Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
Authors: Romagnoni Alberto , Jégou Simon , Van Steen Kristel , Wainrib Gilles , Hugot Jean-Pierre ,   International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Peyrin-Biroulet Laurent , Chamaillard Mathias , Colombel Jean-Frederick , Cottone Mario , D’Amato Mauro , D’Incà Renata , Halfvarson Jonas , Henderson Paul , Karban Amir , Kennedy Nicholas A. , Khan Mohammed Azam , Lémann Marc , Levine Arie , Massey Dunecan , Milla Monica , Ng Sok Meng Evelyn , Oikonomou Ioannis , Peeters Harald , Proctor Deborah D. , Rahier Jean-Francois , Rutgeerts Paul , Seibold Frank , Stronati Laura , Taylor Kirstin M. , Törkvist Leif , Ublick Kullak , Van Limbergen Johan , Van Gossum Andre , Vatn Morten H. , Zhang Hu , Zhang Wei , Andrews Jane M. , Bampton Peter A. , Barclay Murray , Florin Timothy H. , Gearry Richard , Krishnaprasad Krupa , Lawrance Ian C. , Mahy Gillian , Montgomery Grant W. , Radford-Smith Graham , Roberts Rebecca L. , Simms Lisa A. , Hanigan Katherine , Croft Anthony , Amininijad Leila , Cleynen Isabelle , Dewit Olivier , Franchimont Denis , Georges Michel , Laukens Debby , Peeters Harald , Rahier Jean-Francois , Rutgeerts Paul , Theatre Emilie , Van Gossum André , Vermeire Severine , Aumais Guy , Baidoo Leonard , Barrie Arthur M. , Beck Karen , Bernard Edmond-Jean , Binion David G. , Bitton Alain , Brant Steve R. , Cho Judy H. , Cohen Albert , Croitoru Kenneth , Daly Mark J. , Datta Lisa W. , Deslandres Colette , Duerr Richard H. , Dutridge Debra , Ferguson John , Fultz Joann , Goyette Philippe , Greenberg Gordon R. , Haritunians Talin , Jobin Gilles , Katz Seymour , Lahaie Raymond G. , McGovern Dermot P. , Nelson Linda , Ng Sok Meng , Ning Kaida , Oikonomou Ioannis , Paré Pierre , Proctor Deborah D. , Regueiro Miguel D. , Rioux John D. , Ruggiero Elizabeth , Schumm L. Philip , Schwartz Marc , Scott Regan , Sharma Yashoda , Silverberg Mark S. , Spears Denise , Steinhart A. Hillary , Stempak Joanne M. , Swoger Jason M. , Tsagarelis Constantina , Zhang Wei , Zhang Clarence , Zhao Hongyu , Aerts Jan , Ahmad Tariq , Arbury Hazel , Attwood Anthony , Auton Adam , Ball Stephen G. , Balmforth Anthony J. , Barnes Chris , Barrett Jeffrey C. , Barroso Inês , Barton Anne , Bennett Amanda J. , Bhaskar Sanjeev , Blaszczyk Katarzyna , Bowes John , Brand Oliver J. , Braund Peter S. , Bredin Francesca , Breen Gerome , Brown Morris J. , Bruce Ian N. , Bull Jaswinder , Burren Oliver S. , Burton John , Byrnes Jake , Caesar Sian , Cardin Niall , Clee Chris M. , Coffey Alison J. , MC Connell John , Conrad Donald F. , Cooper Jason D. , Dominiczak Anna F. , Downes Kate , Drummond Hazel E. , Dudakia Darshna , Dunham Andrew , Ebbs Bernadette , Eccles Diana , Edkins Sarah , Edwards Cathryn , Elliot Anna , Emery Paul , Evans David M. , Evans Gareth , Eyre Steve , Farmer Anne , Ferrier I. Nicol , Flynn Edward , Forbes Alistair , Forty Liz , Franklyn Jayne A. , Frayling Timothy M. , Freathy Rachel M. , Giannoulatou Eleni , Gibbs Polly , Gilbert Paul , Gordon-Smith Katherine , Gray Emma , Green Elaine , Groves Chris J. , Grozeva Detelina , Gwilliam Rhian , Hall Anita , Hammond Naomi , Hardy Matt , Harrison Pile , Hassanali