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Record W4416285480 · doi:10.1101/2025.11.16.688692

Inferring binding specificities of human transcription factors with the wisdom of crowds

2025· preprint· en· W4416285480 on OpenAlexaff
Nikita Gryzunov, Dmitry Penzar, Vasilii Kamenets, Valery Vyaltsev, Ivan Kozin, Irina A. Eliseeva, Vladimir Nozdrin, Ilya E. Vorontsov, Sergey Bushuev, Vadim V. Strekalovskikh, Arsenii Zinkevich, Gregory Andrews, Matwej Bedarew, Ido Blass, Dmitry Frolov, Iuliia Lariushina, Jill E. Moore, Yaron Orenstein, German V. Roev, Danil Salimov, Noam Shimshoviz, Ido Tziony, Zhiping Weng, Philipp Bücher, Bart Deplancke, Oriol Fornés, Jan Grau, Ivo Große, Arttu Jolma, Fedor Kolpakov, Vsevolod J. Makeev, Timothy R. Hughes, Ivan V. Kulakovskiy

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsBC Children's HospitalUniversity of British Columbia
Fundersnot available
KeywordsBenchmarkingMotif (music)Deep learningDNA binding siteTranscription factorTranscription (linguistics)

Abstract

fetched live from OpenAlex

DNA motif discovery and, particularly, computational modeling of transcription factor binding motifs, has been a mecca of algorithmic bioinformatics for several decades. Here, we report the results of the largest open community challenge in Inferring BInding Specificities (IBIS), where participants all over the world were invited to construct binding specificity models from multi-assay experimental data for poorly studied human transcription factors. The submissions were rigorously tested against a rich held-out dataset. Benchmarking demonstrated a consistent advantage of properly designed deep learning models over traditional positional weight matrices and other machine learning methods. Yet, the positional weight matrices displayed a surprisingly strong performance out of the box, being only slightly behind the best deep learning models. A post-challenge assessment of a selection of other deep learning methods further solidified this finding. IBIS highlights the power of benchmarking in finding adequate DNA motif representations, emphasizes the pros and cons of various machine learning methods applied to DNA motif modeling, and establishes a rich dataset, benchmarking protocols, and computational framework for a fair cross-platform evaluation of future models of transcription factor binding motifs in DNA sequences.

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)0.008
metaresearch head score (Gemma)0.032
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: none
Teacher disagreement score0.009
Threshold uncertainty score0.042

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0080.032
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.002
Scholarly communication0.0030.003
Open science0.0020.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0020.001

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 head0.012
GPT teacher head0.212
Teacher spread0.200 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenomics and Chromatin Dynamics→French-language works237,207→