Identifying the protein-peptide binding residues is fundamentally important to understand the mechanisms of protein functions and explore drug discovery. Although several computational methods have been developed, they highly rely on third-party tools or information for feature design, easily resulting in low computational efficacy and suffering from low predictive performance. To address the limitations, we propose PepBCL, a novel BERT (Bidirectional Encoder Representation from Transformers)-based Contrastive Learning framework to predict the protein-Peptide binding residues based on protein sequences only. PepBCL is an end-to-end predictive model that is independent of designed features. Specifically, we introduce a well pre-trained protein language model that can automatically extract and learn high-latent representations of protein sequences relevant for protein structure and functions. Further, we design a novel contrastive learning module to optimize the feature representations of binding residues underlying the imbalanced dataset. We demonstrate that our proposed method significantly outperforms the state-of-the-art methods under benchmarking comparison, and achieves more robust performance. Moreover, we found that we further improve the performance via the integration of traditional features and our learnt features. Our results highlight the flexibility and adaptability of deep learning-based protein language model to capture both conserved and non-conserved sequential characteristics of peptide-binding residues. Interestingly, we demonstrate that peptide-binding residues in local sequential regions have more specific sequential patterns as compared with other protein-ligand binding residues, which potentially provides functional difference. Finally, to facilitate the use of our method, we establish an online predictive platform as the implementation of the proposed PepBCL, which is now available at http://server.wei-group.net/PepBCL/. Availability https://github.com/Ruheng-W/PepBCL Supplementary information Supplementary data are available at Bioinformatics online.
In this study, we propose iDNA-ABF, a multi-scale deep biological language learning model that enables the interpretable prediction of DNA methylations based on genomic sequences only. Benchmarking comparisons show that our iDNA-ABF outperforms state-of-the-art methods for different methylation predictions. Importantly, we show the power of deep language learning in capturing both sequential and functional semantics information from background genomes. Moreover, by integrating the interpretable analysis mechanism, we well explain what the model learns, helping us build the mapping from the discovery of important sequential determinants to the in-depth analysis of their biological functions.
Here, we present DeepBIO, the first-of-its-kind automated and interpretable deep-learning platform for high-throughput biological sequence functional analysis. DeepBIO is a one-stop-shop web service that enables researchers to develop new deep-learning architectures to answer any biological question. Specifically, given any biological sequence data, DeepBIO supports a total of 42 state-of-the-art deep-learning algorithms for model training, comparison, optimization and evaluation in a fully automated pipeline. DeepBIO provides a comprehensive result visualization analysis for predictive models covering several aspects, such as model interpretability, feature analysis and functional sequential region discovery. Additionally, DeepBIO supports nine base-level functional annotation tasks using deep-learning architectures, with comprehensive interpretations and graphical visualizations to validate the reliability of annotated sites. Empowered by high-performance computers, DeepBIO allows ultra-fast prediction with up to million-scale sequence data in a few hours, demonstrating its usability in real application scenarios. Case study results show that DeepBIO provides an accurate, robust and interpretable prediction, demonstrating the power of deep learning in biological sequence functional analysis. Overall, we expect DeepBIO to ensure the reproducibility of deep-learning biological sequence analysis, lessen the programming and hardware burden for biologists and provide meaningful functional insights at both the sequence level and base level from biological sequences alone. DeepBIO is publicly available at https://inner.wei-group.net/DeepBIO.
Motivation DNA methylation plays an important role in epigenetic modification, the occurrence, and the development of diseases. Therefore, the identification of DNA methylation sites is critical for better understanding and revealing their functional mechanisms. To date, several machine learning and deep learning methods have been developed for the prediction of different methylation types. However, they still highly rely on manual features, which can largely limit the high-latent information extraction. Moreover, most of them are designed for one specific methylation type, and therefore cannot predict multiple methylation sites in multiple species simultaneously. In this study, we propose iDNA-ABT, an advanced deep learning model that utilizes adaptive embedding based on bidirectional transformers for language understanding together with a novel transductive information maximization (TIM) loss. Results Benchmark results show that our proposed iDNA-ABT can automatically and adaptively learn the distinguishing features of biological sequences from multiple species, and thus perform significantly better than the state-of-the-art methods in predicting three different DNA methylation. In addition, TIM loss is proven to be effective in dichotomous tasks via the comparison experiment. Furthermore, we verify that our features have strong adaptability and robustness to different species through comparison of adaptive embedding and six handcrafted feature encodings. Importantly, our model shows great generalization ability in different species, demonstrating that our model can adaptively capture the cross-species differences and improve the predictive performance. For the convenient use of our method, we further established an online webserver as the implementation of the proposed iDNA-ABT. Availability our proposed iDNA-ABT, which is now freely accessible via http://server.wei-group.net/iDNA_ABT and our source codes are available in the GitHub repository (https://github.com/YUYING07/iDNA_ABT) Supplementary information Supplementary data are available at Bioinformatics online.
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