Investigating cross-organism prediction of prokaryotic essential proteins using unsupervised language model and ensemble strategy.

A novel benchmark dataset for enzyme function prediction reveals the limitations of state-of-the-art models

It is demonstrated that modern EC predictors largely fail to distinguish catalytically incompetent variants from functional enzymes, and it is proposed that integrating structure-aware negative examples into both training and benchmarking is critical for developing functionally robust models in computational enzymology.

An enzyme-specific protein language model for catalytic property prediction

This manuscript introduces EnzGFM, an enzyme-specific hybrid model that improves both accuracy and efficiency across multiple prediction tasks and, together with the EnzGFM-Agent pipeline, demonstrates the ability to identify experimentally validated beneficial variants while reducing screening effort.

Evaluating the cross-species transferability and scaling of sequence-to-function predictions in AlphaGenome

This work developed a scoring-approach for AI-agents to autonomously assess AlphaGenome prediction confidence and accurately differentiate between AlphaGenome’s robust sequence-level recognition across species and its current limitations when interpreting un-fine-mapped regulatory variants.

WASP: a pipeline for functional annotation prediction based on AlphaFold structural models

WASP highlights how structural homology can systematically discover annotations missed by sequence-based approaches, predicting protein functions from AlphaFold structures using network-based structural homology and filling metabolic model gaps by mapping 75-100% of orphan reactions.

Genome-scale prediction of context-specific synthetic lethality beyond protein interaction networks

Evo-AA: Evolution-Aware Adaptation of Protein Language Models

Cutting-edge bioinformatics research is increasingly intertwined with pre-trained model techniques. However, achieving superior performance of these models in downstream applications typically requires large amounts of accurately labeled experimental data for fine-tuning, which poses substantial practical challenges due to the difficulty in preparing such datasets at scale. To address this limitation, we propose a novel few-shot fine-tuning framework, the Evolution-Aware Adaptation (Evo-AA). It aligns fine-tuning with pre-training objectives while integrating prompt learning and biological coevolutionary insights. Additionally, we introduce reinforced prompting and lambda ranking loss to further improve performance. Extensive experiments demonstrate that Evo-AA with limited training set, enhances the spearman correlation in fine-tuning tasks, while achieving superior precision and recall rates in homology search tasks. Our findings suggest that Evo-AA holds great potential to drive advancements in protein engineering and computational biology.