ArticleStatistical methods in medical research2016
The limitations of simple gene set enrichment analysis assuming gene independence.
Article in Statistical methods in medical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Gene expression signatures of response to fluoxetine treatment: systematic review and meta-analyses.Molecular psychiatry · 2025Pooled it
- Random-effects meta-analysis of effect sizes as a unified framework for gene set analysis.PLoS computational biology · 2022Pooled it
- Knowledge-driven interpretable neural networks provide mechanistic insight.Genome research · 2026Article
- Primary ciliogenesis is promoted during epithelial-mesenchymal transition via a miR-200 - DZIP1 axis.Cell communication and signaling : CCS · 2026Article
- Circadian Dysfunction in the Skeletal Muscle Impairs Limb Perfusion and Muscle Regeneration in Peripheral Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Gene Set Enrichment Analysis in Zebrafish Embryos Is Susceptible to False-Positive Results in the Absence of Differentially Expressed Genes.Bioinformatics and biology insights · 2025Article
- Uncovering differential gene expression between mtRNA-positive and -negative osteosarcoma cells: implications beyond mitochondrial function.Frontiers in genetics · 2025Article
- Aphthous stomatitis - computational biology suggests external biotic stimulus and immunogenic cell death involved.BMC oral health · 2024Article
- Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.Cell reports · 2024Article
- GOAT: efficient and robust identification of gene set enrichment.Communications biology · 2024Article
- Article
- A Continuous Extension of Gene Set Enrichment Analysis Using the Likelihood Ratio Test Statistics Identifies Vascular Endothelial Growth Factor as a Candidate Pathway for Alzheimer's Disease via ITGA5.Journal of Alzheimer's disease : JAD · 2024Article
- Dynamic RNA Polymerase II Recruitment Drives Differentiation of the Intestine under the direction of HNF4.bioRxiv : the preprint server for biology · 2023Article
- TGFB1 induces fetal reprogramming and enhances intestinal regeneration.Cell stem cell · 2023Article
- Addressing erroneous scale assumptions in microbe and gene set enrichment analysis.PLoS computational biology · 2023Article
- Roastgsa: a comparison of rotation-based scores for gene set enrichment analysis.BMC bioinformatics · 2023Article
- Machine learning-based identification of cuproptosis-related markers and immune infiltration in severe community-acquired pneumonia.The clinical respiratory journal · 2023Article
- NaRnEA: An Information Theoretic Framework for Gene Set Analysis.Entropy (Basel, Switzerland) · 2023Article
- TGFB1 Induces Fetal Reprogramming and Enhances Intestinal Regeneration.bioRxiv : the preprint server for biology · 2023Article
- Hypergraph geometry reflects higher-order dynamics in protein interaction networks.Scientific reports · 2022Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Since its first publication in 2003, the Gene Set Enrichment Analysis method, based on the Kolmogorov-Smirnov statistic, has been heavily used, modified, and also questioned. Recently a simplified approach using a one-sample t-test score to assess enrichment and ignoring gene-gene correlations was proposed by Irizarry et al. 2009 as a serious contender. The argument criticizes Gene Set Enrichment Analysis's nonparametric nature and its use of an empirical null distribution as unnecessary and hard to compute. We refute these claims by careful consideration of the assumptions of the simplified method and its results, including a comparison with Gene Set Enrichment Analysis's on a large benchmark set of 50 datasets. Our results provide strong empirical evidence that gene-gene correlations cannot be ignored due to the significant variance inflation they produced on the enrichment scores and should be taken into account when estimating gene set enrichment significance. In addition, we discuss the challenges that the complex correlation structure and multi-modality of gene sets pose more generally for gene set enrichment methods.
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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.