Evidence map›Paper›PMID 27634930›Full record

ArticleNucleic acids research2017

Methods to increase reproducibility in differential gene expression via meta-analysis.

Timothy E Sweeney, Winston A Haynes, Francesco Vallania, John P Ioannidis, Purvesh Khatri

Abstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 12 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

85 citing papers in PubMed, 12 syntheses or guidelines pooled it.

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25 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

5 authors.

Timothy E SweeneyStanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-3596-1093
Winston A HaynesBiomedical Informatics Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Francesco VallaniaStanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
John P IoannidisDepartment of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA.
Purvesh KhatriStanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA pkhatri@stanford.edu.

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5M
TrainingU54AI117925 · NIAID · STANFORD UNIVERSITY · PI MUSEN, MARK A · 2014 to 2018
$12.9M
Integrative Omics as a Discovery Tool for Pulmonary HypertensionR01HL122887 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2015 to 2018
$4.1M
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 HL120001NHLBI NIH HHS R01 HL122887NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI109662NIAID NIH HHS U54 AI117925NLM NIH HHS T15 LM007033
6 · The paper itself

Abstract

Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a 'silver standard' of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini-Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size.

Indexed as

Gene Expression RegulationGenome, HumanMeta-Analysis as TopicModels, StatisticalAdenocarcinomaAdenocarcinoma of LungCardiomyopathiesCohort StudiesDatasets as TopicGene Expression ProfilingGenetic HeterogeneityGenome-Wide Association StudyGraft RejectionGuidelines as TopicHumansInfluenza, Human

Identifiers

PMID27634930
PMCPMC5224496

What OpenQuestion holds

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LicenceCC BY-NC
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.