Evidence map›Paper›PMID 29572502›Full record

ArticleScientific reports2018

Interpretation of biological experiments changes with evolution of the Gene Ontology and its annotations.

Aurelie Tomczak, Jonathan M Mortensen, Rainer Winnenburg, Charles Liu, Dominique T Alessi, Varsha Swamy, Francesco Vallania, Shane Lofgren, Winston Haynes, Nigam H Shah and 2 more

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing 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

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

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. The Gene Ontology knowledgebase in 2026.Nucleic acids research · 2026
    Article
  9. A practical guide to functional enrichment analysis.Frontiers in bioinformatics · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. IntegratingCancers · 2025
    Article
  18. Article
  19. Article
  20. Unravelling the developmental toxicity of heavy metals using zebrafish as a model: a narrative review.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025
    Review

18 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

12 authors.

Aurelie TomczakStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.
Jonathan M MortensenStanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
Rainer WinnenburgStanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-2770-2809
Charles LiuStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.
Dominique T AlessiStanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
Varsha SwamyStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.
Francesco VallaniaStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0003-0098-249X
Shane LofgrenStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.
Winston HaynesStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-2376-0630
Nigam H ShahStanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-9385-7158
Mark A MusenStanford Center for Biomedical Informatics Research (BMIR), Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
Purvesh KhatriStanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA. pkhatri@stanford.edu.ORCID 0000-0002-4143-4708

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
Stanford Career Development Program in Omics of Lung DiseasesK12HL120001 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2013 to 2017
$1.3M
NHLBI NIH HHS K12 HL120001NIAID NIH HHS U19 AI109662
6 · The paper itself

Abstract

Gene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high throughput molecular data and generating hypotheses about underlying biological phenomena of experiments. However, the two building blocks of this analysis - the ontology and the annotations - evolve rapidly. We used gene signatures derived from 104 disease analyses to systematically evaluate how enrichment analysis results were affected by evolution of the GO over a decade. We found low consistency between enrichment analyses results obtained with early and more recent GO versions. Furthermore, there continues to be a strong annotation bias in the GO annotations where 58% of the annotations are for 16% of the human genes. Our analysis suggests that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time. Hence, researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.

Indexed as

Computational BiologyDatabases, GeneticEvolution, MolecularGene OntologyModels, GeneticMolecular Sequence AnnotationHumansReproducibility of Results

Identifiers

PMID29572502
PMCPMC5865181

What OpenQuestion holds

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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.