Machine learning identified novel players in lipid metabolism, endosomal trafficking, and iron metabolism of the ALS spinal cord

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Although genes causing familial cases have been identified, those of sporadic ALS, which occupies the majority of patients, are still elusive. In this study, we adopted machine learning to buil...

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Bibliographic Details
Main Authors: Jack Cheng, Bor-Tsang Wu, Hsin-Ping Liu, Wei-Yong Lin
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-81315-z
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Summary:Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Although genes causing familial cases have been identified, those of sporadic ALS, which occupies the majority of patients, are still elusive. In this study, we adopted machine learning to build binary classifiers based on the New York Genome Center (NYGC) ALS Consortium’s RNA-seq data of the postmortem spinal cord of ALS and non-neurological disease control. The accuracy of the classifiers was greater than 83% and 77% for the training set and the unseen test set, respectively. The classifiers contained 114 genes. Among them, 41 genes have been reported in previous ALS studies, and others are novel in this field. These genes are involved in mitochondrial respiration, lipid metabolism, endosomal trafficking, and iron metabolism, which may promote the progression of ALS pathology.
ISSN:2045-2322