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.
James M NjungeKirkby TickellAbdoulaye Hama DialloAbu Sadat Mohammad Sayeem Bin ShahidMd Amran GaziAli SaleemZaubina KaziSyed AliCaroline TigoiEzekiel MupereChristina L LancioniEmily YoshiokaMohammod Jobayer ChistiMoses MburuMoses NgariNarshion NgaoBonface M GichukiElisha OmerWilson GumbiBenson O SingaRobert BandsmaTahmeed AhmedWieger VoskuijlThomas N WilliamsAlex MachariaJohnstone MakaleAnna MitchelJessica WilliamsJoe GogainNebojsa JanjicRupasri MandalDavid S WishartHang WuLei XiaMichael RoutledgeYun Yun GongCamilo EspinosaNima AghaeepourJie LiuEric R HouptTrevor D LawleyHilary BrowneYan ShaoDoreen RwigiKevin KariukiTimothy KaburuHolm H UhligLisa GartnerKelsey JonesAlbert KoulmanJudd L WalsonJames BerkleyPublished in: Gates open research (2022)
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.
Keyphrases
- cardiovascular events
- young adults
- physical activity
- machine learning
- healthcare
- risk factors
- liver failure
- randomized controlled trial
- clinical trial
- systematic review
- single cell
- minimally invasive
- type diabetes
- drug induced
- pain management
- respiratory failure
- data analysis
- dna methylation
- intensive care unit
- copy number
- study protocol
- electronic health record
- multidrug resistant
- quality improvement
- hiv infected
- mechanical ventilation
- extracorporeal membrane oxygenation
- network analysis
- global health