Evidence map›Paper›PMID 41057364›Full record

ArticleNature communications2025

HALO: hierarchical causal modeling for single cell multi-omics data.

Haiyi Mao, Minxue Jia, Marissa Di, Eleanor Valenzi, Xiaoyu Tracy Cai, Robert Lafyatis, Kun Zhang, Panayiotis V Benos

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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  3. Review
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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

8 authors.

Haiyi Mao *Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-5726-2613
Minxue Jia *Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9305-1218
Marissa Di *Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3740-129X
Eleanor ValenziDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-0656-6542
Xiaoyu Tracy CaiDepartment of Medicine, Loyola University Chicago, Chicago, IL, USA.
Robert LafyatisDivision of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9398-5034
Kun ZhangDepartment of Philosophy, Carnegie Mellon University, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-0738-9958
Panayiotis V BenosDepartment of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA. pbenos@ufl.edu.ORCID http://orcid.org/0000-0003-3172-3132

Funding

Systems Biology CoreP50AR080612 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robyn Therese Domsic · 2022 to 2026
$9.5M
Genomic Analysis of Tissue and Cellular Heterogeneity in IPFR01HL127349 · NHLBI · YALE UNIVERSITY · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2015 to 2025
$5.9M
Integrative Model of Metabolomics, Equol and Atherosclerotic cardiovascular disease (IMMEA)R01HL169332 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PANAGIOTIS V BENOS, AKIRA SEKIKAWA · 2024 to 2026
$2.0M
Interpretable graphical models for large multi-modal COPD data (R01HL159805)R01HL159805 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENOS, PANAGIOTIS V, SPIRTES, PETER · 2021 to 2024
$2.0M
EpiGNOME: Epigenetic Graphical Networks Of Methylation Effectors for COPD ProgressionR01HL178032 · NHLBI · UNIVERSITY OF FLORIDA · PI PANAGIOTIS V BENOS, DAWN L DEMEO · 2025 to 2026
$1.5M
Uncovering the genomic regulatory network of myofibroblast differentiation in systemic sclerosis-associated interstitial lung diseaseK08HL161258 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Eleanor Valenzi · 2022 to 2026
$806k
NHLBI NIH HHS K08 HL161258NHLBI NIH HHS R01 HL127349NHLBI NIH HHS R01 HL159805NHLBI NIH HHS R01 HL169332NHLBI NIH HHS R01 HL178032NIAMS NIH HHS P50 AR080612U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) K08HL161258U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL127349U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL159805U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL169332U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL178032U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P50AR080612
6 · The paper itself

Abstract

Though open chromatin may promote active transcription, gene expression responses may not be directly coordinated with changes in chromatin accessibility. Most existing methods for single-cell multi-omics data focus only on learning stationary, shared information among these modalities, overlooking modality-specific information delineating cellular states and dynamics resulting from causal relations among modalities. To address this, the epigenome-transcriptome relationship can be characterized in relation to time as coupled (changing dependently) or decoupled (changing independently). We propose the framework HALO, adopting a causal approach to model these temporal causal relations on two levels. On the representation level, HALO factorizes these two modalities into both coupled and decoupled latent representations, revealing their dynamic interplay. On the individual gene level, HALO matches gene-peak pairs and characterizes their changes over time. HALO discovers analogous biological functions between modalities, distinguishes epigenetic factors for lineage specification, and identifies temporal cis-regulation interactions relevant to cellular differentiation and human diseases.

Indexed as

Computational BiologySingle-Cell AnalysisCell DifferentiationChromatinEpigenesis, GeneticEpigenomeEpigenomicsGene Expression ProfilingHumansMultiomicsTranscriptomeChromatin

Identifiers

PMID41057364
PMCPMC12504611

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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.