IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0059712.html
   My bibliography  Save this article

Derivation of Multivariate Syndromic Outcome Metrics for Consistent Testing across Multiple Models of Cervical Spinal Cord Injury in Rats

Author

Listed:
  • Adam R Ferguson
  • Karen-Amanda Irvine
  • John C Gensel
  • Jessica L Nielson
  • Amity Lin
  • Johnathan Ly
  • Mark R Segal
  • Rajiv R Ratan
  • Jacqueline C Bresnahan
  • Michael S Beattie

Abstract

Spinal cord injury (SCI) and other neurological disorders involve complex biological and functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental models represents a significant challenge for translating findings across research projects and presents a substantial hurdle for translation of novel therapies to humans. In the present work we demonstrate a novel ‘syndromic’ information-processing approach for capitalizing on heterogeneous data from diverse preclinical models of SCI to discover translational outcomes for therapeutic testing. We first built a large, detailed repository of preclinical outcome data from 10 years of basic research on cervical SCI in rats, and then applied multivariate pattern detection techniques to extract features that are conserved across different injury models. We then applied this translational knowledge to derive a data-driven multivariate metric that provides a common ‘ruler’ for comparisons of outcomes across different types of injury (NYU/MASCIS weight drop injuries, Infinite Horizons (IH) injuries, and hemisection injuries). The findings revealed that each individual endpoint provides a different view of the SCI syndrome, and that considering any single outcome measure in isolation provides a misleading, incomplete view of the SCI syndrome. This limitation was overcome by taking a novel multivariate integrative approach for leveraging complex data from preclinical models of neurological disease to identify therapies that target multiple outcomes. We suggest that applying this syndromic approach provides a roadmap for translating therapies for SCI and other complex neurological diseases.

Suggested Citation

  • Adam R Ferguson & Karen-Amanda Irvine & John C Gensel & Jessica L Nielson & Amity Lin & Johnathan Ly & Mark R Segal & Rajiv R Ratan & Jacqueline C Bresnahan & Michael S Beattie, 2013. "Derivation of Multivariate Syndromic Outcome Metrics for Consistent Testing across Multiple Models of Cervical Spinal Cord Injury in Rats," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-13, March.
  • Handle: RePEc:plo:pone00:0059712
    DOI: 10.1371/journal.pone.0059712
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059712
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0059712&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0059712?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. H Bart van der Worp & David W Howells & Emily S Sena & Michelle J Porritt & Sarah Rewell & Victoria O'Collins & Malcolm R Macleod, 2010. "Can Animal Models of Disease Reliably Inform Human Studies?," PLOS Medicine, Public Library of Science, vol. 7(3), pages 1-8, March.
    2. Bruce Korth & L.R Tucker, 1976. "Procrustes matching by congruence coefficients," Psychometrika, Springer;The Psychometric Society, vol. 41(4), pages 531-535, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hristo Todorov & Emily Searle-White & Susanne Gerber, 2020. "Applying univariate vs. multivariate statistics to investigate therapeutic efficacy in (pre)clinical trials: A Monte Carlo simulation study on the example of a controlled preclinical neurotrauma trial," PLOS ONE, Public Library of Science, vol. 15(3), pages 1-20, March.
    2. Rebecca A Nishi & Anna Badner & Mitra J Hooshmand & Dana A Creasman & Hongli Liu & Aileen J Anderson, 2020. "The effects of mouse strain and age on a model of unilateral cervical contusion spinal cord injury," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-19, June.

