Do Protein Transformers Have Biological Intelligence?

Deep neural networks, particularly Transformers, have been widely adopted for predicting the functional properties of proteins. In this work, we focus on exploring whether Protein Transformers can capture biological intelligence among protein sequences. To achieve our goal, we first introduce a protein function dataset, namely Protein-FN, providing over 9000 protein data with meaningful labels. Second, we devise a new Transformer architecture, namely Sequence Protein Transformers (SPT), for computationally efficient protein function predictions. Third, we develop a novel Explainable Artificial Intelligence (XAI) technique called Sequence Score, which can efficiently interpret the decision-making processes of protein models, thereby overcoming the difficulty of deciphering biological intelligence bided in Protein Transformers. Remarkably, even our smallest SPT-Tiny model, which contains only 5.4M parameters, demonstrates impressive predictive accuracy, achieving 94.3% on the Antibiotic Resistance (AR) dataset and 99.6% on the Protein-FN dataset, all accomplished by training from scratch. Besides, our Sequence Score technique helps reveal that our SPT models can discover several meaningful patterns underlying the sequence structures of protein data, with these patterns aligning closely with the domain knowledge in the biology community. We have officially released our Protein-FN dataset on Hugging Face Datasets https://huggingface.co/datasets/Protein-FN/Protein-FN. Our code is available at https://github.com/fudong03/BioIntelligence.

Integrating Secondary Structures Information into Triangular Spatial Relationships (TSR) for Advanced Protein Classification

Protein structures represent the key to deciphering biological functions. The more detailed form of similarity among these proteins is sometimes overlooked by the conventional structural comparison methods. In contrast, further advanced methods, such as Triangular Spatial Relationship (TSR), have been demonstrated to make finer differentiations. Still, the classical implementation of TSR does not provide for the integration of secondary structure information, which is important for a more detailed understanding of the folding pattern of a protein. To overcome these limitations, we developed the SSE-TSR approach. The proposed method integrates secondary structure elements (SSEs) into TSR-based protein representations. This allows an enriched representation of protein structures by considering 18 different combinations of helix, strand, and coil arrangements. Our results show that using SSEs improves the accuracy and reliability of protein classification to varying degrees. We worked with two large protein datasets of 9.2K and 7.8K samples, respectively. We applied the SSE-TSR approach and used a neural network model for classification. Interestingly, introducing SSEs improved performance statistics for Dataset 1, with accuracy moving from 96.0% to 98.3%. For Dataset 2, where the performance statistics were already good, further small improvements were found with the introduction of SSE, giving an accuracy of 99.5% compared to 99.4%. These results show that SSE integration can dramatically improve TSR key discrimination, with significant benefits in datasets with low initial accuracies and only incremental gains in those with high baseline performance. Thus, SSE-TSR is a powerful bioinformatics tool that improves protein classification and understanding of protein function and interaction.