University of Sheffield | June 2018 | Children’s immune system could hold the key to preventing sepsis
An international team of scientists, including academics from the University of Sheffield and the public health graduate school at Harvard University, have studied children and adults with sepsis or blood poisoning. Their analysis and comparison of child and adult blood profiles showed that children are naturally more resistant to lots of infectious diseases. Importantly, this analysis enabled the research team to identify key differences in cell-pathway activity in the blood of septic adults and children.
Winston Hide, Professor of Computational Biology at Sheffield’s Institute of Translational Neuroscience (SITraN), said:
“During outbreaks like Spanish flu and Ebola we know that children survived much better than adults. By analysing the blood profiles of infected children and comparing them to adults with sepsis we were able to identify children whose natural resilience helped them to ward off infection (Source: University of Sheffield).
The study which is the first-of-its-kind has now been published in the journal Molecular Systems Biology where it may be read or downloaded
Attempts to develop drugs that address sepsis based on leads developed in animal models have failed. We sought to identify leads based on human data by exploiting a natural experiment: the relative resistance of children to mortality from severe infections and sepsis. Using public datasets, we identified key differences in pathway activity (Pathprint) in blood transcriptome profiles of septic adults and children. To find drugs that could promote beneficial (child) pathways or inhibit harmful (adult) ones, we built an in silico pathway drug network (PDN) using expression correlation between drug, disease, and pathway gene signatures across 58,475 microarrays. Specific pathway clusters from children or adults were assessed for correlation with drug‐based signatures. Validation by literature curation and by direct testing in an endotoxemia model of murine sepsis of the most correlated drug candidates demonstrated that the Pathprint‐PDN methodology is more effective at generating positive drug leads than gene‐level methods (e.g., CMap). Pathway‐centric Pathprint‐PDN is a powerful new way to identify drug candidates for intervention against sepsis and provides direct insight into pathways that may determine survival.
Full reference: |The relative resistance of children to sepsis mortality: from pathways to drug candidates |Molecular Systems Biology| DOI 10.15252/msb.20177998