    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. Lauralyn A McIntyre & David Moher & Dean A Fergusson & Katrina J Sullivan & Shirley H J Mei & Manoj Lalu & John Marshall & Malcolm Mcleod & Gilly Griffin & Jeremy Grimshaw & Alexis Turgeon & Marc T Av, 2016. "Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-16, January.
    2. Kimberley E Wever & Carlijn R Hooijmans & Niels P Riksen & Thomas B Sterenborg & Emily S Sena & Merel Ritskes-Hoitinga & Michiel C Warlé, 2015. "Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-17, November.
    3. Robyn M. Lucas & Rachael M. Rodney Harris, 2018. "On the Nature of Evidence and ‘Proving’ Causality: Smoking and Lung Cancer vs. Sun Exposure, Vitamin D and Multiple Sclerosis," IJERPH, MDPI, vol. 15(8), pages 1-13, August.
    4. Nathalie Percie du Sert & Viki Hurst & Amrita Ahluwalia & Sabina Alam & Marc T Avey & Monya Baker & William J Browne & Alejandra Clark & Innes C Cuthill & Ulrich Dirnagl & Michael Emerson & Paul Garne, 2020. "The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research," PLOS Biology, Public Library of Science, vol. 18(7), pages 1-12, July.
    5. Bossert, Leonie & Hagendorff, Thilo, 2021. "Animals and AI. The role of animals in AI research and application – An overview and ethical evaluation," Technology in Society, Elsevier, vol. 67(C).
    6. Constance Holman & Sophie K Piper & Ulrike Grittner & Andreas Antonios Diamantaras & Jonathan Kimmelman & Bob Siegerink & Ulrich Dirnagl, 2016. "Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke," PLOS Biology, Public Library of Science, vol. 14(1), pages 1-12, January.
    7. Robin van Eenige & Peternella S Verhave & Peter J Koemans & Ivo A C W Tiebosch & Patrick C N Rensen & Sander Kooijman, 2020. "RandoMice, a novel, user-friendly randomization tool in animal research," PLOS ONE, Public Library of Science, vol. 15(8), pages 1-8, August.
    8. Petr Květon & Martin Jelínek & Iva Burešová, 2022. "Psychometric Properties of the Sport Multidimensional Perfectionism Scale-2 in Czech Adolescent Athletes: An Exploratory Approach," SAGE Open, , vol. 12(3), pages 21582440221, July.
    9. Henk Kiers & Patrick Groenen, 1996. "A monotonically convergent algorithm for orthogonal congruence rotation," Psychometrika, Springer;The Psychometric Society, vol. 61(2), pages 375-389, June.
    10. Susanne Wieschowski & Diego S Silva & Daniel Strech, 2016. "Animal Study Registries: Results from a Stakeholder Analysis on Potential Strengths, Weaknesses, Facilitators, and Barriers," PLOS Biology, Public Library of Science, vol. 14(11), pages 1-12, November.
    11. Konstantinos K Tsilidis & Orestis A Panagiotou & Emily S Sena & Eleni Aretouli & Evangelos Evangelou & David W Howells & Rustam Al-Shahi Salman & Malcolm R Macleod & John P A Ioannidis, 2013. "Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases," PLOS Biology, Public Library of Science, vol. 11(7), pages 1-10, July.
    12. Carol Kilkenny & William J Browne & Innes C Cuthill & Michael Emerson & Douglas G Altman, 2010. "Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research," PLOS Biology, Public Library of Science, vol. 8(6), pages 1-5, June.
    13. David Krauth & Andrew Anglemyer & Rose Philipps & Lisa Bero, 2014. "Nonindustry-Sponsored Preclinical Studies on Statins Yield Greater Efficacy Estimates Than Industry-Sponsored Studies: A Meta-Analysis," PLOS Biology, Public Library of Science, vol. 12(1), pages 1-10, January.
    14. Philippa M Bennett & Sarah K Stewart & Janine Dretzke & Danai Bem & Jowan G Penn-Barwell, 2018. "Preclinical therapies to prevent or treat fracture non-union: A systematic review," PLOS ONE, Public Library of Science, vol. 13(8), pages 1-22, August.
    15. Julie E. Goodman & Catherine Petito Boyce & Sonja N. Sax & Leslie A. Beyer & Robyn L. Prueitt, 2015. "Rethinking Meta‐Analysis: Applications for Air Pollution Data and Beyond," Risk Analysis, John Wiley & Sons, vol. 35(6), pages 1017-1039, June.
    16. Urbano Lorenzo-Seva & Antoni Rodríguez-Fornells, 2006. "Acquiescent Responding in Balanced Multidimensional Scales and Exploratory Factor Analysis," Psychometrika, Springer;The Psychometric Society, vol. 71(4), pages 769-777, 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:plo:pone00:0059712. 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: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    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.