Evidence map›Paper›PMID 32321923›Full record

ArticleNature communications2020

Consistent RNA sequencing contamination in GTEx and other data sets.

Tim O Nieuwenhuis, Stephanie Y Yang, Rohan X Verma, Vamsee Pillalamarri, Dan E Arking, Avi Z Rosenberg, Matthew N McCall, Marc K Halushka

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Targeted decontamination of sequencing data with CLEAN.NAR genomics and bioinformatics · 2025
    Article
  6. Review
  7. Beyond the Bubble: A Debate on microRNA Sorting Into Extracellular Vesicles.Laboratory investigation; a journal of technical methods and pathology · 2025
    Review
  8. Article
  9. Patterns of Unwanted Biological and Technical Expression Variation Among 49 Human Tissues.Laboratory investigation; a journal of technical methods and pathology · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. TargetedCell reports methods · 2023
    Article
  18. Article
  19. ElasticBLAST: Accelerating Sequence Search via Cloud Computing.bioRxiv : the preprint server for biology · 2023
    Article
  20. Article
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

8 authors.

Tim O NieuwenhuisDepartment of Pathology, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Stephanie Y YangMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Rohan X VermaDepartment of Pathology, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Vamsee PillalamarriMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Avi Z RosenbergDepartment of Pathology, Johns Hopkins University SOM, Baltimore, MD, 21205, USA.
Matthew N McCallDepartment of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Marc K HalushkaDepartment of Pathology, Johns Hopkins University SOM, Baltimore, MD, 21205, USA. mhalush1@jhmi.edu.ORCID http://orcid.org/0000-0002-7112-7389

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
VISUAL INDICES OF NEUROTOXICITYP30ES001247 · NIEHS · UNIVERSITY OF ROCHESTER · PI Sally W Thurston · 1985 to 2026
$42.8M
The University of Rochester's Clinical and Translational Science InstituteUL1TR002001 · NCATS · UNIVERSITY OF ROCHESTER · PI WILSON, KAREN M., ZAND, MARTIN S · 2016 to 2024
$34.6M
Predoctoral Training Program in Human GeneticsT32GM007814 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 1985 to 2021
$10.6M
Mitochondrial DNA Copy Number and Genetic Variation in Coronary Heart DiseaseR01HL131573 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ARKING, DAN E · 2016 to 2019
$3.2M
Fine Dissection of Atherosclerosis Microenvironment RNA ExpressionR01HL137811 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HALUSHKA, MARC K · 2017 to 2020
$2.4M
xMD-miRNA-Seq estimates cell-specific miRNA expressionR01GM130564 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HALUSHKA, MARC K · 2018 to 2021
$1.2M
NCATS NIH HHS UL1 TR002001NCI NIH HHS P30 CA006973NHLBI NIH HHS R01 HL131573NHLBI NIH HHS R01 HL137811NIEHS NIH HHS P30 ES001247NIGMS NIH HHS R01 GM130564NIGMS NIH HHS T32 GM007814
6 · The paper itself

Abstract

A challenge of next generation sequencing is read contamination. We use Genotype-Tissue Expression (GTEx) datasets and technical metadata along with RNA-seq datasets from other studies to understand factors that contribute to contamination. Here we report, of 48 analyzed tissues in GTEx, 26 have variant co-expression clusters of four highly expressed and pancreas-enriched genes (PRSS1, PNLIP, CLPS, and/or CELA3A). Fourteen additional highly expressed genes from other tissues also indicate contamination. Sample contamination is strongly associated with a sample being sequenced on the same day as a tissue that natively expresses those genes. Discrepant SNPs across four contaminating genes validate the contamination. Low-level contamination affects ~40% of samples and leads to numerous eQTL assignments in inappropriate tissues among these 18 genes. This type of contamination occurs widely, impacting bulk and single cell (scRNA-seq) data set analysis. In conclusion, highly expressed, tissue-enriched genes basally contaminate GTEx and other datasets impacting analyses.

Indexed as

DNA ContaminationGenotypeHigh-Throughput Nucleotide SequencingHumansPolymorphism, Single NucleotideRNASequence Analysis, RNASingle-Cell AnalysisRNA

Identifiers

PMID32321923
PMCPMC7176728

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.