Evidence map›Paper›PMID 33774420›Full record

ReviewComputational biology and chemistry2021

Beyond standard pipeline and p < 0.05 in pathway enrichment analyses.

Wentian Li, Andrew Shih, Yun Freudenberg-Hua, Wen Fury, Yaning Yang

Abstract readReview
In one paragraph

Review in Computational biology and chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

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

  1. Pooled it
  2. Article
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  4. Review
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  6. Review
  7. Article
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  9. Article
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  11. Deciphering the Role of CD14 inJournal of Cancer · 2025
    Article
  12. Article
  13. Blood-Type-A is a COVID-19 infection and hospitalization risk in a Turkish cohort.Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine · 2023
    Article
  14. 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.

Wentian LiThe Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Andrew ShihThe Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Yun Freudenberg-HuaLitwin-Zucker Center for the study of Alzheimer's Disease, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA; Division of Geriatric Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
Wen FuryRegeneron Pharmaceutical Inc., Tarrytown, NY, USA.
Yaning YangDepartment of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, China.

Funding

Identification of Risk Genes SupplementK08AG054727 · NIA · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI FREUDENBERG-HUA, YUN · 2017 to 2022
$739k
NIA NIH HHS K08 AG054727
6 · The paper itself

Abstract

A standard pathway/gene-set enrichment analysis, the over-representation analysis, is based on four values: the size of two gene-sets, size of their overlap, and size of the gene universe from which the gene-sets are chosen. The standard result of such an analysis is based on the p-value of a statistical test. We supplement this standard pipeline by six cautions: (1) any p-value threshold to distinguish enriched gene-sets from not-enriched ones is to certain degree arbitrary; (2) genes in a gene-set may be correlated, which potentially overcount the gene-set size; (3) any attempt to impose multiple testing correction will increase the false negative rate; (4) gene-sets in a gene-set database may be correlated, potentially overcount the factor for multiple testing correction; (5) the discrete nature of the data make it possible that a minimum change in counts may lead to a quantum change in the p-value threshold-based conclusion; (6) the two gene-sets may not be chosen from the universe of all human genes, but in fact from a subset of that universe, or even two different subsets of all genes. Careful reconsideration of these issues can have an impact on an enrichment analysis conclusion. Part of our cautions mirror the call from statistician that reaching conclusion from data is not a simple matter of p-value smaller than 0.05, but a thoughtful process with due diligences.

Indexed as

AlgorithmsComputational BiologyDatabases, GeneticGene Expression ProfilingHumansGene-set enrichmentHuman genesPathway analysisPipelinesStatistical significance

Identifiers

PMID33774420
PMCPMC9179938

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.