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Record W4411390332 · doi:10.1101/2025.06.16.659550

Biosynthesis of glycosylated 5-hydroxycytosine in the DNA of diverse viruses

2025· preprint· en· W4411390332 on OpenAlexaff
Yan‐Jiun Lee, Jianjun Li, Cecilia Sobieski, Jacek Stupak, Evgeny Vinogradov, Hongyan Zhou, Wangxue Chen, Peter Weigele, Danielle L. Peters

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldEnvironmental Science
TopicBacteriophages and microbial interactions
Canadian institutionsBrock UniversityNational Research Council Canada
Fundersnot available
KeywordsComputational biologyDNABiosynthesisBiologyVirologyGeneticsGene

Abstract

fetched live from OpenAlex

Characterizing viral strategies for circumventing cellular defenses is critical to understanding the biology and therapeutic application of bacteriophages as antimicrobials. Many bacteriophages synthesize complex modifications (i.e. hypermodifications) to the nucleobases of their virion DNA in order to circumvent the endonuclease-based defenses of their hosts. To date, most hypermodified pyrimidines in viruses are synthesized via group transfer to a pre-existing hydroxyl moiety in DNA during the later stages of lytic development leading up to packaging of the viral chromosome into the capsid. Typically, these occur at hydroxymethylcytosine or hydroxymethyluracil. We find mono- and poly-arabinosylated cytidines completely replacing canonical cytidine in the native DNA of the Escherichia phage RB69 and Acinetobacter baumannii phage DLP3. In both cases, an arabinosyl moiety is connected directly to the pyrimidine through an ether linkage, with the bridging oxygen originating from 5-hydroxycytosine (5hoC) in DNA. The 5hoC is synthesized as a mononucleotide by a virally encoded thymidylate synthase homolog. We find diverse virally encoded thymidylate synthase homologs, including the Rhizobium phage RL38J1, are capable of producing 5hoC, suggesting this base modification is a starting point for glycodiverse cytosine derivatives. Characterizing these cytosine derivatives adds to our understanding of viral anti-defense mechanisms.

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)0.000
metaresearch head score (Gemma)0.000
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 score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

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 science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.014
GPT teacher head0.227
Teacher spread0.212 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicBacteriophages and microbial interactions→French-language works237,207→