Identifying patterns in amyotrophic lateral sclerosis progression from sparse longitudinal data
Authors: Ramamoorthy Divya , Severson Kristen , Ghosh Soumya , Sachs Karen ,   Answer ALS, Baxi Emily G. , Coyne Alyssa N. , Mosmiller Elizabeth , Hayes Lindsey , Cerezo Aianna , Ahmad Omar , Roy Promit , Zeiler Steven , Krakauer John W. , Li Jonathan , Donde Aneesh , Huynh Nhan , Adam Miriam , Wassie Brook T. , Lenail Alex , Patel-Murray Natasha Leanna , Raghav Yogindra , Sachs Karen , Kozareva Velina , Tsitkov Stanislav , Ehrenberger Tobias , Kaye Julia A. , Lima Leandro , Wyman Stacia , Vertudes Edward , Amirani Naufa , Raja Krishna , Thomas Reuben , Lim Ryan G. , Miramontes Ricardo , Wu Jie , Vaibhav Vineet , Matlock Andrea , Venkatraman Vidya , Holewenski Ronald , Sundararaman Niveda , Pandey Rakhi , Manalo Danica-Mae , Frank Aaron , Ornelas Loren , Panther Lindsey , Gomez Emilda , Galvez Erick , Perez Daniel , Meepe Imara , Lei Susan , Pinedo Louis , Liu Chunyan , Moran Ruby , Sareen Dhruv , Landin Barry , Agurto Carla , Cecchi Guillermo , Norel Raquel , Thrower Sara , Luppino Sarah , Farrar Alanna , Pothier Lindsay , Yu Hong , Sinani Ervin , Vigneswaran Prasha , Sherman Alexander V. , Farr S. Michelle , Mandefro Berhan , Trost Hannah , Banuelos Maria G. , Garcia Veronica , Workman Michael , Ho Richie , Baloh Robert , Roggenbuck Jennifer , Harms Matthew B. , Prina Carolyn , Heintzman Sarah , Kolb Stephen , Stocksdale Jennifer , Wang Keona , Morgan Todd , Heitzman Daragh , Jamil Arish , Jockel-Balsarotti Jennifer , Karanja Elizabeth , Markway Jesse , McCallum Molly , Miller Tim , Joslin Ben , Alibazoglu Deniz , Ajroud-Driss Senda , Beavers Jay C. , Bellard Mary , Bruce Elizabeth , Maragakis Nicholas , Cudkowicz Merit E. , Berry James , Thompson Terri , Finkbeiner Steven , Thompson Leslie M. , Van Eyk Jennifer E. , Svendsen Clive N. , Rothstein Jeffrey D. , Glass Jonathan D. , Fournier Christina N. ,   Pooled Resource Open-Access ALS Clinical Trials Consortium, Sherman Alexander ,   ALS/MND Natural History Consortium, Lunetta Christian , Walk David , Hayat Ghazala , Wymer James , Gwathmey Kelly , Olney Nicholas , Ajroud-Driss Senda , Heiman-Patterson Terry , Arcila-Londono Ximena , Faulconer Kenneth , Sanani Ervin , Berger Alex , Mirochnick Julia , Herrington Todd M. , Berry James D. , Ng Kenney , Fraenkel Ernest 
Published: September 2022

AbstractThe clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought to determine whether there were common patterns of disease progression that could aid in the design and analysis of clinical trials. We developed an approach based on a mixture of Gaussian processes to identify clusters of patients sharing similar disease progression patterns, modeling their average trajectories and the variability in each cluster. We show that ALS progression is frequently nonlinear, with periods of stable disease preceded or followed by rapid decline. We also show that our approach can be extended to Alzheimer’s and Parkinson’s diseases. Our results advance the characterization of disease progression of ALS and provide a flexible modeling approach that can be applied to other progressive diseases.