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Record W4413817707 · doi:10.1371/journal.pcbi.1013376

The R-loop grammar predicts R-loop formation under different topological constraints

2025· article· en· W4413817707 on OpenAlexafffund
Margherita Maria Ferrari, Svetlana Poznanović, Manda Riehl, Jacob Lusk, Stella R. Hartono, Georgina Gonzalez-Isunza, Frédéric Chédin, Mariel Vázquez, Nataša Jonoska

Bibliographic record

VenuePLoS Computational Biology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsUniversity of Manitoba
FundersNatural Sciences and Engineering Research Council of CanadaNational Institute of General Medical SciencesDirectorate for Mathematical and Physical SciencesDirectorate for Computer and Information Science and EngineeringUniversity of ManitobaSimons FoundationW. M. Keck FoundationNational Institutes of HealthAssociation for Women in MathematicsNational Science Foundation
KeywordsLoop (graph theory)Loop fusionGrammarLoop fissionTopology (electrical circuits)DNABiologyGeneComputational biologyGeneticsComputer sciencePhysicsMathematicsCombinatoricsLinguistics

Abstract

fetched live from OpenAlex

R-loops are transient three-stranded nucleic acids that form during transcription when the nascent RNA hybridizes with the template DNA, freeing the non-template strand of the DNA. There is growing evidence that R-loops play important roles in physiological processes such as the regulation of gene expression, and that they contribute to chromosomal instability and disease. It is known that R-loop formation is influenced by both the sequence and the topology of the DNA substrate, but many questions remain about how R-loops form and the three-dimensional structures that they adopt. Here we represent an R-loop as a word in a formal grammar, the R-loop grammar. We use the R-loop grammar to predict R-loop formation. We train the R-loop grammar on experimental data obtained by single-molecule R-loop footprinting and sequencing (SMRF-seq). Despite not explicitly encoding topological information, the R-loop grammar accurately predicts R-loop formation on plasmids with varying starting topologies and outperforms previous methods in R-loop prediction.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.187
Threshold uncertainty score0.377

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 science0.0000.000
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 head0.019
GPT teacher head0.261
Teacher spread0.243 · 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

Citations2
Published2025
Admission routes2
Has abstractyes

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