TY - JOUR
T1 - Molecular subtypes of ALS are associated with differences in patient prognosis
AU - NYGC ALS Consortium
AU - Eshima, Jarrett
AU - O’Connor, Samantha A.
AU - Marschall, Ethan
AU - Bowser, Robert
AU - Plaisier, Christopher L.
AU - Smith, Barbara
N1 - Funding Information:
The authors would like to acknowledge The Target ALS Human Postmortem Tissue Core, New York Genome Center for Genomics of Neurogenerative Disease, Amyotrophic Lateral Sclerosis Association, Tow Foundation, and the patients and family members for supporting this analysis. The authors would like to acknowledge Solo Pyon for his assistance with the high-speed download of patient sequencing data from the European Bioinformatics Institute data repository (NCBI mirror). The authors thank Paula Phan for her assistance with vector-based figure preparation. The authors would like to thank Oliver. H Tam and Molly G. Hammell for their correspondence regarding unsupervised clustering. The authors would also like to thank Yu-Jui Ho for his assistance with SAKE usage and installation. All NYGC ALS Consortium activities are supported by the ALS Association (ALSA, 19-SI-459) and the Tow Foundation. J.E. is supported by the National Science Foundation, Graduate Research Fellowship (026257-001).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.
AB - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.
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U2 - 10.1038/s41467-022-35494-w
DO - 10.1038/s41467-022-35494-w
M3 - Article
C2 - 36609402
AN - SCOPUS:85145870335
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 95
ER -