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Record W4410139616 · doi:10.1038/s41467-025-58862-8

Predictive biophysical neural network modeling of a compendium of in vivo transcription factor DNA binding profiles for Escherichia coli

2025· article· en· W4410139616 on OpenAlexafffund
Patrick Lally, Laura Gómez-Romero, Víctor H. Tierrafría, Patricia Aquino, Claire Rioualen, Xiaoman Zhang, Sunyoung Kim, Gabriele Baniulyte, Jonathan Plitnick, Carol Smith, Mohan Babu, Julio Collado‐Vides, Joseph T. Wade, James E. Galagan

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiffusion and Search Dynamics
Canadian institutionsUniversity of Regina
FundersNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaGovernment of CanadaConsejo Nacional de Ciencia y TecnologíaNational Institutes of HealthNational Institute of Biomedical Imaging and BioengineeringConsejo Nacional de Ciencia y Tecnología, GuatemalaUniversidad Nacional Autónoma de México
KeywordsCompendiumEscherichia coliTranscription factorComputational biologyDNAIn vivoDNA binding siteBiologyGeneticsBioinformaticsPromoterGeneGene expressionGeography

Abstract

fetched live from OpenAlex

The DNA binding of most Escherichia coli Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of in vivo DNA binding for 139 E. coli TFs using ChIP-Seq. We use these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence. BoltzNet mirrors a quantitative biophysical model and provides directly interpretable predictions genome-wide at nucleotide resolution. We use BoltzNet to quantitatively design novel binding sites, which we validate with biophysical experiments on purified protein. We generate models for 124 TFs that provide insight into global features of TF binding, including clustering of sites, the role of accessory bases, the relevance of weak sites, and the background affinity of the genome. Our paper provides new paradigms for studying TF-DNA binding and for the development of biophysically motivated neural networks. The authors describe BoltzNet, a neural network that learns the energy of transcription factor (TF)-DNA binding from genomic data and can be used to design new binding sites. They report the in vivo mapping and BoltzNet modeling of 139 E. coli TFs.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.020
Threshold uncertainty score0.040

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 integrity0.0010.001
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 head0.020
GPT teacher head0.307
Teacher spread0.288 · 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 designSimulation or modeling
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

Citations8
Published2025
Admission routes2
Has abstractyes

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