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Record W4417523770 · doi:10.1093/bib/bbaf685

Component puzzle protein–protein interaction prediction

2025· article· en· W4417523770 on OpenAlexaff
SeyedMohsen Hosseini, G. Brian Golding, Lucian Ilie

Bibliographic record

VenueBriefings in Bioinformatics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsMcMaster UniversityWestern University
Fundersnot available
KeywordsSource codeKey (lock)Component (thermodynamics)Code (set theory)Node (physics)Deep learning

Abstract

fetched live from OpenAlex

Proteins primarily perform their functions through interactions with other proteins, making the accurate prediction of protein-protein interactions (PPIs) a fundamental problem. Experimental methods for determining PPIs are often slow and expensive, which has driven significant efforts to improve the performance of computational methods in this field. While many methods have been designed, recent thorough investigations proved that the existing methods learn exclusively from sequence similarities and node degrees. When such data leakage is avoided, performances were shown to become random. We introduce C3PI, a novel sequence-based deep learning framework designed for predicting PPIs. C3PI uses as input ProtT5 protein embeddings into a complex architecture that includes two novel components, a puzzler and an entangler, which significantly enhance the model's performance. Through extensive comparisons with state-of-the-art methods across many datasets, C3PI consistently outperforms competing approaches, especially in key metrics such as AUPRC and AUROC. Most importantly, C3PI is the first PPI prediction method to achieve a significant improvement over random on the leakage-free gold standard dataset. C3PI is available as a web server at c3pi.csd.uwo.ca and source code from github.com/lucian-ilie/C3PI.

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: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.008
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.000
Scholarly communication0.0010.002
Open science0.0020.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0080.005

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 head0.007
GPT teacher head0.227
Teacher spread0.221 · 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
GenreMethods

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

Citations1
Published2025
Admission routes1
Has abstractyes

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