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DistilProtBert: A distilled protein language model used to distinguish between real proteins and their randomly shuffled counterparts

10 May 2022bioRxiv 2022 5archive 2025-07-28

Yaron Geffen, Yanay Ofran, Ron Unger

Recently, Deep Learning models, initially developed in the field of Natural Language Processing (NLP), were applied successfully to analyze protein sequences. A major drawback of these models is their size in terms of the number of parameters needed to be fitted and the amount of computational resources they require. Recently, "distilled" models using the concept of student and teacher networks have been widely used in NLP. Here, we adapted this concept to the problem of protein sequence analysis, by developing DistilProtBert, a distilled version of the successful ProtBert model. Implementing this approach, we reduced the size of the network and the running time by 50%, and the computational resources needed for pretraining by 98% relative to ProtBert model. Using two published tasks, we showed that the performance of the distilled model approaches that of the full model. We next tested the ability of DistilProtBert to distinguish between real and random protein sequences. The task is highly challenging if the composition is maintained on the level of singlet, doublet and triplet amino acids. Indeed, traditional machine learning algorithms have difficulties with this task. Here, we show that DistilProtBert preforms very well on singlet, doublet, and even triplet-shuffled versions of the human proteome, with AUC of 0.92, 0.91, and 0.87 respectively. Finally, we suggest that by examining the small number of false-positive classifications (i.e., shuffled sequences classified as proteins by DistilProtBert) we may be able to identify de-novo potential natural-like proteins based on random shuffling of amino acid sequences.

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Tasks

Dimensionality ReductionKnowledge DistillationLanguage ModelingLanguage ModellingProtein Language ModelProtein Secondary Structure Prediction

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Results from the paper archive 2025-07-28

TaskDatasetModelMetricValueRank at snapshotLeaderboardReport
Protein Secondary Structure Prediction CASP12 DistilProtBert Q3 0.72 #4 of 4 Archive leaderboard report
Protein Secondary Structure Prediction CB513 DistilProtBert Q3 0.79 #10 of 10 Archive leaderboard report
Protein Secondary Structure Prediction TS115 DistilProtBert Q3 0.81 #4 of 4 Archive leaderboard report

Ranks are positions in the archive's leaderboards as they stood at the 2025-07-28 snapshot. Results published since then are not among these rows, so a rank here is not a current standing.

Methods

Absolute Position EncodingsAdamAttentionDense ConnectionsDistilBERTDropoutKnowledge DistillationLayer NormalizationLinear LayerMulti-Head AttentionPosition-Wise Feed-Forward LayerRAdamResidual ConnectionSoftmaxTransformer

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