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Record W3120180752 · doi:10.1016/j.jmb.2021.166810

ELASPIC2 (EL2): Combining Contextualized Language Models and Graph Neural Networks to Predict Effects of Mutations

2021· article· en· W3120180752 on OpenAlexafffund
Alexey Strokach, Tianyu Lu, Philip M. Kim

Bibliographic record

VenueJournal of Molecular Biology · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Structure and Dynamics
Canadian institutionsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsComputer scienceMachine learningArtificial intelligenceLeverage (statistics)Artificial neural networkLanguage modelWeb serverThe Internet

Abstract

fetched live from OpenAlex

The ELASPIC web server allows users to evaluate the effect of mutations on protein folding and protein-protein interaction on a proteome-wide scale. It uses homology models of proteins and protein-protein interactions, which have been precalculated for several proteomes, and machine learning models, which integrate structural information with sequence conservation scores, in order to make its predictions. Since the original publication of the ELASPIC web server, several advances have motivated a revisiting of the problem of mutation effect prediction. First, progress in neural network architectures and self-supervised pre-trained has resulted in models which provide more informative embeddings of protein sequence and structure than those used by the original version of ELASPIC. Second, the amount of training data has increased several-fold, largely driven by advances in deep mutation scanning and other multiplexed assays of variant effect. Here, we describe two machine learning models which leverage the recent advances in order to achieve superior accuracy in predicting the effect of mutation on protein folding and protein-protein interaction. The models incorporate features generated using pre-trained transformer- and graph convolution-based neural networks, and are trained to optimize a ranking objective function, which permits the use of heterogeneous training data. The outputs from the new models have been incorporated into the ELASPIC web server, available at http://elaspic.kimlab.org.

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 score0.256
Threshold uncertainty score0.433

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 head0.004
GPT teacher head0.256
Teacher spread0.252 · 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

Citations44
Published2021
Admission routes2
Has abstractyes

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