Paolo Montaldo1,2, Myrsini Kaforou3, Gabriele Pollara4, David Hervás-Marín5, Ines Calabria5, Joaquin Panadero5, Laia Pedrola5, Peter J Lally6, Vânia Oliveira6, Anup Kage7, Gaurav Atreja7, Josephine Mendoza6, Aung Soe8, Santosh Pattnayak8, Seetha Shankaran9, Máximo Vento5, Jethro Herberg3, Sudhin Thayyil6. 1. Centre for Perinatal Neuroscience, Imperial College London, London, United Kingdomp.montaldo@imperial.ac.uk. 2. Neonatal Unit, Università degli Studi della Campania "Luigi Vanvitelli,", Naples, Italyp.montaldo@imperial.ac.uk. 3. Paediatric Infectious Diseases, Imperial College London, London, United Kingdom. 4. Infection and Immunity, University College London, London, United Kingdom. 5. Health Research Institute La Fe, Valencia, Spain. 6. Centre for Perinatal Neuroscience, Imperial College London, London, United Kingdom. 7. Imperial College Healthcare NHS Trust, London, United Kingdom. 8. Medway NHS Foundation Trust, Gillingham, United Kingdom. 9. Neonatal-Perinatal Division, Wayne State University, Detroit, Michigan, USA.
Abstract
BACKGROUND: Variable responses to hypothermic neuroprotection are related to the clinical heterogeneity of encephalopathic babies; hence better disease stratification may facilitate the development of individualized neuroprotective therapies. OBJECTIVES: We examined if whole blood gene expression analysis can identify specific transcriptome profiles in neonatal encephalopathy. MATERIAL AND METHODS: We performed next-generation sequencing on whole blood RNA from 12 babies with neonatal encephalopathy and 6 time-matched healthy term babies. Genes significantly differentially expressed between encephalopathic and control babies were identified. This set of genes was then compared to the host RNA response in septic neonates and subjected to pathway analysis. RESULTS: We identified 950 statistically significant genes discriminating perfectly between healthy controls and neonatal encephalopathy. The major pathways in neonatal encephalopathy were axonal guidance signaling (p = 0.0009), granulocyte adhesion and diapedesis (p = 0.003), IL-12 signaling and production in macrophages (p = 0.003), and hypoxia-inducible factor 1α signaling (p = 0.004). There were only 137 genes in common between neonatal encephalopathy and bacterial sepsis sets. CONCLUSION: Babies with neonatal encephalopathy have striking differences in gene expression profiles compared with healthy control and septic babies. Gene expression profiles may be useful for disease stratification and for developing personalized neuroprotective therapies. The Author(s). Published by S. Karger AG, Basel.
BACKGROUND: Variable responses to hypothermic neuroprotection are related to the clinical heterogeneity of encephalopathic babies; hence better disease stratification may facilitate the development of individualized neuroprotective therapies. OBJECTIVES: We examined if whole blood gene expression analysis can identify specific transcriptome profiles in neonatal encephalopathy. MATERIAL AND METHODS: We performed next-generation sequencing on whole blood RNA from 12 babies with neonatal encephalopathy and 6 time-matched healthy term babies. Genes significantly differentially expressed between encephalopathic and control babies were identified. This set of genes was then compared to the host RNA response in septic neonates and subjected to pathway analysis. RESULTS: We identified 950 statistically significant genes discriminating perfectly between healthy controls and neonatal encephalopathy. The major pathways in neonatal encephalopathy were axonal guidance signaling (p = 0.0009), granulocyte adhesion and diapedesis (p = 0.003), IL-12 signaling and production in macrophages (p = 0.003), and hypoxia-inducible factor 1α signaling (p = 0.004). There were only 137 genes in common between neonatal encephalopathy and bacterial sepsis sets. CONCLUSION: Babies with neonatal encephalopathy have striking differences in gene expression profiles compared with healthy control and septic babies. Gene expression profiles may be useful for disease stratification and for developing personalized neuroprotective therapies. The Author(s). Published by S. Karger AG, Basel.
Authors: Aurelia Lelli; Karen A Nolan; Sara Santambrogio; Ana Filipa Gonçalves; Miriam J Schönenberger; Anna Guinot; Ian J Frew; Hugo H Marti; David Hoogewijs; Roland H Wenger Journal: Hypoxia (Auckl) Date: 2015-10-08
Authors: Claire L Smith; Paul Dickinson; Thorsten Forster; Marie Craigon; Alan Ross; Mizanur R Khondoker; Rebecca France; Alasdair Ivens; David J Lynn; Judith Orme; Allan Jackson; Paul Lacaze; Katie L Flanagan; Benjamin J Stenson; Peter Ghazal Journal: Nat Commun Date: 2014-08-14 Impact factor: 14.919