Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

© 2019, The Author(s). Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified 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 Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial 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 artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected 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 effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different 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

Pareto optimal-based feature selection framework for biomarker identification

Numerous computational techniques have been applied to identify the vital features of gene expression datasets in aiming to increase the efficiency of biomedical applications. The classification of microarray data samples is an important task to correctly recognise diseases by identifying small but clinically meaningful genes. However, identification of disease representative genes or biomarkers in high dimensional microarray gene-expression datasets remains a challenging task. This thesis investigates the viability of Pareto optimisation in identifying relevant subsets of biomarkers in high-dimensional microarray datasets. A robust Pareto Optimal based feature selection framework for biomarker discovery is then proposed. First, a two-stage feature selection approach using ensemble filter methods and Pareto Optimality is proposed. The integration of the multi-objective approach employing Pareto Optimality starts with well-known filter methods applied to various microarray gene-expression datasets. Although filter methods provide ranked lists of features, they do not give information about optimum subsets of features, which are namely genes in this study. To address this limitation, the Pareto Optimality is incorporated along with filter methods. The robustness of the proposed framework is successfully demonstrated on several well-known microarray gene expression datasets and it is shown to achieve comparable or up to 100% predictive accuracy with comparatively fewer features. Better performance results are obtained in comparison with other approaches, which are single-objective approaches. Furthermore, cross-validation and k-fold approaches are integrated into the framework, which can enhance the over-fitting problem and the gene selection process is subsequently more accurate under various conditions. Then the proposed framework is developed in several phases. The Sequential Forward Selection method (SFS) is first used to represent wrapper techniques, and the developed Pareto Optimality based framework is applied multiple times and tested on different data types. Given the nature of most real-life data, imbalanced classes are examined using the proposed framework. The classifier achieves high performance at a similar level of different cases using the proposed Pareto Optimal based feature selection framework, which has a novel structure for imbalanced classes. Comparable or better gene subset sizes are obtained using the proposed framework. Finally, handling missing data within the proposed framework is investigated and it is demonstrated that different data imputation methods can also help in the effective integration of various feature selection methods