Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
Scientific Reports , Volume 9
Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identifed using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Infammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artifcial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artifcially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies signifcantly afected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic efects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identifed by GWAS among the best predictors plus additional predictors with lower efects. The robustness and complementarity of the diferent methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
Romagnoni, A., Jegou, S., van Steen, K., Wainrib, G., Hugot, J., & Peyrin-Biroulet, L. (2019). Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data. Scientific Reports, 9. doi:10.1038/s41598-019-46649-z