Stratification of amyotrophic lateral sclerosis patients: a crowdsourcing approach
Robert Kueffner(Icahn School of Medicine at Mount Sinai), Neta Zach(Teva Pharmaceuticals (Israel)), Maya Bronfeld(University of Haifa), Raquel Norel(IBM (United States)), Nazem Atassi(Massachusetts General Hospital), Venkatachalapathy S. K. Balagurusamy(IBM (United States)), Barbara Di Camillo(University of Padua), Adriano Chiò(University of Turin), Merit Cudkowicz(Massachusetts General Hospital), Donna Dillenberger(IBM (United States)), Javier Garcı́a-Garcı́a(Universitat Pompeu Fabra), Orla Hardiman(Trinity College Dublin), Bruce Hoff(Sage Bionetworks), Joshua Knight(IBM (United States)), Melanie Leitner(BioVentures (United States)), Guang Li(Amazon (United States)), Lara M. Mangravite(Sage Bionetworks), Thea Norman(Sage Bionetworks), Liuxia Wang(Zillow Group (United States)), Rached Alkallas(McGill University), Catalina Anghel(Ontario Institute for Cancer Research), Jeanne Avril(École Polytechnique), Jaume Bacardit(Newcastle University), Barbara Balser, John Balser, Yoav Bar-Sinai(Meir Medical Center), Noa Ben-David(Ben-Gurion University of the Negev), Eyal Ben‐Zion(Ben-Gurion University of the Negev), Robin Bliss, Jialu Cai, Anatoly Chernyshev, Jung-Hsien Chiang(National Cheng Kung University), Davide Chicco(Princess Margaret Cancer Centre), Bhavna Ahuja Nicole Corriveau, Junqiang Dai(University of Kansas Medical Center), Yash Deshpande(IIT@MIT), Eve Desplats, Joseph S. Durgin(University of Pennsylvania), Shadrielle M. G. Espiritu(Ontario Institute for Cancer Research), Fan Fan(Ontario Institute for Cancer Research), Philippe Février(Centre de Recherche en Économie et Statistique), Brooke L. Fridley(Moffitt Cancer Center), Adam Godzik(Sanford Burnham Prebys Medical Discovery Institute), Agnieszka Kitlas Golińska(University of Białystok), Jonathan Gordon(University of Cambridge), Stefan Graw(University of Kansas Medical Center), Yuelong Guo(RTI International), Tim Herpelinck(KU Leuven), Julia F. Hopkins(Ontario Institute for Cancer Research), Barbara Huang(Ontario Institute for Cancer Research), Jeremy Jacobsen(University of Colorado Boulder), Samad Jahandideh(Genex Systems (United States)), Jouhyun Jeon(Ontario Institute for Cancer Research), Wenkai Ji(Chinese Academy of Sciences), Kenneth Jung(Stanford University), Alex Karanevich(University of Kansas Medical Center), Devin C. Koestler(University of Kansas Medical Center), Michael J. Kozak(Tel Aviv University), Christoph Kurz(Helmholtz Zentrum München), Christopher M. Lalansingh(Ontario Institute for Cancer Research), Thomas Larrieu(École Polytechnique), Nicola Lazzarini(Newcastle University), Boaz Lerner(Ben-Gurion University of the Negev), Wojciech Lesiński(University of Białystok), Xiaotao Liang(Fudan University), Xihui Lin(Ontario Institute for Cancer Research), Jarrett Lowe, Lester Mackey(Microsoft (United States)), Richard Meier(University of Kansas Medical Center), Wenwen Min(Wuhan University), Krzysztof Mnich(University of Białystok), Violette Nahmias(École Polytechnique), Janelle Noel‐MacDonnell(Children's Mercy Hospital), Adrienne O’Donnell, Susan Paadre, Ji Park(LinkedIn (United States)), Aneta Polewko-Klim(University of Białystok), Rama Raghavan(University of Kansas Medical Center), Witold R. Rudnicki(University of Białystok), Ehsan Saghapour(Isfahan University of Medical Sciences), Jean-Bernard Salomond(Laboratoire d’Analyse et de Mathématiques Appliquées), Kris Sankaran(Stanford University), Dorota H.S. Sendorek(Ontario Institute for Cancer Research), Vatsal Sharan(Stanford University), Yu-Jia Shiah(Ontario Institute for Cancer Research), Jean-Karl Sirois, Dinithi Sumanaweera(University of Moratuwa), Joseph Usset(University of Kansas Medical Center), Yeeleng S. Vang(University of California, Irvine), Celine Vens(KU Leuven), Dave Wadden(University of Washington), David Wang(Ontario Institute for Cancer Research), Wing Chung Wong(City University of Hong Kong), Xiaohui Xie(University of California, Irvine), Zhiqing Xu, Hsih‐Te Yang(National Cheng Kung University), Xiang Yu(University of Pennsylvania), Haichen Zhang(University of Maryland, Baltimore), Li Zhang, Shihua Zhang(Chinese Academy of Sciences), Shanfeng Zhu(Fudan University), Jinfeng Xiao(University of Illinois Urbana-Champaign), Wen-Chieh Fang(National University of Tainan), Jian Peng(University of Illinois Urbana-Champaign), Chen Yang(National University of Tainan), Huan-Jui Chang(Monash University), Gustavo Stolovitzky(IBM (United States))
Cited by 55Open Access
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease where substantial heterogeneity in clinical presentation urgently requires a better stratification of patients for the development of drug trials and clinical care. In this study we explored stratification through a crowdsourcing approach, the DREAM Prize4Life ALS Stratification Challenge. Using data from >10,000 patients from ALS clinical trials and 1479 patients from community-based patient registers, more than 30 teams developed new approaches for machine learning and clustering, outperforming the best current predictions of disease outcome. We propose a new method to integrate and analyze patient clusters across methods, showing a clear pattern of consistent and clinically relevant sub-groups of patients that also enabled the reliable classification of new patients. Our analyses reveal novel insights in ALS and describe for the first time the potential of a crowdsourcing to uncover hidden patient sub-populations, and to accelerate disease understanding and therapeutic development.