Whole blood mRNA expression profiling of host molecular networks in neonatal sepsis

  • Claire Smith (Creator)
  • Peter Ghazal (Creator)
  • Paul Dickinson (Creator)
  • Marie Craigon (Creator)
  • Thorsten Forster (Hosting Institution)
  • Alan Ross (Creator)



Gene expression data sets used to identify the gene network and pathway biology associated with neonatal sepsis by determining genome-wide alterations in host RNA in infected infants profiled from control and infected human neonates samples.

PMID: 25120092
PMID: 26484146


Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

Data Citation

Smith CL, Dickinson P, Forster T, Craigon M, Ghazal P et al. Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nat Commun 2014 Aug 14;5:4649. PMID: 25120092

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