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Record W4386475104 · doi:10.1038/s41467-023-41174-0

Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains

2023· article· en· W4386475104 on OpenAlexafffund
Harold P. Hodgins, Pengsheng Chen, Briallen Lobb, Xin Wei, Benjamin J.-M. Tremblay, Michael J. Mansfield, Victoria C. Y. Lee, Pyung‐Gang Lee, Jeffrey Coffin, Ana T. Duggan, Alexis E. Dolphin, Gabriel Renaud, Min Dong, Andrew C. Doxey

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiphtheria, Corynebacterium, and Tetanus
Canadian institutionsMcMaster UniversityUniversity of Waterloo
FundersNational Institute of Neurological Disorders and StrokeAlliance de recherche numérique du CanadaUniversity of WaterlooNatural Sciences and Engineering Research Council of CanadaOkinawa Institute of Science and Technology Graduate UniversityNational Institutes of HealthGovernment of CanadaJapan Society for the Promotion of ScienceGovernment of OntarioNovo Nordisk FondenCompute Canada
KeywordsClostridium tetaniAncient DNAMetagenomicsPhylogenetic treeBiologyGenomeCladeEvolutionary biologyGeneticsGeneVirologyTetanusVaccinationMedicine

Abstract

fetched live from OpenAlex

The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.926
Threshold uncertainty score0.417

Codex and Gemma teacher scores by category

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

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 head0.022
GPT teacher head0.284
Teacher spread0.262 · 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 teacher head, 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

Citations16
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicDiphtheria, Corynebacterium, and TetanusFrench-language works237,207