Evidence map›Paper›PMID 29929481›Full record

ArticleBMC bioinformatics2018

Gene length corrected trimmed mean of M-values (GeTMM) processing of RNA-seq data performs similarly in intersample analyses while improving intrasample comparisons.

Marcel Smid, Robert R J Coebergh van den Braak, Harmen J G van de Werken, Job van Riet, Anne van Galen, Vanja de Weerd, Michelle van der Vlugt-Daane, Sandra I Bril, Zarina S Lalmahomed, Wigard P Kloosterman and 6 more

Abstract read
In one paragraph

Article in BMC bioinformatics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing 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

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

  1. Pooled it
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  20. Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular function.Clinical research in cardiology : official journal of the German Cardiac Society · 2025
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58 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

16 authors.

Marcel SmidDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands. m.smid@erasmusmc.nl.
Robert R J Coebergh van den BraakDepartment of Surgery, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Harmen J G van de WerkenCancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Job van RietCancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Anne van GalenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Vanja de WeerdDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Michelle van der Vlugt-DaaneDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Sandra I BrilDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Zarina S LalmahomedDepartment of Surgery, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Wigard P KloostermanDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Saskia M WiltingDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
John A FoekensDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Jan N M IJzermansDepartment of Surgery, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
MATCH study group
John W M MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.
Anieta M SieuwertsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center, 3015 CE, Rotterdam, The Netherlands.

Funding

European Research Council 322737
6 · The paper itself

Abstract

backgroundCurrent normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and validation of gene signatures. Most studies on optimization of normalization methods typically use simulated data to validate methodologies. We describe a new method, GeTMM, which allows for both inter- and intrasample analyses with the same normalized data set. We used actual (i.e. not simulated) RNA-seq data from 263 colon cancers (no biological replicates) and used the same read count data to compare GeTMM with the most commonly used normalization methods (i.e. TMM (used by edgeR), RLE (used by DESeq2) and TPM) with respect to distributions, effect of RNA quality, subtype-classification, recurrence score, recall of DE genes and correlation to RT-qPCR data.

resultsWe observed a clear benefit for GeTMM and TPM with regard to intrasample comparison while GeTMM performed similar to TMM and RLE normalized data in intersample comparisons. Regarding DE genes, recall was found comparable among the normalization methods, while GeTMM showed the lowest number of false-positive DE genes. Remarkably, we observed limited detrimental effects in samples with low RNA quality.

conclusionsWe show that GeTMM outperforms established methods with regard to intrasample comparison while performing equivalent with regard to intersample normalization using the same normalized data. These combined properties enhance the general usefulness of RNA-seq but also the comparability to the many array-based gene expression data in the public domain.

Indexed as

Gene Expression ProfilingHumansRNASequence Analysis, RNARNAColorectal CancerDESeq2edgeRGeTMMNormalization methodsRNA sequencingTPM

Identifiers

PMID29929481
PMCPMC6013957

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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.