TY - JOUR
T1 - Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning
AU - Din Abdul Jabbar, Muzammil Arif
AU - Guo, Ling
AU - Nag, Sonakshi
AU - Guo, Yang
AU - Simmons, Zachary
AU - Pioro, Erik P.
AU - Ramasamy, Savitha
AU - Yeo, Crystal Jing Jing
N1 - Publisher Copyright:
© 2023 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.
PY - 2024
Y1 - 2024
N2 - Objective: To predict ALS progression with varying observation and prediction window lengths, using machine learning (ML). Methods: We used demographic, clinical, and laboratory parameters from 5030 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to model ALS disease progression as fast (at least 1.5 points decline in ALS Functional Rating Scale-Revised (ALSFRS-R) per month) or non-fast, using Extreme Gradient Boosting (XGBoost) and Bayesian Long Short Term Memory (BLSTM). XGBoost identified predictors of progression while BLSTM provided a confidence level for each prediction. Results: ML models achieved area under receiver-operating-characteristics curve (AUROC) of 0.570-0.748 and were non-inferior to clinician assessments. Performance was similar with observation lengths of a single visit, 3, 6, or 12 months and on a holdout validation dataset, but was better for longer prediction lengths. 21 important predictors were identified, with the top 3 being days since disease onset, past ALSFRS-R and forced vital capacity. Nonstandard predictors included phosphorus, chloride and albumin. BLSTM demonstrated higher performance for the samples about which it was most confident. Patient screening by models may reduce hypothetical Phase II/III clinical trial sizes by 18.3%. Conclusion: Similar accuracies across ML models using different observation lengths suggest that a clinical trial observation period could be shortened to a single visit and clinical trial sizes reduced. Confidence levels provided by BLSTM gave additional information on the trustworthiness of predictions, which could aid decision-making. The identified predictors of ALS progression are potential biomarkers and therapeutic targets for further research.
AB - Objective: To predict ALS progression with varying observation and prediction window lengths, using machine learning (ML). Methods: We used demographic, clinical, and laboratory parameters from 5030 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to model ALS disease progression as fast (at least 1.5 points decline in ALS Functional Rating Scale-Revised (ALSFRS-R) per month) or non-fast, using Extreme Gradient Boosting (XGBoost) and Bayesian Long Short Term Memory (BLSTM). XGBoost identified predictors of progression while BLSTM provided a confidence level for each prediction. Results: ML models achieved area under receiver-operating-characteristics curve (AUROC) of 0.570-0.748 and were non-inferior to clinician assessments. Performance was similar with observation lengths of a single visit, 3, 6, or 12 months and on a holdout validation dataset, but was better for longer prediction lengths. 21 important predictors were identified, with the top 3 being days since disease onset, past ALSFRS-R and forced vital capacity. Nonstandard predictors included phosphorus, chloride and albumin. BLSTM demonstrated higher performance for the samples about which it was most confident. Patient screening by models may reduce hypothetical Phase II/III clinical trial sizes by 18.3%. Conclusion: Similar accuracies across ML models using different observation lengths suggest that a clinical trial observation period could be shortened to a single visit and clinical trial sizes reduced. Confidence levels provided by BLSTM gave additional information on the trustworthiness of predictions, which could aid decision-making. The identified predictors of ALS progression are potential biomarkers and therapeutic targets for further research.
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U2 - 10.1080/21678421.2023.2285443
DO - 10.1080/21678421.2023.2285443
M3 - Article
C2 - 38052485
AN - SCOPUS:85179677567
SN - 2167-8421
VL - 25
SP - 242
EP - 255
JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
IS - 3-4
ER -