Evidence map›Paper›PMID 42818071›Full record

ArticlebioRxiv : the preprint server for biology2026

CardioChrom Reconstructs the Human Cardiac Virtual Epigenome from Single-Nucleus Transcriptomes.

Hongbiao Huang, Xiaodan Hui, Yingjian Li, Ahmed Abdelbaset-Ismail, Zixuan Xu, Suchen Yadav, Yi Tan

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Hongbiao HuangPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.ORCID 0000-0002-5420-3415
Xiaodan HuiPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
Yingjian LiPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
Ahmed Abdelbaset-IsmailPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
Zixuan XuPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
Suchen YadavPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.
Yi TanPhoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.

Funding

Fibroblast Growth Factor 1 Prevents Hyperlipidemia and atherosclerosisR01HL160927 · NHLBI · UNIVERSITY OF LOUISVILLE · PI Yi Tan · 2022 to 2026
$2.7M
Dual targeting chemokine receptors prevents chemotherapy-induced cardiotoxicityR01HL174922 · NHLBI · UNIVERSITY OF LOUISVILLE · PI Yi Tan · 2024 to 2026
$2.0M
A novel mechanism of stromal cell-derived factor 1 protection against diabetic cardiomyopathyR01HL125877 · NHLBI · UNIVERSITY OF LOUISVILLE · PI TAN, YI · 2017 to 2021
$1.9M
Cardiokine FGF16 prevents diabetic cardiomyopathyR01HL179184 · NHLBI · UNIVERSITY OF ARIZONA · PI Yi Tan · 2026 to 2026
$754k
NHLBI NIH HHS R01 HL125877NHLBI NIH HHS R01 HL160927NHLBI NIH HHS R01 HL174922NHLBI NIH HHS R01 HL179184
6 · The paper itself

Abstract

Background: Matched epigenomic profiling remains scarce in human heart failure, limiting regulatory interpretation of single-nucleus ribonucleic acid (RNA) sequencing data. We developed CardioChrom, a cardiac-specialized framework that reconstructs chromatin accessibility, histone H3 lysine 27 acetylation (H3K27ac), and histone H3 lysine 27 trimethylation (H3K27me3) from single-nucleus RNA profiles. Methods: CardioChrom was developed using same-nucleus human heart datasets jointly measuring RNA with chromatin accessibility by assay for transposase-accessible chromatin (ATAC), H3K27ac, or H3K27me3, with donor-separated development and leave-one-cell-type-out testing. Frozen models were evaluated in 10-donor and 23-sample external human heart cohorts. Histone reconstruction was benchmarked against measured profiles and a Transformer. The models were then applied without refitting to an RNA-only cohort of 43 donors with heart failure with preserved ejection fraction (HFpEF). Results: Across unseen cardiac cell types, CardioChrom increased area under the precision-recall curve by 0.0109 relative to within-cell-type RNA shuffling in 11 of 12 cell types and increased area under the receiver operating characteristic curve by 0.0179 in all 12. CardioChrom exceeded controls in both external cohorts and matched or exceeded the Transformer across 6 prespecified histone metrics. In HFpEF, 3,581 donor-level pathway-layer associations met global false discovery rate, sex-adjustment, and leave-one-donor-out robustness criteria. Endothelial cells showed prominent reconstructed histone-associated changes involving coagulation, inflammation, hypoxia, and profibrotic signaling. Von Willebrand factor expression and its reconstructed regulatory states were consistently reduced, and all 6 linked candidate cis-regulatory elements were classified as repressed. Motif-supported TF-cCRE-gene hypotheses were generated in endothelial cells and fibroblasts. Conclusions: CardioChrom extends RNA-only human heart failure cohorts toward cell-type-resolved virtual epigenomic and regulatory analysis while distinguishing predictions from direct measurements.

Indexed as

chromatin accessibilityHeart failureHFpEFhistone modificationsingle-nucleus RNA sequencingvirtual epigenome

Identifiers

PMID42818071
PMCPMC13622052

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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.