Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning

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Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning
Title:
Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning
Journal Title:
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Publication Date:
06 December 2023
Citation:
Din Abdul Jabbar, M. A., Guo, L., Nag, S., Guo, Y., Simmons, Z., Pioro, E. P., Ramasamy, S., & Yeo, C. J. J. (2023). Predicting amyotrophic lateral sclerosis (ALS) progression with machine learning. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 1–14. https://doi.org/10.1080/21678421.2023.2285443
Abstract:
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.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
There was no specific funding for the research done
Description:
This is an Accepted Manuscript of an article published by Taylor & Francis in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration on 6 December 2023, available online: http://www.tandfonline.com/doi.org/10.1080/21678421.2023.2285443
ISSN:
2167-9223
2167-8421
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