Evidence map›Paper›PMID 31469842›Full record

ArticlePloS one2019

Sequential analysis of myocardial gene expression with phenotypic change: Use of cross-platform concordance to strengthen biologic relevance.

Lee S Toni, Ian A Carroll, Kenneth L Jones, Jessica A Schwisow, Wayne A Minobe, Erin M Rodriguez, Natasha L Altman, Brian D Lowes, Edward M Gilbert, Peter M Buttrick and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Lee S ToniDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Ian A CarrollDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Kenneth L JonesDepartment of Pediatrics, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Jessica A SchwisowDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Wayne A MinobeDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Erin M RodriguezDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Natasha L AltmanDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.ORCID 0000-0002-4190-057X
Brian D LowesDivision of Cardiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Edward M GilbertDivision of Cardiology, University of Utah Medical Center, Salt Lake City, Utah, United States of America.
Peter M ButtrickDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
David P KaoDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.
Michael R BristowDivision of Cardiology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, Colorado, United States of America.ORCID 0000-0002-8860-4698
University of Colorado Anschutz Medical Campus · USARCA Biopharma (United States) · USUniversity of Nebraska Medical Center · USUniversity of Utah · US

Funding

POSTGRADUATE TRAINING IN CARDIOVASCULAR RESEARCHT32HL007822 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BUTTRICK, PETER N., LEINWAND, LESLIE ANNE · 1996 to 2023
$6.2M
Dynamic Expression Profiling in the Intact Human HeartR01HL071118 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BRISTOW, MICHAEL R. · 2002 to 2003
$304k
NHLBI NIH HHS R01 HL071118NHLBI NIH HHS T32 HL007822
6 · The paper itself

Abstract

objectivesTo investigate the biologic relevance of cross-platform concordant changes in gene expression in intact human failing/hypertrophied ventricular myocardium undergoing reverse remodeling.

backgroundInformation is lacking on genes and networks involved in remodeled human LVs, and in the associated investigative best practices.

methodsWe measured mRNA expression in ventricular septal endomyocardial biopsies from 47 idiopathic dilated cardiomyopathy patients, at baseline and after 3-12 months of β-blocker treatment to effect left ventricular (LV) reverse remodeling as measured by ejection fraction (LVEF). Cross-platform gene expression change concordance was investigated in reverse remodeling Responders (R) and Nonresponders (NR) using 3 platforms (RT-qPCR, microarray, and RNA-Seq) and two cohorts (All 47 subjects (A-S) and a 12 patient "Super-Responder" (S-R) subset of A-S).

resultsFor 50 prespecified candidate genes, in A-S mRNA expression 2 platform concordance (CcpT), but not single platform change, was directly related to reverse remodeling, indicating CcpT has biologic significance. Candidate genes yielded a CcpT (PCR/microarray) of 62% for Responder vs. Nonresponder (R/NR) change from baseline analysis in A-S, and ranged from 38% to 100% in S-R for PCR/microarray/RNA-Seq 2 platform comparisons. Global gene CcpT measured by microarray/RNA-Seq was less than for candidate genes, in S-R R/NR 17.5% vs. 38% (P = 0.036). For S-R global gene expression changes, both cross-cohort concordance (CccT) and CcpT yielded markedly greater values for an R/NR vs. an R-only analysis (by 22 fold for CccT and 7 fold for CcpT). Pathway analysis of concordant global changes for R/NR in S-R revealed signals for downregulation of multiple phosphoinositide canonical pathways, plus expected evidence of a β1-adrenergic receptor gene network including enhanced Ca2+ signaling.

conclusionsTwo-platform concordant change in candidate gene expression is associated with LV biologic effects, and global expression concordant changes are best identified in an R/NR design that can yield novel information.

Identifiers

PMID31469842
PMCPMC6716635
OpenAlexW2970522059

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.