{
  "abstract": "Sepsis is heterogeneous, and transcripts that distinguish sepsis from health may lack clinical specificity. We tested whether S100A8 is reproducibly associated with sepsis and maps to a donor-aware myeloid state defined independently of S100A8. A discovery whole-blood cohort was analyzed on the log2 robust multi-array average scale using maximum-probe aggregation, limma, weighted gene co-expression network analysis (WGCNA), and leakage-controlled feature prioritization. The analysis identified 1,508 differentially expressed genes; 265 overlapped the strongest sepsis-positive WGCNA module. The network retained all 802 samples and 11,719 genes; the black-module eigengene correlated with sepsis status (r = 0.409; false-discovery rate 3.72 × 10 − 33), and S100A8 belonged to this module (module membership 0.700). S100A8 was upregulated (log2 fold change 1.87; false-discovery rate 2.15 × 10 − 171). Discrimination against clinical comparators was contrast dependent, and outcome analyses did not support a stable prognostic association. Donor-level monocyte pseudo-bulk analysis supported increased S100A8 and decreased HLA-DRA but included only two control and four sepsis donors. Across single-cell datasets, S100A8 tracked an emergency-myeloid program and inversely tracked antigen presentation. In THP-1 cells, S100A8 knockdown attenuated lipopolysaccharide-associated reductions in CD74 and HLA-DRα. Triptolide retained a similar NF-κB phosphorylation effect after S100A8 knockdown, providing no evidence that this effect required S100A8. S100A8 is therefore prioritized as a marker of a sepsis-associated emergency-myeloid, HLA-DR-low state, not as an established diagnostic, prognostic, direct drug-binding, or therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "The Second Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.",
    "Bengbu Medical University, Bengbu, Anhui, China.",
    "Anhui Provincial Key Laboratory of Infection and Immunity, Bengbu Medical University, Bengbu, Anhui, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Changlong Zhang",
      "orcid": "0009-0005-2624-1165"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Qianqian Cui"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qiyun Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wei Tang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lei Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Liang Chu",
      "orcid": "0000-0002-8257-7326"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6445neszbh3x7.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359578",
  "fulltext_url": "https://europepmc.org/articles/PMC13686462",
  "id": "6445neszbh3x7",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359578",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ],
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      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNA"
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      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors"
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    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Monocytes"
    ],
    [
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      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Monocytes"
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      "/Biology and life sciences/Computational biology/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Monocytes"
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    ],
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      "plos",
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    ],
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      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Sepsis"
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      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Monocytes"
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      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
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      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxic agents/Toxins/Bacterial toxins/Endotoxins"
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  "pdf_url": "https://europepmc.org/articles/PMC13686462?pdf=render",
  "pmcid": "PMC13686462",
  "pmid": "42905799",
  "published": "2026-10-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/6445neszbh3x7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pone.0359578",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359578"
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    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42905799",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42905799"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
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  ],
  "title": "Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis",
  "title_text": "Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/6445neszbh3x7",
  "venue": "PLOS One",
  "versions": []
}