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Molecular subtypes of ALS are associated with differences in patient prognosis

Author

Listed:
  • Jarrett Eshima

    (Arizona State University)

  • Samantha A. O’Connor

    (Arizona State University)

  • Ethan Marschall

    (Arizona State University)

  • Robert Bowser

    (Barrow Neurological Institute
    Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center)

  • Christopher L. Plaisier

    (Arizona State University)

  • Barbara S. Smith

    (Arizona State University)

Abstract

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.

Suggested Citation

  • Jarrett Eshima & Samantha A. O’Connor & Ethan Marschall & Robert Bowser & Christopher L. Plaisier & Barbara S. Smith, 2023. "Molecular subtypes of ALS are associated with differences in patient prognosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35494-w
    DOI: 10.1038/s41467-022-35494-w
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    References listed on IDEAS

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    1. Daniel D. Lee & H. Sebastian Seung, 1999. "Learning the parts of objects by non-negative matrix factorization," Nature, Nature, vol. 401(6755), pages 788-791, October.
    2. X. Rosa Ma & Mercedes Prudencio & Yuka Koike & Sarat C. Vatsavayai & Garam Kim & Fred Harbinski & Adam Briner & Caitlin M. Rodriguez & Caiwei Guo & Tetsuya Akiyama & H. Broder Schmidt & Beryl B. Cummi, 2022. "TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A," Nature, Nature, vol. 603(7899), pages 124-130, March.
    3. Anna-Leigh Brown & Oscar G. Wilkins & Matthew J. Keuss & Sarah E. Hill & Matteo Zanovello & Weaverly Colleen Lee & Alexander Bampton & Flora C. Y. Lee & Laura Masino & Yue A. Qi & Sam Bryce-Smith & Ar, 2022. "TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A," Nature, Nature, vol. 603(7899), pages 131-137, March.
    4. Shane A. Liddelow & Kevin A. Guttenplan & Laura E. Clarke & Frederick C. Bennett & Christopher J. Bohlen & Lucas Schirmer & Mariko L. Bennett & Alexandra E. Münch & Won-Suk Chung & Todd C. Peterson & , 2017. "Neurotoxic reactive astrocytes are induced by activated microglia," Nature, Nature, vol. 541(7638), pages 481-487, January.
    5. Mahtab Tavasoli & Sarah Lahire & Stanislav Sokolenko & Robyn Novorolsky & Sarah Anne Reid & Abir Lefsay & Meredith O. C. Otley & Kitipong Uaesoontrachoon & Joyce Rowsell & Sadish Srinivassane & Molly , 2022. "Mechanism of action and therapeutic route for a muscular dystrophy caused by a genetic defect in lipid metabolism," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
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