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Record W3082470015 · doi:10.1101/2020.08.29.273326

Epigenetic inheritance and the evolution of infectious diseases

2020· preprint· en· W3082470015 on OpenAlexafffund
David V. McLeod, Geoff Wild, Francisco Úbeda

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsWestern University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsVirulenceEpigeneticsBiologyNatural selectionGeneticsMeaslesGeneDNA methylationVirologySelection (genetic algorithm)Gene expressionVaccination

Abstract

fetched live from OpenAlex

Abstract Genes with identical DNA sequences may show differential expression because of epigenetic marks. These marks in pathogens are key to their virulence and are being evaluated as targets for medical treatment. Where epigenetic marks were created in response to past conditions (epigenetically inherited), they represent a form of memory, the impact of which has not been considered in the evolution of infectious diseases. We fill this gap by exploring the evolution of virulence in pathogens that inherit epigenetic information on the sex of their previous host. We show that memories of past hosts can also provide clues about the sex of present and future hosts when women and men differ in their immunity to infection and/or their interactions with the sexes. These biological and social differences between the sexes are pervasive in humans. We show that natural selection can favour the evolution of greater virulence in infections originating from one sex. Furthermore, natural selection can favour the evolution of greater virulence in infections across sexes (or within sexes). Our results explain certain patterns of virulence in diseases like measles, chickenpox and polio that have puzzled medical researchers for decades. In particular, they address why girls infected by boys (or boys infected by girls) are more likely to die from the infection than girls infected by girls (or boys infected by boys). We propose epigenetic therapies to treat infections by tampering with the memories of infecting pathogens. Counterintuitively, we predict that successful therapies should target pathogen’s genes that inhibit virulence, rather than those enhancing virulence. Our findings imply that pathogens can carry memories of past environments other than sex (e.g. those related to socioeconomic status) that may condition their virulence and could signify an important new direction in personalised medicine.

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)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.010
GPT teacher head0.216
Teacher spread0.207 · 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 designTheoretical or conceptual
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

Citations0
Published2020
Admission routes2
Has abstractyes

Explore more

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