonstrate how retention order prediction and MS/MS-based scores can be combined for more accurate metabolite identifications when analyzing a complete LC-MS/MS run. Availability and implementation: Implementation of the method is available at https://version.aalto.fi/gitlab/bache1/retention_order_prediction.git.

In this paper, we present a novel method for solving structured prediction problems, based on combining Input Output Kernel Regression (IOKR) with an extension of magnitude-preserving ranking to structured output spaces. In particular, we concentrate on the case where a set of candidate outputs has been given, and the associated pre-image problem calls for ranking the set of candidate outputs. Our method, called magnitude-preserving IOKR, both aims to produce a good approximation of the output feature vectors, and to preserve the magnitude differences of the output features in the candidate sets. For the case where the candidate set does not contain corresponding ’correct’ inputs, we propose a method for approximating the inputs through application of IOKR in the reverse direction. We apply our method to two learning problems: cross-lingual document retrieval and metabolite identification. Experiments show that the proposed approach improves performance over IOKR, and in the latter application obtains the current state-of-the-art accuracy.