The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia

• DOI: 10.12688/gatesopenres.13635.2
• Publication Date: 2022-11-03T09:35:58Z
• Authors: James M. Njunge; Kirkby Tickell; Abdoulaye Hama Di...; Abu Sadat Mohamma...; Md. Amran Gazi; Ali Saleem; Zaubina Kazi; Syed Ali; Caroline Tigoi; Ezekiel Mupere; Christina L. Lanc...; Emily Yoshioka; Mohammod Jobayer ...; Moses Mburu; Moses Ngari; Narshion Ngao; Bonface Gichuki; Elisha Omer; Wilson Gumbi; Benson Singa; Robert Bandsma; Tahmeed Ahmed; Wieger Voskuijl; Thomas N. Williams; Alex Macharia; Johnstone Makale; Anna Mitchel; Jessica Williams; Joe Gogain; Nebojsa Janjic; Rupasri Mandal; David S. Wishart; Hang Wu; Lei Xia; Michael Routledge; Yun Yun Gong; Camilo Espinosa; Nima Aghaeepour; Jie Liu; Eric Houpt; Trevor D. Lawley; Hilary Browne; Yan Shao; Doreen Rwigi; Kevin Kariuki; Timothy Kaburu; Holm H. Uhlig; Lisa Gartner; Kelsey Jones; Albert Koulman; Judd Walson; James Berkley
• Keywords: Omics

<ns4:p><ns4:bold>Introduction</ns4:bold>: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning may suggest optimal pathways to target for interventions further reduce mortality. The Childhood Acute Illness Nutrition (CHAIN) Network (<ns4:ext-link xmlns:ns5="http://www.w3.org/1999/xlink" ext-link-type="uri" ns5:href="http://www.chainnnetwork.org">www.chainnnetwork.org</ns4:ext-link>) Nested Case-Cohort Study (CNCC) aims investigate leading inpatient post-discharge through an integrated multi-omic approach.</ns4:p><ns4:p> <ns4:bold>Methods analysis</ns4:bold>; CNCC comprises subset participants from CHAIN cohort (1278/3101 hospitalised participants, including 350 who died 658 survivors, 270/1140 well community similar age household location) nine sites six countries across sub-Saharan Africa South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome biomarkers enteropathy will be determined. Computational systems biology analysis include machine learning multivariate predictive modelling with stacked generalization approaches accounting different characteristics each modality. This approach is anticipated yield mechanistic insights, show interactions behaviours components entities, help develop among children.</ns4:p><ns4:p> <ns4:bold>Ethics dissemination</ns4:bold>. was approved by institutional review boards all partner sites. Results published open access, peer reviewed scientific journals presented academic policy stakeholders. Data made publicly available, uploading recognised omics databases.</ns4:p><ns4:p> <ns4:bold>Trial registration</ns4:bold> NCT03208725.</ns4:p>