Evidence map›Paper›PMID 27272489›Full record

Observational studyPloS one2016

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data.

Christian Müller, Arne Schillert, Caroline Röthemeier, David-Alexandre Trégouët, Carole Proust, Harald Binder, Norbert Pfeiffer, Manfred Beutel, Karl J Lackner, Renate B Schnabel and 5 more

Abstract readObservational Study
In one paragraph

Observational study in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  8. A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Christian MüllerClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany.
Arne SchillertInstitute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein, Campus Luebeck, Lübeck, 23562, Germany.
Caroline RöthemeierClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany.
David-Alexandre TrégouëtInstitut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche(UMR) enSanté 1166, F-75013, Paris, France.
Carole ProustInstitut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche(UMR) enSanté 1166, F-75013, Paris, France.
Harald BinderInstitute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, Germany.
Norbert PfeifferExperimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University, Mainz, 55131, Germany.
Manfred BeutelDepartment of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Karl J LacknerInstitute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.
Renate B SchnabelClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany.
Laurence TiretInstitut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche(UMR) enSanté 1166, F-75013, Paris, France.
Philipp S WildPreventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Mainz, 55131, Germany.
Stefan BlankenbergClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany.
Tanja ZellerClinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, 20246, Germany.
Andreas ZieglerInstitute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein, Campus Luebeck, Lübeck, 23562, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data.

Indexed as

AdultAgedFemaleGene Expression ProfilingHumansLongitudinal StudiesMaleMiddle AgedMonocytesNonlinear DynamicsOligonucleotide Array Sequence AnalysisPrincipal Component AnalysisProspective Studies

Identifiers

PMID27272489
PMCPMC4896498

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.