Evidence map›Paper›PMID 41928087›Full record

ArticleMolecular medicine (Cambridge, Mass.)2026

Pathway-level profiling of the sepsis proteome reveals immune and transcriptional dysregulation.

Logan R Van Nynatten, David Tweddell, Mark Daley, Gediminas Cepinskas, John Basmaji, Marat Slessarev, Douglas D Fraser

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PubMed Full text at PMC Publisher
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Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

2 citing papers in PubMed.

  1. 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

7 authors.

Logan R Van NynattenCritical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. Logan.VanNynatten@lhsc.on.ca.
David TweddellComputer Science, Western University, London, ON, Canada.
Mark DaleyComputer Science, Western University, London, ON, Canada.
Gediminas CepinskasMedical Biophysics, Western University, London, ON, Canada.
John BasmajiCritical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Marat SlessarevCritical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Douglas D FraserPhysiology and Pharmacology, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSepsis triggers a complex and heterogeneous host response, yet decades of biomarker studies have yielded few targeted therapeutics that improve patient outcomes. Single analyte approaches fail to capture the coordinated biological programs that drive organ dysfunction. Focusing on single or limited panels of biomarkers to endotype disease fundamentally misrepresents sepsis biology, which reflects simultaneous disruption of multiple cellular networks. However, pathway-level bioinformatic analyses interpret proteins as components of larger biological systems, enabling detection of coordinated molecular disturbances that individual biomarkers cannot capture.

methodsWe conducted an exploratory cohort study profiling 1,196 plasma proteins in 15 critically-ill adults with sepsis on ICU Day 1 and Day 3 using proximity extension assays. Differential expression, Reactome and Gene Ontology (GO) enrichment analyses, protein-protein interaction networks, and immune cell deconvolution were combined to assess pathway-level perturbations and their clinical correlates.

resultsEarly sepsis was defined by widespread inflammatory pathway dysregulation, with marked enrichment of immune system activation, neutrophil degranulation, cytokine signaling, and defense-response pathways. Despite significant clinical improvement of patients between ICU Day 1 and Day 3, only five proteins (ALDH3A1, CR2, CD200R1, IL1RL2, SAA4) demonstrated temporal change. Moreover, transcriptional pathways demonstrated negative enrichment by Day 3. Network analyses revealed highly interconnected inflammatory hubs centered on IL-6, IL-10, and CXCL8.

conclusionsIn this exploratory cohort, early sepsis was characterized by enrichment of immune and transcriptional pathways. These pathway signals were consistently detected across multiple analytic approaches, including differential expression analysis, pathway enrichment, and protein-protein interaction network analyses. These findings highlight the value of high-dimensional, pathway-focused proteomic analyses for uncovering the biological programs underlying critical illness beyond what can be captured by individual biomarkers.

Indexed as

Gene Expression RegulationProteomeProteomicsSepsisAgedBiomarkersBlood ProteinsComputational BiologyFemaleGene Expression ProfilingHumansMaleMiddle AgedProtein Interaction MapsSignal TransductionBiomarkersBlood ProteinsProteomeBioinformaticsBiomarkersCritical careEnrichmentPathway biologyProteomicsSepsis

Identifiers

PMID41928087
PMCPMC13169637

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.