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Unsupervised Phenotypic Clustering for Determining Clinical Status in Children with Cystic Fibrosis

Filipow, N; Davies, G; Main, E; Sebire, NJ; Wallis, C; Ratjen, F; Stanojevic, S; (2021) Unsupervised Phenotypic Clustering for Determining Clinical Status in Children with Cystic Fibrosis. European Respiratory Journal 10.1183/13993003.02881-2020. (In press).

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Abstract

BACKGROUND: Cystic Fibrosis (CF) is a multisystem disease in which assessing disease severity based on lung function alone may not be appropriate. The aim of the study was to develop a comprehensive machine-learning algorithm to assess clinical status independent of lung function in children. METHODS: A comprehensive prospectively collected clinical database (Toronto, Canada) was used to apply unsupervised cluster analysis. The defined clusters were then compared by current and future lung function, risk of future hospitalisation, and risk of future pulmonary exacerbation (PEx) treated with oral antibiotics. A K-Nearest Neighbours (KNN) algorithm was used to prospectively assign clusters. The methods were validated in a paediatric clinical CF dataset from Great Ormond Street Hospital (GOSH). RESULTS: The optimal cluster model identified four (A-D) phenotypic clusters based on 12 200 encounters from 530 individuals. Two clusters (A,B) consistent with mild disease were identified with high FEV1, and low risk of both hospitalisation and PEx treated with oral antibiotics. Two clusters (C,D) consistent with severe disease were also identified with low FEV1. Cluster D had the shortest time to both hospitalisation and PEx treated with oral antibiotics. The outcomes were consistent in 3124 encounters from 171 children at GOSH. The KNN cluster allocation error rate was low, at 2.5% (Toronto), and 3.5% (GOSH). CONCLUSION: Machine learning derived phenotypic clusters can predict disease severity independent of lung function and could be used in conjunction with functional measures to predict future disease trajectories in CF patients.

Type: Article
Title: Unsupervised Phenotypic Clustering for Determining Clinical Status in Children with Cystic Fibrosis
Location: England
DOI: 10.1183/13993003.02881-2020
Publisher version: http://dx.doi.org/10.1183/13993003.02881-2020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10120037
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