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Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis
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  • Published: 03 February 2026

Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis

  • Kairui Yang1 na1,
  • Yunlong Hu2 na1,
  • Chunhui Ma1,
  • Jianing Wang2,
  • Yang Wang1,
  • Xuejie Han1,
  • Jiafeng Lv1,
  • Xiaolei Zhang3 &
  • …
  • Yunliang Cui1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Computational biology and bioinformatics
  • Diseases
  • Immunology

Abstract

Sepsis is an infection-induced systemic inflammatory response syndrome. T cell remodeling and senescence are linked to sepsis, so identifying T cell-related genes (TCRGs) and senescence-related genes (SRGs) as biomarkers is crucial for elucidating mechanisms, diagnosis, and targeted therapy. TCRGs were derived from single-cell sequencing data. Biomarkers were screened via differential expression analysis, machine learning, and expression analysis of public transcriptome data. Molecular mechanisms were explored through artificial neural network (ANN), GSEA, immune infiltration analysis, and drug prediction, with RT-qPCR validation in clinical samples. PATZ1, SIN3B, BLK, and MTHFD2 were identified. MTHFD2 was upregulated in sepsis, while the other three were downregulated (P < 0.001); MTHFD2 showed no significant difference in validation (P > 0.05). The ANN had high prediction accuracy. These genes were enriched in phosphatidylinositol signaling, hematopoietic cell lineage, and DNA replication. Immune infiltration analysis revealed correlations between the biomarkers and immune cells (e.g., PATZ1 with CD8 T cells/neutrophils). Emetine, latamoxef, and dihydroergotamine bound stably to the biomarkers. PATZ1, SIN3B, BLK, and MTHFD2, as T cell and senescence-related biomarkers in sepsis, offered valuable insights into sepsis pathogenesis and targeted therapy.

Data availability

The datasets (GSE154918, GSE28750, and GSE175453) supporting the conclusions of this article is(are) available in the [GEO] repository, [https://www.ncbi.nlm.nih.gov/gds]. The raw data and analysis code generated in this study have been deposited in the figshare repository and are accessible via the identifier [https://doi.org/10.6084/m9.figshare.30925289].

Abbreviations

TCRGs:

T cell-related genes

SRGs:

Senescence-related genes

T cells:

T lymphocytes

PPI:

Protein–protein interaction

nFeature_RNA:

Gene count per cell

nCount_RNA:

Aggregate RNA molecule number

percent.mt:

Mitochondrial transcript percentage

MSigDB:

Molecular signatures database

cDNA:

Complementary DNA

NK:

Natural killer

CMP:

Common myeloid progenitors

BP:

Biological processes

CC:

Cellular component

MF:

Molecular function

SIN3B:

SIN3 transcription regulator family member B

BLK:

B lymphoid kinase

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

SSc:

Systemic sclerosis

HF:

Halofuginone

RA:

Rheumatoid arthritis

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Acknowledgements

We would like to express our sincere gratitude to all individuals and organizations who supported and assisted us throughout this research. Special thanks to the following people: Shuliu Zhang, Weiwei Li, and Ruirui Liu. In conclusion, we extend our thanks to everyone who has supported and assisted us along the way. Without your support, this research would not have been possible. The research reported in this project was generously supported by Shandong Provincial Medical and Health Science and Technology Development Program Project under grant agreement number 202117011071, and Jinan Municipal Clinical Medical Science and Technology Innovation Program Project under grant agreement number 20213406.

Funding

The research reported in this project was generously supported by Shandong Provincial Medical and Health Science and Technology Development Program Project (Grant number 202117011071) and Jinan Municipal Clinical Medical Science and Technology Innovation Program Project (Grant number 202134069). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Kairui Yang and Yunlong Hu.

Authors and Affiliations

  1. Department of Intensive Care Unit, The 960Th Hospital of The PLA Joint Logistic Support Force, Jinan, Shandong, China

    Kairui Yang, Chunhui Ma, Yang Wang, Xuejie Han, Jiafeng Lv & Yunliang Cui

  2. Department of Emergency and Intensive Care Unit, The 966th Hospital of The PLA Joint Logistic Support Force, Dandong, Liaoning, China

    Yunlong Hu & Jianing Wang

  3. The Health Unit of the 32128 Unit of the Chinese People’s Liberation Army, Beijing, China

    Xiaolei Zhang

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  1. Kairui Yang
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Contributions

KY, YH and YC contributed to study conception and design. KY, YH, CM, JW, YW, XH, JL and XZ contributed to data extraction, data interpretation, data analysis, data presentation and manuscript preparation. KY, YH and YC wrote the manuscript. All authors participated in manuscript preparation, and data review.

Corresponding author

Correspondence to Yunliang Cui.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the 960th Hospital of the PLA Joint Logistic Support Force located in Jinan. The approval number and date of approval are as follows: No. 2021-44 and March 5, 2021.

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All patients provided written informed consent at the time of clinical sample collection for experiments, ensuring that the research process complied with ethical norms and that patients’ rights and wishes were fully respected.

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Yang, K., Hu, Y., Ma, C. et al. Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38559-8

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  • Received: 12 December 2025

  • Accepted: 29 January 2026

  • Published: 03 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-38559-8

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Keywords

  • Sepsis
  • T cell
  • Senescence
  • Transcriptome sequencing analysis
  • Biomarkers
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