Dataset Information

RRmix: A method for simultaneous batch effect correction and analysis of metabolomics data in the absence of internal standards.

ABSTRACT: With the surge of interest in metabolism and the appreciation of its diverse roles in numerous biomedical contexts, the number of metabolomics studies using liquid chromatography coupled to mass spectrometry (LC-MS) approaches has increased dramatically in recent years. However, variation that occurs independently of biological signal and noise (i.e. batch effects) in metabolomics data can be substantial. Standard protocols for data normalization that allow for cross-study comparisons are lacking. Here, we investigate a number of algorithms for batch effect correction and differential abundance analysis, and compare their performance. We show that linear mixed effects models, which account for latent (i.e. not directly measurable) factors, produce satisfactory results in the presence of batch effects without the need for internal controls or prior knowledge about the nature and sources of unwanted variation in metabolomics data. We further introduce an algorithm-RRmix-within the family of latent factor models and illustrate its suitability for differential abundance analysis in the presence of strong batch effects. Together this analysis provides a framework for systematically standardizing metabolomics data.

SUBMITTER: Salerno S

PROVIDER: S-EPMC5491020 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

RRmix: A method for simultaneous batch effect correction and analysis of metabolomics data in the absence of internal standards.

Salerno Stephen S Mehrmohamadi Mahya M Liberti Maria V MV Wan Muting M Wells Martin T MT Booth James G JG Locasale Jason W JW

PloS one 20170629 6

With the surge of interest in metabolism and the appreciation of its diverse roles in numerous biomedical contexts, the number of metabolomics studies using liquid chromatography coupled to mass spectrometry (LC-MS) approaches has increased dramatically in recent years. However, variation that occurs independently of biological signal and noise (i.e. batch effects) in metabolomics data can be substantial. Standard protocols for data normalization that allow for cross-study comparisons are lackin ...[more]

PMID: 28662051

Similar Datasets

Project description:BACKGROUND: Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To date, little attention has been given to issues related to normalization and batch effect correction for this kind of data. METHODS: We evaluated three common normalization approaches and investigated their performance in batch effect removal using three datasets with different degrees of batch effects generated from HumanMethylation27 platform: quantile normalization at average ? value (QN?); two step quantile normalization at probe signals implemented in "lumi" package of R (lumi); and quantile normalization of A and B signal separately (ABnorm). Subsequent Empirical Bayes (EB) batch adjustment was also evaluated. RESULTS: Each normalization could remove a portion of batch effects and their effectiveness differed depending on the severity of batch effects in a dataset. For the dataset with minor batch effects (Dataset 1), normalization alone appeared adequate and "lumi" showed the best performance. However, all methods left substantial batch effects intact in the datasets with obvious batch effects and further correction was necessary. Without any correction, 50 and 66 percent of CpGs were associated with batch effects in Dataset 2 and 3, respectively. After QN?, lumi or ABnorm, the number of CpGs associated with batch effects were reduced to 24, 32, and 26 percent for Dataset 2; and 37, 46, and 35 percent for Dataset 3, respectively. Additional EB correction effectively removed such remaining non-biological effects. More importantly, the two-step procedure almost tripled the numbers of CpGs associated with the outcome of interest for the two datasets. CONCLUSION: Genome-wide methylation data from Infinium Methylation BeadChip can be susceptible to batch effects with profound impacts on downstream analyses and conclusions. Normalization can reduce part but not all batch effects. EB correction along with normalization is recommended for effective batch effect removal.

Project description:In recent years, mass spectrometry-based metabolomics has increasingly been applied to large-scale epidemiological studies of human subjects. However, the successful use of metabolomics in this context is subject to the challenge of detecting biologically significant effects despite substantial intensity drift that often occurs when data are acquired over a long period or in multiple batches. Numerous computational strategies and software tools have been developed to aid in correcting for intensity drift in metabolomics data, but most of these techniques are implemented using command-line driven software and custom scripts which are not accessible to all end users of metabolomics data. Further, it has not yet become routine practice to assess the quantitative accuracy of drift correction against techniques which enable true absolute quantitation such as isotope dilution mass spectrometry. We developed an Excel-based tool, MetaboDrift, to visually evaluate and correct for intensity drift in a multi-batch liquid chromatography - mass spectrometry (LC-MS) metabolomics dataset. The tool enables drift correction based on either quality control (QC) samples analyzed throughout the batches or using QC-sample independent methods. We applied MetaboDrift to an original set of clinical metabolomics data from a mixed-meal tolerance test (MMTT). The performance of the method was evaluated for multiple classes of metabolites by comparison with normalization using isotope-labeled internal standards. QC sample-based intensity drift correction significantly improved correlation with IS-normalized data, and resulted in detection of additional metabolites with significant physiological response to the MMTT. The relative merits of different QC-sample curve fitting strategies are discussed in the context of batch size and drift pattern complexity. Our drift correction tool offers a practical, simplified approach to drift correction and batch combination in large metabolomics studies.

Dataset Information

RRmix: A method for simultaneous batch effect correction and analysis of metabolomics data in the absence of internal standards.

Publications

RRmix: A method for simultaneous batch effect correction and analysis of metabolomics data in the absence of internal standards.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets