Origins of replication sites (ORIs), which refers to the initiative locations of genomic DNA replication, play essential roles in DNA replication process. Detection of ORIs’ distribution in genome scale is one of key steps to in-depth understanding their regulation mechanisms. In this study, we presented a novel machine learning-based approach called Stack-ORI encompassing 10 cell-specific prediction models for identifying ORIs from four different eukaryotic species (Homo sapiens, Mus musculus, Drosophila melanogaster and Arabidopsis thaliana). For each cell-specific model, we employed 12 feature encoding schemes that cover nucleic acid composition, position-specific and physicochemical properties information. The optimal feature set was identified from each encoding individually and developed their respective baseline models using the eXtreme Gradient Boosting (XGBoost) classifier. Subsequently, the predicted scores of 12 baseline models are integrated as a novel feature vector to train XGBoost and develop the final model. Extensive experimental results show that Stack-ORI achieves significantly better performance as compared with their baseline models on both training and independent datasets. Interestingly, Stack-ORI consistently outperforms existing predictor in all cell-specific models, not only on training but also on independent test. Moreover, our novel approach provides necessary interpretations that help understanding model success by leveraging the powerful SHapley Additive exPlanation algorithm, thus underlining the most important feature encoding schemes significant for predicting cell-specific ORIs.

The prediction of peptide secondary structures is fundamentally important to reveal the functional mechanisms of peptides with potential applications as therapeutic molecules. In this study, we propose a multi-view deep learning method named Peptide Secondary Structure Prediction based on Multi-View Information, Restriction and Transfer learning (PSSP-MVIRT) for peptide secondary structure prediction. To sufficiently exploit discriminative information, we introduce a multi-view fusion strategy to integrate different information from multiple perspectives, including sequential information, evolutionary information and hidden state information, respectively, and generate a unified feature space. Moreover, we construct a hybrid network architecture of Convolutional Neural Network and Bi-directional Gated Recurrent Unit to extract global and local features of peptides. Furthermore, we utilize transfer learning to effectively alleviate the lack of training samples (peptides with experimentally validated structures). Comparative results on independent tests demonstrate that our proposed method significantly outperforms state-of-the-art methods. In particular, our method exhibits better performance at the segment level, suggesting the strong ability of our model in capturing local discriminative information. The case study also shows that our PSSP-MVIRT achieves promising and robust performance in the prediction of new peptide secondary structures. Importantly, we establish a webserver to implement the proposed method, which is currently accessible via http://server.malab.cn/PSSP-MVIRT. We expect it can be a useful tool for the researchers of interest, facilitating the wide use of our method.

Motivation Anticancer peptides (ACPs) have recently emerged as effective anticancer drugs in cancer therapy. Machine-learning-based predictors have been developed to identify ACPs and achieve satisfactory performance. However, existing methods suffer from experience-based feature engineering, which not only restricts the representation ability of the models to a certain extent but also lacks adaptivity for different data, limiting the further improvement of the predictive performance and impacting the robustness of the predictive models. To alleviate the above problems, we propose a novel deep-learning-based predictor named ACPred-LAF, in which we propose a novel multi-sense and multi-scaled embedding algorithm to automatically learn and extract context sequential characteristics of ACPs. Results Through the feature comparative analysis, we demonstrate that our learnable and self-adaptive embedding features are better than hand-crafted features in capturing discriminative information, which can effectively benefit the performance improvement for ACP prediction. In addition, benchmarking comparison results demonstrate that our ACPred-LAF outperforms the state-of-the-art methods both on existing benchmark datasets and our newly constructed dataset. Furthermore, we also prove and validate the robustness of the model via the data interference experiment. To avoid potential evaluation bias, here we construct a new ACP benchmark dataset named ACP-Mixed by integrating existing datasets. We expect our newly constructed dataset to be a golden standard benchmark dataset in this field. To facilitate the use of our model, we develop a web server as the implementation of ACPred-LAF. Availability Our proposed ACPred-LAF, newly constructed benchmark dataset ACP-Mixed are open source collaborative initiatives available in the GitHub repository (https://github.com/TearsWaiting/ACPred-LAF). Besides, a webserver as the implementation of ACPred-LAF that can be accessed via: http://server.malab.cn/ACPred-LAF. Supplementary information Supplementary data are available at Bioinformatics online.

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.

Recently, machine learning methods have been developed to identify various peptide bio-activities. However, due to the lack of experimentally validated peptides, machine learning methods cannot provide a sufficiently trained model, easily resulting in poor generalizability. Furthermore, there is no generic computational framework to predict the bioactivities of different peptides. Thus, a natural question is whether we can use limited samples to build an effective predictive model for different kinds of peptides. To address this question, we propose Mutual Information Maximization Meta-Learning (MIMML), a novel meta-learning-based predictive model for bioactive peptide discovery. Using few samples from various functional peptides, MIMML can sufficiently learn the discriminative information amongst various functions and characterize functional differences. Experimental results show excellent performance of MIMML though using far fewer training samples as compared to the state-of-the-art methods. We also decipher the latent relationships among different kinds of functions to understand what meta-model learned to improve a specific task. In summary, this study is a pioneering work in the field of functional peptide mining and provides the first-of-its-kind solution for few-sample learning problems in biological sequence analysis, accelerating the new functional peptide discovery. The source codes and datasets are available on https://github.com/TearsWaiting/MIMML.