title: A batch correction method for liquid chromatography-mass spectrometry data that does not depend on quality control samples.
abstract: The need for reproducible and comparable results is of increasing importance in non-targeted metabolomic studies, especially when differences between experimental groups are small. Liquid chromatography-mass spectrometry spectra are often acquired batch-wise so that necessary calibrations and cleaning of the instrument can take place. However this may introduce further sources of variation, such as differences in the conditions under which the acquisition of individual batches is performed. Quality control (QC) samples are frequently employed as a means of both judging and correcting this variation. Here we show that the use of QC samples can lead to problems. The non-linearity of the response can result in substantial differences between the recorded intensities of the QCs and experimental samples, making the required adjustment difficult to predict. Furthermore, changes in the response profile between one QC interspersion and the next cannot be accounted for and QC based correction can actually exacerbate the problems by introducing artificial differences. "Background correction" methods utilise all experimental samples to estimate the variation over time rather than relying on the QC samples alone. We compare non-QC correction methods with standard QC correction and demonstrate their success in reducing differences between replicate samples and their potential to highlight differences between experimental groups previously hidden by instrumental variation.
authors.affiliation: York Centre for Complex Systems Analysis, University of York, YO10 5GE, York UK ; Department of Computer Science, University of York, York, YO10 5DD UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Rusilowicz
authors.affiliation: Fera Science Ltd, York, YO41 1LZ UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Dickinson
authors.affiliation: Fera Science Ltd, York, YO41 1LZ UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Charlton
authors.affiliation: York Centre for Complex Systems Analysis, University of York, YO10 5GE, York UK ; Department of Computer Science, University of York, York, YO10 5DD UK.
authors.forename: Simon
authors.initials: S
authors.lastname: O'Keefe
authors.affiliation: York Centre for Complex Systems Analysis, University of York, YO10 5GE, York UK ; Departments of Mathematics and Chemistry, University of York, York, YO10 5DD UK.
authors.forename: Julie
authors.identifier: 0000-0002-5171-8480
authors.initials: J
authors.lastname: Wilson
keywords: Batch correction; LC–MS; Mass spectrometry; Metabolomics; QC correction; Quality control