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Peer-reviewedCC BY 4.0Frontiers in Immunology

Integrated multi-omics and machine learning identify core mechanobiology-associated immune genes in pulmonary arterial hypertension

  • Pei Wang1,2
  • Fangchao Zhao3,4
  • Ting Yang5
  • Yadong Yuan1
5 affiliations
  1. 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University
  2. 2Department of Emergency, The Second Hospital of Hebei Medical University
  3. 3Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University
  4. 4Department of Thoracic Surgery, The Second Hospital of Hebei Medical University
  5. 5Department of Gastroenterology, The Fifth Clinical Medical College of Shanxi Medical University
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Abstract

Background: Pulmonary arterial hypertension (PAH) involves vascular remodeling and altered mechanical signaling. The immune-associated transcriptomic changes accompanying this environment remain incompletely characterized.

Methods: We integrated bulk lung (GSE15197), PBMC (GSE33463), and single-cell RNA-seq (GSE169471) data using a curated set of 2, 537 mechanical-related genes. WGCNA, LASSO, random forest, and single-cell localization supported candidate prioritization. The four-gene panel was examined in a monocrotaline-induced PH rat model and PBMCs from 10 IPAH patients and 10 controls.

Results: PAH transcriptomes showed enrichment of stress-fiber, actomyosin, ECM, and immune-related programs. CD83, CD86, IL6, and TLR7 were prioritized, with compartment-dependent expression patterns. Single-cell data localized CD83/CD86 to myeloid/APC compartments and IL6 to endothelial/fibroblast populations; TLR7 was sparsely detected. In MCT-treated rat lungs, CD86 and TLR7 proteins increased, whereas CD83 and IL-6 decreased. Clinical PBMCs showed corresponding expression directions, and each gene had an AUC >0.7. The exploratory four-gene disease-state score achieved an internal cross-validated AUC of 0.765.

Conclusions: The four candidates provide a cellular and molecular context for investigating immune-stromal interactions in PAH, including responses to noninfectious vascular injury. The panel showed moderate internal discrimination. These findings support further clinical and functional investigation but do not establish direct mechanotransduction targets or a causal pathway linking mechanical stress to vascular inflammation.

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Cite

BibTeXRIS
BibTeX
@article{wang2026integrated,
  title = {{Integrated multi-omics and machine learning identify core mechanobiology-associated immune genes in pulmonary arterial hypertension}},
  author = {Pei Wang and Fangchao Zhao and Ting Yang and Yadong Yuan},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1867114},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1867114/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Integrated multi-omics and machine learning identify core mechanobiology-associated immune genes in pulmonary arterial hypertension
AU  - Pei Wang
AU  - Fangchao Zhao
AU  - Ting Yang
AU  - Yadong Yuan
PY  - 2026
DA  - 2026/10/06
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1867114
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1867114/full
AB  - Background: Pulmonary arterial hypertension (PAH) involves vascular remodeling and altered mechanical signaling. The immune-associated transcriptomic changes accompanying this environment remain incompletely characterized.  Methods: We integrated bulk lung (GSE15197), PBMC (GSE33463), and single-cell RNA-seq (GSE169471) data using a curated set of 2, 537 mechanical-related genes. WGCNA, LASSO, random forest, and single-cell localization supported candidate prioritization. The four-gene panel was examined in a monocrotaline-induced PH rat model and PBMCs from 10 IPAH patients and 10 controls.  Results: PAH transcriptomes showed enrichment of stress-fiber, actomyosin, ECM, and immune-related programs. CD83, CD86, IL6, and TLR7 were prioritized, with compartment-dependent expression patterns. Single-cell data localized CD83/CD86 to myeloid/APC compartments and IL6 to endothelial/fibroblast populations; TLR7 was sparsely detected. In MCT-treated rat lungs, CD86 and TLR7 proteins increased, whereas CD83 and IL-6 decreased. Clinical PBMCs showed corresponding expression directions, and each gene had an AUC >0.7. The exploratory four-gene disease-state score achieved an internal cross-validated AUC of 0.765.  Conclusions: The four candidates provide a cellular and molecular context for investigating immune-stromal interactions in PAH, including responses to noninfectious vascular injury. The panel showed moderate internal discrimination. These findings support further clinical and functional investigation but do not establish direct mechanotransduction targets or a causal pathway linking mechanical stress to vascular inflammation.
SN  - 1664-3224
ER  -