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Machine learning identifies novel blood protein predictors of penetrating and stricturing complications in newly diagnosed paediatric Crohn's disease
Author(s) -
Ungaro Ryan C.,
Hu Liangyuan,
Ji Jiayi,
Nayar Shikha,
Kugathasan Subra,
Denson Lee A.,
Hyams Jeffrey,
Dubinsky Marla C.,
Sands Bruce E.,
Cho Judy H.
Publication year - 2021
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.16136
Subject(s) - medicine , crohn's disease , cohort , confidence interval , gastroenterology , cohort study , disease , c reactive protein , inflammation
Summary Background There is a need for improved risk stratification in Crohn's disease. Aim To identify novel blood protein biomarkers associated with future Crohn's disease complications Methods We performed a case‐cohort study utilising a paediatric inception cohort, the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's disease (RISK) study. All patients had inflammatory disease (B1) at baseline. Outcomes were development of stricturing (B2) or penetrating (B3) complications. We assayed 92 inflammation‐related proteins in baseline plasma using a proximity extension assay (Olink Proteomics). An ensemble machine learning technique, random survival forests (RSF), selected variables predicting B2 and B3 complications. Selected analytes were compared to clinical variables and serology only models. We examined selected proteins in a single‐cell sequencing cohort to analyse differential cell expression in blood and ileum. Results We included 265 patients with mean age 11.6 years (standard deviation [SD] 3.2). Seventy‐three and 34 patients, respectively, had B2 and B3 complications within mean 1123 (SD 477) days for B2 and 1251 (442) for B3. A model with 5 protein markers predicted B3 complications with an area under the curve (AUC) of 0.79 (95% confidence interval [CI] 0.76‐0.82) compared to 0.69 (95% CI 0.66‐0.72) for serologies and 0.74 (95% CI 0.71‐0.77) for clinical variables. A model with 4 protein markers predicted B2 complications with an AUC of 0.68 (95% CI 0.65‐0.71) compared to 0.62 (95% CI 0.59‐0.65) for serologies and 0.52 (95% CI 0.50‐0.55) for clinical variables. B2 analytes were highly expressed in ileal stromal cells while B3 analytes were prominent in peripheral blood and ileal T cells. Conclusions We identified novel blood proteomic markers, distinct for B2 and B3, associated with progression of paediatric Crohn's disease.