{
  "abstract": "BackgroundWhole-blood host-response signatures can distinguish infection-positive from infection-negative systemic inflammation, but their signal combines changes in leucocyte composition with regulation within cells. We asked whether a retrospectively selected and subsequently fixed blood transcriptomic framework could relate candidate transcripts to granulocyte-associated and monocyte/macrophage-associated expression contexts rather than serve as another stand-alone diagnostic product.MethodsA 12-gene framework was retrospectively derived from four contrasts across three studies (444 contrast-level observations; 443 unique arrays) and subsequently fixed for external evaluation using a single-sample transcriptome-rank score. Performance was examined separately across cohorts with different specimens, age groups and comparators. Transcript-score sensitivity analyses, donor-level whole-blood single-cell pseudobulk and cell-line qRT-PCR were used to assess candidate localization and cell-line expression-context concordance. Cis-eQTL Mendelian randomisation and colocalisation were included as exploratory genetic context.ResultsIn the closest target-context cohort, GSE134347, the fixed score achieved an AUROC of 0.827 (95% CI 0.764–0.889) for sepsis versus non-infectious critical illness. Performance was lower in pediatric day-1 SIRS comparisons, indicating dependence on population and comparator context. Adjustment for alternative neutrophil-associated transcript scores produced a marker-dependent ordering, with SMPDL3A among the most attenuated and PLA2G7 among the least attenuated candidates; no candidate remained FDR-significant in the primary six-gene family. Donor-level single-cell analysis and qRT-PCR supported a monocyte/macrophage context for PLA2G7 and granulocyte-like localization of the diagnostic immune markers. Exploratory Mendelian randomisation did not support a susceptibility effect for the testable immunometabolism-associated candidates, and the HLA-DRB1 regional signal lacked evidence of a shared variant under single-variant colocalisation assumptions.ConclusionThis study provides an auditable, cell-informed framework that relates granulocyte-associated transcription to PLA2G7-associated monocyte/macrophage localization within the whole-blood infection response. The framework is intended for biological prioritisation, and it defines testable candidates for future studies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Yaodong Gu"
    },
    {
      "name": "Yue Yu"
    },
    {
      "name": "Wenrui Zhang"
    },
    {
      "name": "Wenbo Liu"
    },
    {
      "name": "Cuiping Zhao"
    },
    {
      "name": "Shizhen Ding"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6twegqatem8qv.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1958259",
  "fulltext_url": null,
  "id": "6twegqatem8qv",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958259",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6twegqatem8qv.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T06:20:16Z",
      "native_id": "10.3389/fimmu.2026.1958259",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958259"
    },
    {
      "first_seen": "2026-11-03T12:21:20Z",
      "native_id": "10.3389/fimmu.2026.1958259",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958259/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Cell-informed host-response profiling distinguishes neutrophil-like and PLA2G7-associated immunometabolic axes in systemic infection",
  "title_text": "Cell-informed host-response profiling distinguishes neutrophil-like and PLA2G7-associated immunometabolic axes in systemic infection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:02Z",
  "url": "https://research.draconitic.com/paper/6twegqatem8qv",
  "venue": "Frontiers in Immunology",
  "versions": []
}