FAIR SCI Ahead: The Evolution of the Open Data Commons for Pre-Clinical Spinal Cord Injury Research

Fouad, Karim; Bixby, John L.; Callahan, Alison; Grethe, Jeffrey S.; Jakeman, Lyn B.; Lemmon, Vance; Magnuson, David S.K.; Martone, Maryann E.; Nielson, Jessica L.; Schwab, Jan M.; Taylor-Burds, Carol; Tetzlaff, Wolfram; Torres-Espín, Abel; Ferguson, Adam R.; Alam, Sabina; Bacon, M.; Bambrick, Linda L.; Basso, M.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Gensel, John C.; Graham, Dustin M.; Grethe, Jeff S.; Huie, J. Russell; Jones, L. H.; Kabitzke, Patricia; Kleitman, Naomi; Kusiak, Audrey; Kwon, Brian K.; Lederer, Rosi; MacLeod, Malcom; May, Verena E.L.; Neff, Ellen P.; Rabchevsky, Sasha

doi:10.1089/neu.2019.6674

Cited by 28 publications

(17 citation statements)

References 23 publications

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“…However, simple additions to data collection can help gather vital information regarding how sex hormones affect outcomes of biological phenomena and treatment, even if significant effects are underpowered in any given study. The field of SCI has established an open data commons for depositing information from research studies which is being used to mine big-data sets gathered across multiple neurotrauma centers [( 161 , 162 ), ODC-SCI 1 ]. The more data which enters these public domains, the higher probability exists to derive meaningful relationships that may have not been directly evident within the scope of a given study.…”

Section: Resultsmentioning

confidence: 99%

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies.

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Section: Resultsmentioning

confidence: 99%

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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“…There has been limited consideration of the effects of aging on SCI in current SCI research. In contrast to the human SCI population, the majority of preclinical research is performed in young adult rodents (2–4 months), and less than 0.35% of experimental rodents used are 12 months or older (representing 40 years of age in humans) [ 5 ]. This is likely to be a significant impediment to translating preclinical research into viable clinical therapies.…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Sutherland

Sefiani

Horvat

et al. 2021

Cells

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The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

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“…The first case study is used as a tutorial to illustrate the steps of analysis; the second case study is discussed at the end of the results section. For the first case, we used a publicly available preclinical dataset on the Open Data Commons for Spinal Cord Injury ( odc-sci.org ) ( Callahan et al, 2017 ; Fouad et al, 2019 ). We selected a subset of the dataset with accession number ODC-SCI: 26 ( Ferguson et al, 2018 ) that has been previously used for deriving the so-called spinal cord injury (SCI) syndromics ( Ferguson et al, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Reproducible analysis of disease space via principal components using the novel R package syndRomics

Torres-Espín

Chou

Huie

et al. 2021

eLife

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Biomedical data are usually analyzed at the univariate level, focused on a single primary outcome measure to provide insight into systems biology, complex disease states, and precision medicine opportunities. More broadly, these complex biological and disease states can be detected as common factors emerging from the relationships among measured variables using multivariate approaches. ‘Syndromics’ refers to an analytical framework for measuring disease states using principal component analysis and related multivariate statistics as primary tools for extracting underlying disease patterns. A key part of the syndromic workflow is the interpretation, the visualization, and the study of robustness of the main components that characterize the disease space. We present a new software package, syndRomics, an open-source R package with utility for component visualization, interpretation, and stability for syndromic analysis. We document the implementation of syndRomics and illustrate the use of the package in case studies of neurological trauma data.

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FAIR SCI Ahead: The Evolution of the Open Data Commons for Pre-Clinical Spinal Cord Injury Research

Cited by 28 publications

References 23 publications

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Reproducible analysis of disease space via principal components using the novel R package syndRomics

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