1. Stratification of amyotrophic lateral sclerosis patients: a crowdsourcing approach
- Author
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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, and Stolovitzky, Gustavo
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,ALS ,Neurosciences ,Clinical Trials and Supportive Activities ,Orphan Drug ,Clinical Research ,Brain Disorders ,Neurodegenerative ,Good Health and Well Being ,Algorithms ,Amyotrophic Lateral Sclerosis ,Clinical Trials as Topic ,Cluster Analysis ,Crowdsourcing ,Databases ,Factual ,Humans ,Ireland ,Italy ,Machine Learning ,Organizations ,Nonprofit ,ALS Stratification Consortium - 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.
- Published
- 2019