StructuralDPPIV: a novel deep learning model based on atom structure for predicting dipeptidyl peptidase-IV inhibitory peptides.

MOTIVATION: Diabetes is a chronic metabolic disorder that has been a major cause of blindness, kidney failure, heart attacks, stroke, and lower limb amputation across the world. To alleviate the impact of diabetes, researchers have developed the next generation of anti-diabetic drugs, known as dipeptidyl peptidase IV inhibitory peptides (DPP-IV-IPs). However, the discovery of these promising drugs has been restricted due to the lack of effective peptide-mining tools. RESULTS: Here, we presented StructuralDPPIV, a deep learning model designed for DPP-IV-IP identification, which takes advantage of both molecular graph features in amino acid and sequence information. Experimental results on the independent test dataset and two wet experiment datasets show that our model outperforms the other state-of-art methods. Moreover, to better study what StructuralDPPIV learns, we used CAM technology and perturbation experiment to analyze our model, which yielded interpretable insights into the reasoning behind prediction results. AVAILABILITY AND IMPLEMENTATION: The project code is available at https://github.com/WeiLab-BioChem/Structural-DPP-IV.

Rm-LR: A long-range-based deep learning model for predicting multiple types of RNA modifications.

Recent research has highlighted the pivotal role of RNA post-transcriptional modifications in the regulation of RNA expression and function. Accurate identification of RNA modification sites is important for understanding RNA function. In this study, we propose a novel RNA modification prediction method, namely Rm-LR, which leverages a long-range-based deep learning approach to accurately predict multiple types of RNA modifications using RNA sequences only. Rm-LR incorporates two large-scale RNA language pre-trained models to capture discriminative sequential information and learn local important features, which are subsequently integrated through a bilinear attention network. Rm-LR supports a total of ten RNA modification types (m6A, m1A, m5C, m5U, m6Am, Ψ, Am, Cm, Gm, and Um) and significantly outperforms the state-of-the-art methods in terms of predictive capability on benchmark datasets. Experimental results show the effectiveness and superiority of Rm-LR in prediction of various RNA modifications, demonstrating the strong adaptability and robustness of our proposed model. We demonstrate that RNA language pretrained models enable to learn dense biological sequential representations from large-scale long-range RNA corpus, and meanwhile enhance the interpretability of the models. This work contributes to the development of accurate and reliable computational models for RNA modification prediction, providing insights into the complex landscape of RNA modifications.

Explainable Deep Hypergraph Learning Modeling the Peptide Secondary Structure Prediction.

Accurately predicting peptide secondary structures remains a challenging task due to the lack of discriminative information in short peptides. In this study, PHAT is proposed, a deep hypergraph learning framework for the prediction of peptide secondary structures and the exploration of downstream tasks. The framework includes a novel interpretable deep hypergraph multi-head attention network that uses residue-based reasoning for structure prediction. The algorithm can incorporate sequential semantic information from large-scale biological corpus and structural semantic information from multi-scale structural segmentation, leading to better accuracy and interpretability even with extremely short peptides. The interpretable models are able to highlight the reasoning of structural feature representations and the classification of secondary substructures. The importance of secondary structures in peptide tertiary structure reconstruction and downstream functional analysis is further demonstrated, highlighting the versatility of our models. To facilitate the use of the model, an online server is established which is accessible via http://inner.wei-group.net/PHAT/. The work is expected to assist in the design of functional peptides and contribute to the advancement of structural biology research.