Elevated expression of B4GALT6, GABRA1, GAD2, GLRA3, HTR2A, PCSK1, and SLC17A6 are postmortem markers for the ALS-Ox subtype
Eshima, J.; Pennington, T. R.; Choudhury, R.; Garcia, J. M.; Fricks, J.; Smith, B. S.
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In this work, we stratify 428 bulk RNA-seq spinal cord transcriptomes from 206 ALS patients to assess concordance with cortical phenotype. We find the postmortem spinal cord generally recaptures the molecular phenotypes observed in the postmortem cortex and observe weaker differences in patient survival after correction for repeat measures. We compare intra-patient subtype assigned in the cortex and spinal cord, finding modest agreement between the cortex and lumbar region specifically, ranging from 46.2 - 66.7%. We leverage differential expression analysis to identify seven marker genes for the oxidative stress (ALS-Ox) subtype that show consistent upregulation in both the cortex and spinal cord and utilize three to construct classifiers that achieve notable predictive power for the ALS-Ox subtype in three different holdout cohorts, with AUCs ranging from 0.81 - 0.89. Our study shows the ALS-Ox subtype is conserved in the spinal cord of the same patients, offering a postmortem foundation for clinical stratification.
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