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

Gates Open Research

article

James Berkley¹  James M. Njunge¹  Kirkby Tickell⁴  Abdoulaye Hama Diallo⁵  Abu Sadat Mohammad Sayeem Bin Shahid⁶  Amran Gazi⁶  Ali Saleem⁷  Zaubina Kazi⁷  Syed Ali⁷  Caroline Tigoi¹  Ezekiel Mupere⁸  Christina L. Lancioni⁹  Emily Yoshioka⁴  Mohammod Jobayer Chisti⁶  Moses Mburu¹  Moses Ngari¹  Narshion Ngao¹  Bonface Gichuki¹  Elisha Omer¹  Wilson Gumbi¹  Benson Singa^1,10  Robert Bandsma^1,11  Tahmeed Ahmed⁶  Wieger Voskuijl^1,13  Thomas N. Williams²  Alex Macharia²  Johnstone Makale²  Anna Mitchel^1,16  Jessica Williams^1,16  Joe Gogain^1,16  Nebojsa Janjic^1,16  Rupasri Mandal^1,17  David S. Wishart^1,17  Hang Wu^1,18  Lei Xia^1,18  Michael Routledge^1,18  Yun Yun Gong^1,18  Camilo Espinosa^2,20  Nima Aghaeepour^2,20  Jie Liu^2,23  Eric Houpt^2,23  Trevor D. Lawley^2,24  Hilary Browne^2,24  Yan Shao^2,24  Doreen Rwigi^2,25  Kevin Kariuki^2,25  Timothy Kaburu^2,25  Holm H. Uhlig^2,26  Lisa Gartner^2,26  Kelsey Jones^2,28  Albert Koulman^3,30  Judd Walson⁴ 

[1] The Childhood Acute Illness and Nutrition Network;KEMRI-Wellcome Trust Research Programme;Center for Tropical Medicine and Global Health, University of Oxford;Global Health and Epidemiology, University of Washington;Department of Public Health, Faculty of Health Sciences, University of Ouagadougou;Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research;Department of Pediatrics and Child Health, Aga Khan University Hospital;Department of Paediatrics and Child Health, College of Health Sciences, Makerere University;Department of Pediatrics, Oregon Health and Science University;Kenya Medical Research Institute;Centre for Global Child Health, The Hospital for Sick Children;Department of Biomedical Sciences, University of Malawi College of Medicine;Amsterdam UMC location, University of Amsterdam;Amsterdam Centre for Global Child Health & Emma Children’s Hospital;Institute of Global Health Innovation, Department of Surgery and Cancer, Imperial College London;SomaLogic;Department of Biological Sciences, University of Alberta;School of Food Science and Nutrition, University of Leeds;School of Food and Biological Engineering, Jiangsu University;Departments of Anesthesiology, Pain, and Perioperative Medicine, Stanford University School of Medicine;Department of Pediatrics, Stanford University School of Medicine;Department of Biomedical Data Science, Stanford University School of Medicine, Stanford University School of Medicine;Division of Infectious Diseases and International Health, University of Virginia;Wellcome Sanger Institute;The Centre for Microbiology Research, Kenya Medical Research Institute;Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford;Department of Paediatrics and Biomedical Research Centre, University of Oxford;Kennedy Institute of Rheumatology, University of Oxford;Gastroenterology Department, Great Ormond Street Hospital for Children;MRC Epidemiology Unit, University of Cambridge;NIHR BRC Nutritional Biomarker Laboratory, University of Cambridge

关键词: Case-Cohort;    Mortality;    Children;    LMIC;    Omics;    Systems Biology;   

DOI  :  10.12688/gatesopenres.13635.2

学科分类：电子与电气工程

来源: American Journal Of Pharmtech Research

【 摘 要 】

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

【 授权许可】

CC BY