IntroductionBatch effects in large untargeted metabolomics experiments are almost unavoidable, especially when sensitive detection techniques like mass spectrometry (MS) are employed. In order to obtain peak intensities that are comparable across all batches, corrections need to be performed. Since non-detects, i.e., signals with an intensity too low to be detected with certainty, are common in metabolomics studies, the batch correction methods need to take these into account. ObjectivesThis paper aims to compare several batch correction methods, and investigates the effect of different strategies for handling non-detects.MethodsBatch correction methods usually consist of regression models, possibly also accounting for trends within batches. To fit these models quality control samples (QCs), injected at regular intervals, can be used. Also study samples can be used, provided that the injection order is properly randomized. Normalization methods, not using information on batch labels or injection order, can correct for batch effects as well. Introducing two easy-to-use quality criteria, we assess the merits of these batch correction strategies using three large LC–MS and GC–MS data sets of samples from Arabidopsis thaliana.ResultsThe three data sets have very different characteristics, leading to clearly distinct behaviour of the batch correction strategies studied. Explicit inclusion of information on batch and injection order in general leads to very good corrections; when enough QCs are available, also general normalization approaches perform well. Several approaches are shown to be able to handle non-detects—replacing them with very small numbers such as zero seems the worst of the approaches considered.ConclusionThe use of quality control samples for batch correction leads to good results when enough QCs are available. If an experiment is properly set up, batch correction using the study samples usually leads to a similar high-quality correction, but has the advantage that more metabolites are corrected. The strategy for handling non-detects is important: choosing small values like zero can lead to suboptimal batch corrections.

ABSTRACT:A generalized expression is given for the similarity of spectra, based on the normalized integral of a weighted crosscorrelation function. It is shown that various similarity and dissimilarity criteria previously described in literature can be written as special cases of this general expression. A new similarity criterion, based on this generalized expression, is introduced. The benefits of this criterion are that it properly recognizes shifted but otherwise similar details in spectra and that the resulting similarity measure is normalized. Moreover, the criterion can easily be adapted to specific properties of spectra resulting from various analytical methods. The new criterion is applied to the classification of a series of crystal structures of cephalosporin complexes, based on comparison of their calculated powder diffraction patterns. The results are compared with those obtained using previously described criteria.

In order to better understand the milk proteome and its changes from colostrum to mature milk, samples taken at seven time points in the first 9 days from 4 individual cows were analyzed using proteomic techniques. Both the similarity in changes from day 0 to day 9 in the quantitative milk proteome, and the differences in specific protein abundance, were observed among four cows. One third of the quantified proteins showed a significant decrease in concentration over the first 9 days after calving, especially in the immune proteins (as much as 40 fold). Three relative high abundant enzymes (XDH, LPL, and RNASE1) and cell division and proliferation protein (CREG1) may be involved in the maturation of the gastro-intestinal tract. In addition, high correlations between proteins involved in complement and blood coagulation cascades illustrates the complex nature of biological interrelationships between milk proteins. The linear decrease of protease inhibitors and proteins involved in innate and adaptive immune system implies a protective role for protease inhibitor against degradation. In conclusion, the results found in this study not only improve our understanding of the role of colostrum in both host defense and development of the newborn calf but also provides guidance for the improvement of infant formula through better understanding of the complex interactions between milk proteins.

To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother’s SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother’s SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups as compared to the nonsecretor group. On the basis of the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided into two subgroups. HMOs that differed in level between Se+Le+ subgroups were 2′FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2′FL, LNT, and F-LNO as the driving force.