ArticleEBioMedicine2024
Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2).BMJ (Clinical research ed.) · 2025Trial
- Whole-Blood Gene Expression and Hypoxic-Ischemic Encephalopathy at Birth.JAMA network open · 2026Article
- Neonatal Bloodstream Infections: A Narrative Review on Diagnostic and Therapeutic Challenges and Prospects in Developing Countries.Health science reports · 2026Article
- Antimicrobial stewardship in UK special care baby units: gaps in research and future directions.JAC-antimicrobial resistance · 2026Review
- Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis.The Journal of infectious diseases · 2026Article
- Systems biology approaches to unravelling neonatal sepsis and potential for precision diagnostics and therapeutics.Frontiers in pharmacology · 2026Review
- Artificial intelligence in pediatric healthcare: bridging potential, clinical practice, and ethical considerations.Clinical and experimental pediatrics · 2025Article
- Article
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Authors and funding
25 authors.
Funding
Abstract
backgroundNeonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation.
methodsAmong 720 initially healthy full-term neonates in two hospitals (The Gambia, West Africa), we identified 21 newborns who were later hospitalized for sepsis in the first 28 days of life, split into early-onset sepsis (EOS, onset ≤7 days of life) and late-onset sepsis (LOS, onset 8-28 days of life), 12 neonates later hospitalized for localized infection without evidence of systemic involvement, and 33 matched control neonates who remained healthy. RNA-seq was performed on peripheral blood collected at birth when all neonates were healthy and also within the first week of life to identify differentially expressed genes (DEGs). Machine learning methods (sPLS-DA, LASSO) identified genes expressed at birth that predicted onset of neonatal sepsis at a later time.
findingsNeonates who later developed EOS already had ∼1000 DEGs at birth when compared to control neonates or those who later developed a localized infection or LOS. Based on these DEGs, a 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) for predicting EOS at birth was developed (training AUC = 0.94, sensitivity = 0.93, specificity = 0.92) and validated in an external cohort (validation AUC = 0.72, sensitivity = 0.83, and specificity = 0.83). Additionally, during the first week of life, EOS disrupted expression of >1800 genes including those influencing immune and metabolic transitions observed in healthy controls.
interpretationDespite appearing healthy at birth, neonates who later developed EOS already had distinct whole blood gene expression changes at birth, which enabled the development of a 4-gene predictive signature for EOS. This could facilitate early recognition and treatment of neonatal sepsis, potentially mitigating its long-term sequelae.
fundingCIHR and NIH/NIAID.
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