Lightweight ProteinUnet2 network for protein secondary structure prediction: a step towards proper evaluation

Abstract

Background: The prediction of protein secondary structures is a crucial and significant step for ab initio tertiary structure prediction which delivers the information about proteins activity and functions. As the experimental methods are expensive and sometimes impossible, many SS predictors, mainly based on different machine learning methods have been proposed for many years. Currently, most of the top methods use evolutionary-based input features produced by PSSM and HHblits software, although quite recently the embeddings—the new description of protein sequences generated by language models (LM) have appeared that could be leveraged as input features. Apart from input features calculation, the top models usually need extensive computational resources for training and prediction and are barely possible to run on a regular PC. SS prediction as the imbalanced classification problem should not be judged by the commonly used Q3/Q8 metrics. Moreover, as the benchmark datasets are not random samples, the classical statistical null hypothesis testing based on the Neyman–Pearson approach is not appropriate. Results: We present a lightweight deep network ProteinUnet2 for SS prediction which is based on U-Net convolutional architecture and evolutionary-based input features (from PSSM and HHblits) as well as SPOT-Contact features. Through an extensive evaluation study, we report the performance of ProteinUnet2 in comparison with top SS prediction methods based on evolutionary information (SAINT and SPOT-1D). We also propose a new statistical methodology for prediction performance assessment based on the significance from Fisher–Pitman permutation tests accompanied by practical significance measured by Cohen’s effect size. Conclusions: Our results suggest that ProteinUnet2 architecture has much shorter training and inference times while maintaining results similar to SAINT and SPOT-1D predictors. Taking into account the relatively long times of calculating evolutionary-based features (from PSSM in particular), it would be worth conducting the predictive ability tests on embeddings as input features in the future. We strongly believe that our proposed here statistical methodology for the evaluation of SS prediction results will be adopted and used (and even expanded) by the research community.