Neelam , Hebaishi Husam , Hines Sarah , Hinks Anne , Hitman Graham A. , Hocking Lynne , Holmes Chris , Howard Eleanor , Howard Philip , Howson Joanna M. M. , Hughes Debbie , Hunt Sarah , Isaacs John D. , Jain Mahim , Jewell Derek P. , Johnson Toby , Jolley Jennifer D. , Jones Ian R. , Jones Lisa A. , Kirov George , Langford Cordelia F. , Lango-Allen Hana , Lathrop G. Mark , Lee James , Lee Kate L. , Lees Charlie , Lewis Kevin , Lindgren Cecilia M. , Maisuria-Armer Meeta , Maller Julian , Mansfield John , Marchini Jonathan L. , Martin Paul , Massey Dunecan CO , McArdle Wendy L. , McGuffin Peter , McLay Kirsten E. , McVean Gil , Mentzer Alex , Mimmack Michael L. , Morgan Ann E. , Morris Andrew P. , Mowat Craig , Munroe Patricia B. , Myers Simon , Newman William , Nimmo Elaine R. , O’Donovan Michael C. , Onipinla Abiodun , Ovington Nigel R. , Owen Michael J. , Palin Kimmo , Palotie Aarno , Parnell Kirstie , Pearson Richard , Pernet David , Perry John RB , Phillips Anne , Plagnol Vincent , Prescott Natalie J. , Prokopenko Inga , Quail Michael A. , Rafelt Suzanne , Rayner Nigel W. , Reid David M. , Renwick Anthony , Ring Susan M. , Robertson Neil , Robson Samuel , Russell Ellie , Clair David St , Sambrook Jennifer G. , Sanderson Jeremy D. , Sawcer Stephen J. , Schuilenburg Helen , Scott Carol E. , Scott Richard , Seal Sheila , Shaw-Hawkins Sue , Shields Beverley M. , Simmonds Matthew J. , Smyth Debbie J. , Somaskantharajah Elilan , Spanova Katarina , Steer Sophia , Stephens Jonathan , Stevens Helen E. , Stirrups Kathy , Stone Millicent A. , Strachan David P. , Su Zhan , Symmons Deborah P. M. , Thompson John R. , Thomson Wendy , Tobin Martin D. , Travers Mary E. , Turnbull Clare , Vukcevic Damjan , Wain Louise V. , Walker Mark , Walker Neil M. , Wallace Chris , Warren-Perry Margaret , Watkins Nicholas A. , Webster John , Weedon Michael N. , Wilson Anthony G. , Woodburn Matthew , Wordsworth B. Paul , Yau Chris , Young Allan H. , Zeggini Eleftheria , Brown Matthew A. , Burton Paul R. , Caulfield Mark J. , Compston Alastair , Farrall Martin , Gough Stephen C. L. , Hall Alistair S. , Hattersley Andrew T. , Hill Adrian V. S. , Mathew Christopher G. , Pembrey Marcus , Satsangi Jack , Stratton Michael R. , Worthington Jane , Hurles Matthew E. , Duncanson Audrey , Ouwehand Willem H. , Parkes Miles , Rahman Nazneen , Todd John A. , Samani Nilesh J. , Kwiatkowski Dominic P. , McCarthy Mark I. , Craddock Nick , Deloukas Panos , Donnelly Peter , Blackwell Jenefer M. , Bramon Elvira , Casas Juan P. , Corvin Aiden , Jankowski Janusz , Markus Hugh S. , Palmer Colin NA , Plomin Robert , Rautanen Anna , Trembath Richard C. , Viswanathan Ananth C. , Wood Nicholas W. , Spencer Chris C. A. , Band Gavin , Bellenguez Céline , Freeman Colin , Hellenthal Garrett , Giannoulatou Eleni , Pirinen Matti , Pearson Richard , Strange Amy , Blackburn Hannah , Bumpstead Suzannah J. , Dronov Serge , Gillman Matthew , Jayakumar Alagurevathi , McCann Owen T. , Liddle Jennifer , Potter Simon C. , Ravindrarajah Radhi , Ricketts Michelle , Waller Matthew , Weston Paul , Widaa Sara , Whittaker Pamela 
Published: July 2019

AbstractCrohn 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.