Large-scale untargeted LC-MS metabolomics data correction using between-batch feature alignment and cluster-based within-batch signal intensity drift correction

INTRODUCTION: Liquid chromatography-mass spectrometry (LC-MS) is a commonly used technique in untargeted metabolomics owing to broad coverage of metabolites, high sensitivity and simple sample preparation. However, data generated from multiple batches are affected by measurement errors inherent to alterations in signal intensity, drift in mass accuracy and retention times between samples both within and between batches. These measurement errors reduce repeatability and reproducibility and may thus decrease the power to detect biological responses and obscure interpretation. OBJECTIVE: Our aim was to develop procedures to address and correct for within- and between-batch variability in processing multiple-batch untargeted LC-MS metabolomics data to increase their quality. METHODS: Algorithms were developed for: (i) alignment and merging of features that are systematically misaligned between batches, through aggregating feature presence/missingness on batch level and combining similar features orthogonally present between batches; and (ii) within-batch drift correction using a cluster-based approach that allows multiple drift patterns within batch. Furthermore, a heuristic criterion was developed for the feature-wise choice of reference-based or population-based between-batch normalisation. RESULTS: In authentic data, between-batch alignment resulted in picking 15 % more features and deconvoluting 15 % of features previously erroneously aligned. Within-batch correction provided a decrease in median quality control feature coefficient of variation from 20.5 to 15.1 %. Algorithms are open source and available as an R package (‘batchCorr’). CONCLUSIONS: The developed procedures provide unbiased measures of improved data quality, with implications for improved data analysis. Although developed for LC-MS based metabolomics, these methods are generic and can be applied to other data suffering from similar limitations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-016-1124-4) contains supplementary material, which is available to authorized users.