- Kueffner, Robert;
- Zach, Neta;
- Bronfeld, Maya;
- Norel, Raquel;
- Atassi, Nazem;
- Balagurusamy, Venkat;
- Di Camillo, Barbara;
- Chio, Adriano;
- Cudkowicz, Merit;
- Dillenberger, Donna;
- Garcia-Garcia, Javier;
- Hardiman, Orla;
- Hoff, Bruce;
- Knight, Joshua;
- Leitner, Melanie L;
- Li, Guang;
- Mangravite, Lara;
- Norman, Thea;
- Wang, Liuxia;
- Xiao, Jinfeng;
- Fang, Wen-Chieh;
- Peng, Jian;
- Yang, Chen;
- Chang, Huan-Jui;
- Stolovitzky, Gustavo
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.