Evidence map›Paper›PMID 36334690›Full record

ArticleCardiovascular pathology : the official journal of the Society for Cardiovascular Pathology

Systematic dissection, preservation, and multiomics in whole human and bovine hearts.

Jesse D Moreira, Adam C Gower, Liying Xue, Yuriy Alekseyev, Karan K Smith, Seung H Choi, Nir Ayalon, Melissa G Farb, Kenneth Tenan, Ashley LeClerc and 7 more

Open access · greenAbstract read
In one paragraph

Article in Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 51% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
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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

17 authors at 3 institutions in 1 country.

Jesse D MoreiraEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Adam C GowerDepartment of Medicine, Section of Computational Biomedicine, and Clinical and Translational Science Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Liying XueEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Yuriy AlekseyevDepartment of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Karan K SmithEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Seung H ChoiCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nir AyalonCardiovascular Medicine Section, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Melissa G FarbEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Kenneth TenanBU Microarray and Sequencing Resource, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Ashley LeClercBU Microarray and Sequencing Resource, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Daniel LevyPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medicine, Preventive Medicine & Epidemiology Section, Boston University Chobanian & Avedisian School of Medicine, Boston University and the National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Emelia J BenjaminDepartment of Medicine, Preventive Medicine & Epidemiology Section, Boston University Chobanian & Avedisian School of Medicine, Boston University and the National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA; Section of Cardiovascular Medicine, Boston Medical Center/Boston University Chobanian & Avedisian School of Medicine and Department of Epidemiology Boston University School of Public Health, Boston, MA, USA.
Marc E LenburgDepartment of Medicine, Section of Computational Biomedicine, and Clinical and Translational Science Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Richard N MitchellDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Robert F PaderaDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jessica L FettermanEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. Electronic address: jefetter@bu.edu.
Deepa M GopalEvans Department of Medicine and The Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA; Cardiovascular Medicine Section, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. Electronic address: dmgopal@bu.edu.
Boston University · USBrigham and Women's Hospital · USBroad Institute · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Multidisciplinary Training in Cardiovascular ResearchT32HL007224 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM, WAINFORD, RICHARD DAVID · 1985 to 2020
$12.3M
Determinants of obesity-associated insulin resistanceK23HL135394 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, MELISSA G · 2017 to 2021
$895k
Relations of Mitochondrial Genetic Variation and Function with Atrial FibrillationK01HL143142 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FETTERMAN, JESSICA L · 2019 to 2023
$757k
NCATS NIH HHS UL1 TR001430NHLBI NIH HHS K01 HL143142NHLBI NIH HHS K23 HL135394NHLBI NIH HHS R01 HL092577NHLBI NIH HHS T32 HL007224
6 · The paper itself

Abstract

objectivesWe sought to develop a rigorous, systematic protocol for the dissection and preservation of human hearts for biobanking that expands previous success in postmortem transcriptomics to multiomics from paired tissue.

backgroundExisting cardiac biobanks consist largely of biopsy tissue or explanted hearts in select diseases and are insufficient for correlating whole organ phenotype with clinical data.

methodsWe demonstrate optimal conditions for multiomics interrogation (ribonucleic acid (RNA) sequencing, untargeted metabolomics) in hearts by evaluating the effect of technical variables (storage solution, temperature) and simulated postmortem interval (PMI) on RNA and metabolite stability. We used bovine (n=3) and human (n=2) hearts fixed in PAXgene or snap-frozen with liquid nitrogen.

resultsUsing a paired Wald test, only two of the genes assessed were differentially expressed between left ventricular samples from bovine hearts stored in PAXgene at 0 and 12 hours PMI (FDR q<0.05). We obtained similar findings in human left ventricular samples, suggesting stability of RNA transcripts at PMIs up to 12 hours. Different library preparation methods (mRNA poly-A capture vs. rRNA depletion) resulted in similar quality metrics with both library preparations achieving >95% of reads properly aligning to the reference genomes across all PMIs for bovine and human hearts. PMI had no effect on RNA Integrity Number or quantity of RNA recovered at the time points evaluated. Of the metabolites identified (855 total) using untargeted metabolomics of human left ventricular tissue, 503 metabolites remained stable across PMIs (0, 4, 8, 12 hours). Most metabolic pathways retained several stable metabolites.

conclusionsOur data demonstrate a technically rigorous, reproducible protocol that will enhance cardiac biobanking practices and facilitate novel insights into human CVD. CONDENSED ABSTRACT: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Current biobanking practices insufficiently capture both the diverse array of phenotypes present in CVDs and the spatial heterogeneity across cardiac tissue sites. We have developed a rigorous and systematic protocol for the dissection and preservation of human cardiac biospecimens to enhance the availability of whole organ tissue for multiple applications. When combined with longitudinal clinical phenotyping, our protocol will enable multiomics in hearts to deepen our understanding of CVDs.

Indexed as

Biological Specimen BanksCardiovascular DiseasesAnimalsCattleHeartHumansMultiomicsRNARNABiobankCardiovascularMetabolomicsMultiomicsPostmortem intervalRNA-Seq

Identifiers

PMID36334690
PMCPMC10031913
OpenAlexW4307930662

What OpenQuestion holds

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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.