Evidence map›Paper›PMID 31164141›Full record

ArticleGenome biology2019

A practical guide to methods controlling false discoveries in computational biology.

Keegan Korthauer, Patrick K Kimes, Claire Duvallet, Alejandro Reyes, Ayshwarya Subramanian, Mingxiang Teng, Chinmay Shukla, Eric J Alm, Stephanie C Hicks

Abstract readComparative StudyEvaluation Study
In one paragraph

Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
257citing papers in PubMed, 3 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

257 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Polygenic Risk and Nutrient Intake Interactions on Obesity Outcomes: A Systematic Review and Meta-Analysis of Observational Studies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Pooled it
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  4. Sleeping for Two: a randomized controlled trial of cognitive behavioral therapy for insomnia in pregnancy.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025
    Trial
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  9. Translational cancer research · 2026
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  19. Review
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197 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

9 authors.

Keegan KorthauerDepartment of Data Sciences, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, USA.
Patrick K KimesDepartment of Data Sciences, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, USA.
Claire DuvalletDepartment of Biological Engineering, MIT, 77 Massachusetts Avenue, Cambridge, USA.
Alejandro ReyesDepartment of Data Sciences, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, USA.
Ayshwarya SubramanianBroad Institute, 415 Main Street, Cambridge, USA.
Mingxiang TengDepartment of Biostatistics & Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, 33612, USA.
Chinmay ShuklaBiological and Biomedical Sciences Program, Harvard University, Boston, USA.
Eric J AlmDepartment of Biological Engineering, MIT, 77 Massachusetts Avenue, Cambridge, USA.
Stephanie C HicksDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, 21205, USA. shicks19@jhu.edu.ORCID http://orcid.org/0000-0002-7858-0231

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Project-002U41HG004059 · NHGRI · ROSWELL PARK CANCER INSTITUTE CORP · PI MORGAN, MARTIN T · 2011 to 2020
$13.2M
Preprocessing and Analysis Tools for High-Throughput TechnologiesR01GM083084 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2007 to 2018
$4.4M
Overcoming bias and unwanted variability in next generation sequencingR01HG005220 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2010 to 2018
$3.6M
Software for the statistical analysis of microarray probe level dataR01GM103552 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2012 to 2013
$735k
Statistical Methods for the Normalization and Quantification of Single-Cell RNA-Sequencing DataR00HG009007 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI HICKS, STEPHANIE CARINNE · 2018 to 2020
$725k
Statistical Methods for the Normalization and Quantification of Single-Cell RNA-Sequencing DataK99HG009007 · NHGRI · DANA-FARBER CANCER INST · PI HICKS, STEPHANIE CARINNE · 2017 to 2018
$124k
NCI NIH HHS P30 CA076292NHGRI NIH HHS R00 HG009007NHGRI NIH HHS R01 HG005220NHGRI NIH HHS U41 HG004059NIGMS NIH HHS R01 GM083084NIGMS NIH HHS R01 GM103552
6 · The paper itself

Abstract

backgroundIn high-throughput studies, hundreds to millions of hypotheses are typically tested. Statistical methods that control the false discovery rate (FDR) have emerged as popular and powerful tools for error rate control. While classic FDR methods use only p values as input, more modern FDR methods have been shown to increase power by incorporating complementary information as informative covariates to prioritize, weight, and group hypotheses. However, there is currently no consensus on how the modern methods compare to one another. We investigate the accuracy, applicability, and ease of use of two classic and six modern FDR-controlling methods by performing a systematic benchmark comparison using simulation studies as well as six case studies in computational biology.

resultsMethods that incorporate informative covariates are modestly more powerful than classic approaches, and do not underperform classic approaches, even when the covariate is completely uninformative. The majority of methods are successful at controlling the FDR, with the exception of two modern methods under certain settings. Furthermore, we find that the improvement of the modern FDR methods over the classic methods increases with the informativeness of the covariate, total number of hypothesis tests, and proportion of truly non-null hypotheses.

conclusionsModern FDR methods that use an informative covariate provide advantages over classic FDR-controlling procedures, with the relative gain dependent on the application and informativeness of available covariates. We present our findings as a practical guide and provide recommendations to aid researchers in their choice of methods to correct for false discoveries.

Indexed as

Computational BiologyComputer SimulationChIP-seqFalse discovery rateGene set analysisGWASMicrobiomeMultiple hypothesis testingRNA-seqScRNA-seq

Identifiers

PMID31164141
PMCPMC6547503

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.