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Record W3171360477 · doi:10.1016/j.mcpro.2021.100096

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury

2021· article· en· W3171360477 on OpenAlexafffund
Michael A. Skinnider, Jason C. Rogalski, Seth Tigchelaar, Neda Manouchehri, Anna Prudova, Angela Jackson, Karina Nielsen, Jaihyun Jeong, Shalini Chaudhary, Katelyn Shortt, Ylonna Gallagher-Kurtzke, Kitty So, Allan Fong, Rishab Gupta, Elena B. Okon, Michael A. Rizzuto, Kevin Dong, Femke Streijger, Lise Bélanger, Leanna Ritchie, Angela Tsang, Sean Christie, Jean‐Marc Mac‐Thiong, Christopher S. Bailey, Tamir Ailon, Raphaële Charest-Morin, Nicolas Dea, Jefferson R. Wilson, Sanjay S. Dhall, Scott Paquette, John Street, Charles G. Fisher, Marcel F. Dvorak, Casey P. Shannon, Christoph H. Borchers, Robert Balshaw, Leonard J. Foster, Brian K. Kwon

Bibliographic record

VenueMolecular & Cellular Proteomics · 2021
Typearticle
Languageen
FieldMedicine
TopicSpinal Cord Injury Research
Canadian institutionsPrevention of Organ FailureUniversity of VictoriaUniversité de MontréalLondon Health Sciences CentreCentre Hospitalier Universitaire Sainte-JustineDalhousie UniversityUniversity of British ColumbiaInternational Collaboration On Repair DiscoveriesSt. Michael's HospitalCanada's Michael Smith Genome Sciences CentreUniversity of TorontoWestern UniversityHôpital du Sacré-Cœur de MontréalVancouver Spine Surgery Institute
FundersUniversity of British ColumbiaGenome British ColumbiaMichael Smith Health Research BCWestern Canada Research GridRick Hansen InstituteFondation Brain CanadaVGH and UBC Hospital FoundationCompute CanadaCanadian Institutes of Health ResearchGenome CanadaWings for Life
KeywordsSpinal cord injuryMedicineCerebrospinal fluidGlial fibrillary acidic proteinSpinal cordClinical trialBiomarkerNeuroscienceBioinformaticsBiologyPathology

Abstract

fetched live from OpenAlex

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.035
GPT teacher head0.337
Teacher spread0.302 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations29
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueMolecular & Cellular ProteomicsSame topicSpinal Cord Injury ResearchFrench-language works237,207