IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-022-35494-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35494-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35494-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. 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.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Rebecca San Gil & Dana Pascovici & Juliana Venturato & Heledd Brown-Wright & Prachi Mehta & Lidia Madrid San Martin & Jemma Wu & Wei Luan & Yi Kit Chui & Adekunle T. Bademosi & Shilpa Swaminathan & Se, 2024. "A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Salim Megat & Natalia Mora & Jason Sanogo & Olga Roman & Alberto Catanese & Najwa Ouali Alami & Axel Freischmidt & Xhuljana Mingaj & Hortense Calbiac & François Muratet & Sylvie Dirrig-Grosch & Stépha, 2023. "Integrative genetic analysis illuminates ALS heritability and identifies risk genes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Hannah E. Salapa & Patricia A. Thibault & Cole D. Libner & Yulian Ding & Joseph-Patrick W. E. Clarke & Connor Denomy & Catherine Hutchinson & Hashim M. Abidullah & S. Austin Hammond & Landon Pastushok, 2024. "hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS)," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Yufeng Liang & Sydney Willey & Yu-Chieh Chung & Yi-Meng Lo & Shiqin Miao & Sarah Rundell & Li-Chun Tu & Dennis Bong, 2023. "Intracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Del Corso, Gianna M. & Romani, Francesco, 2019. "Adaptive nonnegative matrix factorization and measure comparisons for recommender systems," Applied Mathematics and Computation, Elsevier, vol. 354(C), pages 164-179.
    6. P Fogel & C Geissler & P Cotte & G Luta, 2022. "Applying separative non-negative matrix factorization to extra-financial data," Working Papers hal-03689774, HAL.
    7. Xiao-Bai Li & Jialun Qin, 2017. "Anonymizing and Sharing Medical Text Records," Information Systems Research, INFORMS, vol. 28(2), pages 332-352, June.
    8. Naiyang Guan & Lei Wei & Zhigang Luo & Dacheng Tao, 2013. "Limited-Memory Fast Gradient Descent Method for Graph Regularized Nonnegative Matrix Factorization," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-10, October.
    9. Spelta, A. & Pecora, N. & Rovira Kaltwasser, P., 2019. "Identifying Systemically Important Banks: A temporal approach for macroprudential policies," Journal of Policy Modeling, Elsevier, vol. 41(1), pages 197-218.
    10. M. Moghadam & K. Aminian & M. Asghari & M. Parnianpour, 2013. "How well do the muscular synergies extracted via non-negative matrix factorisation explain the variation of torque at shoulder joint?," Computer Methods in Biomechanics and Biomedical Engineering, Taylor & Francis Journals, vol. 16(3), pages 291-301.
    11. Markovsky, Ivan & Niranjan, Mahesan, 2010. "Approximate low-rank factorization with structured factors," Computational Statistics & Data Analysis, Elsevier, vol. 54(12), pages 3411-3420, December.
    12. Paul Fogel & Yann Gaston-Mathé & Douglas Hawkins & Fajwel Fogel & George Luta & S. Stanley Young, 2016. "Applications of a Novel Clustering Approach Using Non-Negative Matrix Factorization to Environmental Research in Public Health," IJERPH, MDPI, vol. 13(5), pages 1-14, May.
    13. Le Thi Khanh Hien & Duy Nhat Phan & Nicolas Gillis, 2022. "Inertial alternating direction method of multipliers for non-convex non-smooth optimization," Computational Optimization and Applications, Springer, vol. 83(1), pages 247-285, September.
    14. Chae, Bongsug (Kevin), 2018. "The Internet of Things (IoT): A Survey of Topics and Trends using Twitter Data and Topic Modeling," 22nd ITS Biennial Conference, Seoul 2018. Beyond the boundaries: Challenges for business, policy and society 190376, International Telecommunications Society (ITS).
    15. Jingfeng Guo & Chao Zheng & Shanshan Li & Yutong Jia & Bin Liu, 2022. "BiInfGCN: Bilateral Information Augmentation of Graph Convolutional Networks for Recommendation," Mathematics, MDPI, vol. 10(17), pages 1-16, August.
    16. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    17. Jianfei Cao & Han Yang & Jianshu Lv & Quanyuan Wu & Baolei Zhang, 2023. "Estimating Soil Salinity with Different Levels of Vegetation Cover by Using Hyperspectral and Non-Negative Matrix Factorization Algorithm," IJERPH, MDPI, vol. 20(4), pages 1-15, February.
    18. Amina Zahaf & Abdelmoumen Kassoussi & Tom Hutteau-Hamel & Amine Mellouk & Corentine Marie & Lida Zoupi & Foteini Tsouki & Claudia Mattern & Pierre Bobé & Michael Schumacher & Anna Williams & Carlos Pa, 2023. "Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    19. Wang, Ketong & Porter, Michael D., 2018. "Optimal Bayesian clustering using non-negative matrix factorization," Computational Statistics & Data Analysis, Elsevier, vol. 128(C), pages 395-411.
    20. Semi Min & Juyong Park, 2019. "Modeling narrative structure and dynamics with networks, sentiment analysis, and topic modeling," PLOS ONE, Public Library of Science, vol. 14(12), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35494-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.