Evidence map›Paper›PMID 35151364›Full record

ArticleBioData mining2022

Gene-Interaction-Sensitive enrichment analysis in congenital heart disease.

Alexa A Woodward, Deanne M Taylor, Elizabeth Goldmuntz, Laura E Mitchell, A J Agopian, Jason H Moore, Ryan J Urbanowicz

Open access · goldAbstract read
In one paragraph

Article in BioData mining, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 46% of its field
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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Systemic lupus erythematosus with high disease activity identification based on machine learning.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  3. Nine quick tips for pathway enrichment analysis.PLoS computational biology · 2022
    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

7 authors at 4 institutions in 1 country.

Alexa A WoodwardDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Deanne M TaylorChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Elizabeth GoldmuntzChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Laura E MitchellHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.
A J AgopianHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.
Jason H MooreDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ryan J UrbanowiczDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. ryanurb@upenn.edu.ORCID http://orcid.org/0000-0002-0487-5555
Cedars-Sinai Medical Center · USChildren's Hospital of Philadelphia · USUniversity of Texas Health Science Center at Dallas · USUniversity of Pennsylvania · US

Funding

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR024134 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$70.4M
Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
Molecular Analysis of Human Subtelomeric RearrangementsP50HL074731 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI LEVY, ROBERT J · 2004 to 2008
$19.2M
Project 2: Genetic Mechanisms of Non-syndromic Congenital Cardiac DefectsP01HD070454 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI MORROW, BERNICE E · 2011 to 2020
$14.0M
Training Program in Computational GenomicsT32HG000046 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI JUNHYONG KIM, Mingyao Li · 1999 to 2026
$9.5M
Bioinformatics Strategies for Genome-Wide Association StudiesR01LM010098 · NLM · UNIVERSITY OF PENNSYLVANIA · PI MOORE, JASON H., WILLIAMS, SCOTT MATTHEW · 2009 to 2023
$5.1M
Biomedical Computing and Informatics Strategies for Precision MedicineR01LM012601 · NLM · UNIVERSITY OF PENNSYLVANIA · PI HUANG, XIUZHEN, MOORE, JASON H. · 2017 to 2020
$1.8M
Rule-based machine learning to address heterogeneity in high-dimensional survival dataF31LM013583 · NLM · UNIVERSITY OF PENNSYLVANIA · PI WOODWARD, ALEXA ABIGAIL · 2021 to 2022
$71k
National Institute of Child Health and Human Development P01-HD070454National Institute of Child Health and Human Development P50-HL74731NCATS NIH HHS UL1 TR000003NCRR NIH HHS UL1 RR024134NHGRI NIH HHS HG000046-21NHGRI NIH HHS T32 HG000046NHLBI NIH HHS P50 HL074731NICHD NIH HHS P01 HD070454NLM NIH HHS F31 LM013583NLM NIH HHS R01 LM010098NLM NIH HHS R01 LM012601U.S. National Library of Medicine R01-LM010098U.S. National Library of Medicine R01-LM012601
6 · The paper itself

Abstract

backgroundGene set enrichment analysis (GSEA) uses gene-level univariate associations to identify gene set-phenotype associations for hypothesis generation and interpretation. We propose that GSEA can be adapted to incorporate SNP and gene-level interactions. To this end, gene scores are derived by Relief-based feature importance algorithms that efficiently detect both univariate and interaction effects (MultiSURF) or exclusively interaction effects (MultiSURF*). We compare these interaction-sensitive GSEA approaches to traditional χ

resultsIn the simulation study and for both CTD datasets, both Relief-based approaches to GSEA captured more relevant and significant gene ontology terms compared to the univariate GSEA. Key terms and themes of interest include cell adhesion, migration, and signaling. A leading edge analysis highlighted semaphorins and their receptors, the Slit-Robo pathway, and other genes with roles in the secondary heart field and outflow tract development.

conclusionsOur results indicate that interaction-sensitive approaches to enrichment analysis can improve upon traditional univariate GSEA. This approach replicated univariate findings and identified additional and more robust support for the role of the secondary heart field and cardiac neural crest cell migration in the development of CTDs.

Indexed as

Congenital heart diseaseEpistasisGene set enrichment analysisGWAS

Identifiers

PMID35151364
PMCPMC8841104
OpenAlexW4211039611

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.