Genetic Mechanisms of Amyotrophic Lateral Sclerosis Based on Whole-Genome Sequencing

This study investigated the genetic mechanisms of amyotrophic lateral sclerosis based on whole-genome sequencing data, employing a secondary mining strategy on host whole-genome sequencing data to systematically characterize the oral microbiome community structure and functional reprogramming patterns in ALS patients. A total of 99 participants were enrolled, including 28 sporadic ALS patients, 24 biological parental controls, and 47 healthy controls. A two-stage alignment strategy was implemented to strictly remove host background sequences, followed by taxonomic profiling using MetaPhlAn4 and functional pathway annotation using HUMAnN3. The study revealed a unique "alpha-stability and beta-reorganization" ecological pattern in the oral microbiome of ALS patients, with 8 core microbial biomarkers consistently identified across dual-control comparisons. A random forest classification model constructed based on these biomarkers demonstrated good discriminative performance with a mean AUC of 0.766 in 10-fold cross-validation. Functional analysis identified significant enrichment of the ABC transporters pathway, providing novel insights into microbiome-host interactions in ALS pathogenesis.