Evidence map›Paper›PMID 20955544›Full record

ArticleBMC genomics2010

Heading down the wrong pathway: on the influence of correlation within gene sets.

Daniel M Gatti, William T Barry, Andrew B Nobel, Ivan Rusyn, Fred A Wright

Abstract read
In one paragraph

Article in BMC genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
–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

49 citing papers in PubMed.

  1. Article
  2. A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Test-statistic correlation and data-row correlation.Statistics & probability letters · 2020
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

5 authors.

Daniel M GattiDepartment of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
William T Barry
Andrew B Nobel
Ivan Rusyn
Fred A Wright

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Bioengineering partnership to improve chemical hazard testing paradigmsR01ES015241 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUSYN, IVAN · 2008 to 2012
$3.1M
FACILITATING GTEx, DISEASE, AND GxE ANALYSES VIA FAST EXPRESSION (e)QTL MAPPINGR01MH090936 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NOBEL, ANDREW B, RUSYN, IVAN · 2010 to 2012
$847k
NIEHS NIH HHS P30 ES010126NIEHS NIH HHS R01 ES015241NIMH NIH HHS R01 MH090936
6 · The paper itself

Abstract

backgroundAnalysis of microarray experiments often involves testing for the overrepresentation of pre-defined sets of genes among lists of genes deemed individually significant. Most popular gene set testing methods assume the independence of genes within each set, an assumption that is seriously violated, as extensive correlation between genes is a well-documented phenomenon.

resultsWe conducted a meta-analysis of over 200 datasets from the Gene Expression Omnibus in order to demonstrate the practical impact of strong gene correlation patterns that are highly consistent across experiments. We show that a common independence assumption-based gene set testing procedure produces very high false positive rates when applied to data sets for which treatment groups have been randomized, and that gene sets with high internal correlation are more likely to be declared significant. A reanalysis of the same datasets using an array resampling approach properly controls false positive rates, leading to more parsimonious and high-confidence gene set findings, which should facilitate pathway-based interpretation of the microarray data.

conclusionsThese findings call into question many of the gene set testing results in the literature and argue strongly for the adoption of resampling based gene set testing criteria in the peer reviewed biomedical literature.

Indexed as

Databases, GeneticAnimalsGene Expression RegulationHumansMiceOligonucleotide Array Sequence AnalysisPublications

Identifiers

PMID20955544
PMCPMC3091509

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.