Evidence map›Paper›PMID 35292087›Full record

ArticleGenome biology2022

Exaggerated false positives by popular differential expression methods when analyzing human population samples.

Yumei Li, Xinzhou Ge, Fanglue Peng, Wei Li, Jingyi Jessica Li

Abstract read
In one paragraph

Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
185citing 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

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

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Article
  7. SIEVEseq: unified differential expression, variability, and skewness analyses using RNA-Seq data.DNA research : an international journal for rapid publication of reports on genes and genomes · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

125 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Yumei Li *Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, 92697, USA.
Xinzhou Ge *Department of Statistics, University of California, Los Angeles, CA, 90095, USA.
Fanglue PengDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Wei LiDivision of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, 92697, USA. wei.li@uci.edu.
Jingyi Jessica LiDepartment of Statistics, University of California, Los Angeles, CA, 90095, USA. lijy03@g.ucla.edu.ORCID http://orcid.org/0000-0002-9288-5648

Funding

Computational and Experimental Modeling of Alternative PolyadenylationR01CA193466 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2016 to 2025
$3.3M
Transfer: DNA Methylation Canyons in Human Cancers: Methods, Target Genes and Functional ConsequencesR01CA228140 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LI, WEI · 2019 to 2023
$2.8M
Statistical Methods for Elucidating Regulatory Mechanisms and Functional Impacts of Transcriptome Variation at Population and Single-Cell ScalesR35GM140888 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, JINGYI JESSICA · 2021 to 2025
$2.0M
Robust Identification and accurate quantification of RNA transcripts on a system wide scaleR01GM120507 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, JINGYI JESSICA · 2016 to 2021
$1.7M
NCI NIH HHS R01CA193466NCI NIH HHS R01 CA228140NCI NIH HHS R01CA228140NIGMS NIH HHS R01 GM120507NIGMS NIH HHS R35 GM140888
6 · The paper itself

Abstract

When identifying differentially expressed genes between two conditions using human population RNA-seq samples, we found a phenomenon by permutation analysis: two popular bioinformatics methods, DESeq2 and edgeR, have unexpectedly high false discovery rates. Expanding the analysis to limma-voom, NOISeq, dearseq, and Wilcoxon rank-sum test, we found that FDR control is often failed except for the Wilcoxon rank-sum test. Particularly, the actual FDRs of DESeq2 and edgeR sometimes exceed 20% when the target FDR is 5%. Based on these results, for population-level RNA-seq studies with large sample sizes, we recommend the Wilcoxon rank-sum test.

Indexed as

Computational BiologyGene Expression ProfilingHumansRNA-SeqSample SizeSequence Analysis, RNA

Identifiers

PMID35292087
PMCPMC8922736

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.