N6-methyladenosine (m6A) modification is the most abundant RNA methylation modification and involves various biological processes, such as RNA splicing and degradation. Recent studies have demonstrated the feasibility of identifying m6A peaks using high-throughput sequencing techniques. However, such techniques cannot accurately identify specific methylated sites, which is important for a better understanding of m6A functions. In this study, we develop a novel machine learning-based predictor called M6APred-EL for the identification of m6A sites. To predict m6A sites accurately within genomic sequences, we trained an ensemble of three support vector machine classifiers that explore the position-specific information and physical chemical information from position-specific k-mer nucleotide propensity, physical-chemical properties, and ring-function-hydrogen-chemical properties. We examined and compared the performance of our predictor with other state-of-the-art methods of benchmarking datasets. Comparative results showed that the proposed M6APred-EL performed more accurately for m6A site identification. Moreover, a user-friendly web server that implements the proposed M6APred-EL is well established and is currently available at http://server.malab.cn/M6APred-EL/. It is expected to be a practical and effective tool for the investigation of m6A functional mechanisms.

M6APred-EL: A Sequence-Based Predictor for Identifying N6-methyladenosine Sites Using Ensemble Learning

LncRNA-protein interactions play important roles in post-transcriptional gene regulation, poly-adenylation, splicing and translation. Identification of lncRNA-protein interactions helps to understand lncRNA-related activities. Existing computational methods utilize multiple lncRNA features or multiple protein features to predict lncRNA-protein interactions, but features are not available for all lncRNAs or proteins; most of existing methods are not capable of predicting interacting proteins (or lncRNAs) for new lncRNAs (or proteins), which don't have known interactions. In this paper, we propose the sequence-based feature projection ensemble learning method, "SFPEL-LPI", to predict lncRNA-protein interactions. First, SFPEL-LPI extracts lncRNA sequence-based features and protein sequence-based features. Second, SFPEL-LPI calculates multiple lncRNA-lncRNA similarities and protein-protein similarities by using lncRNA sequences, protein sequences and known lncRNA-protein interactions. Then, SFPEL-LPI combines multiple similarities and multiple features with a feature projection ensemble learning frame. In computational experiments, SFPEL-LPI accurately predicts lncRNA-protein associations and outperforms other state-of-the-art methods. More importantly, SFPEL-LPI can be applied to new lncRNAs (or proteins). The case studies demonstrate that our method can find out novel lncRNA-protein interactions, which are confirmed by literature. Finally, we construct a user-friendly web server, available at http://www.bioinfotech.cn/SFPEL-LPI/.

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SFPEL-LPI: Sequence-based feature projection ensemble learning for predicting LncRNA-protein interactions

Drug-induced hepatotoxicity may cause acute and chronic liver disease, leading to great concern for patient safety. It is also one of the main reasons for drug withdrawal from the market. Toxicogenomics data has been widely used in hepatotoxicity prediction. In our study, we proposed a multi-dose computational model to predict the drug-induced hepatotoxicity based on gene expression and toxicity data. The dose/concentration information after drug treatment is fully utilized in our study based on the dose-response curve, thus a more informative representative of the dose-response relationship is considered. We also proposed a new feature selection method, named MEMO, which is also one important aspect of our multi-dose model in our study, to deal with the high-dimensional toxicogenomics data. We validated the proposed model using the TG-GATEs, which is a large database recording toxicogenomics data from multiple views. The experimental results show that the drug-induced hepatotoxicity can be predicted with high accuracy and efficiency using the proposed predictive model.

Developing a Multi-Dose Computational Model for Drug-Induced Hepatotoxicity Prediction Based on Toxicogenomics Data

Heterogeneous graphs (HGs) also known as heterogeneous information networks have become ubiquitous in real-world scenarios; therefore, HG embedding, which aims to learn representations in a lower-dimension space while preserving the heterogeneous structures and semantics for downstream tasks (e.g., node/graph classification, node clustering, link prediction), has drawn considerable attentions in recent years. In this survey, we perform a comprehensive review of the recent development on HG embedding methods and techniques. We first introduce the basic concepts of HG and discuss the unique challenges brought by the heterogeneity for HG embedding in comparison with homogeneous graph representation learning; and then we systemically survey and categorize the state-of-the-art HG embedding methods based on the information they used in the learning process to address the challenges posed by the HG heterogeneity. In particular, for each representative HG embedding method, we provide detailed introduction and further analyze its pros and cons; meanwhile, we also explore the transformativeness and applicability of different types of HG embedding methods in the real-world industrial environments for the first time. In addition, we further present several widely deployed systems that have demonstrated the success of HG embedding techniques in resolving real-world application problems with broader impacts. To facilitate future research and applications in this area, we also summarize the open-source code, existing graph learning platforms and benchmark datasets. Finally, we explore the additional issues and challenges of HG embedding and forecast the future research directions in this field.

A Survey on Heterogeneous Graph Embedding: Methods, Techniques, Applications and Sources

Antioxidant proteins can be beneficial in disease prevention. More attention has been paid to the functionality of antioxidant proteins. Therefore, identifying antioxidant proteins is important for the study. In our work, we propose a computational method, called SeqSVM, for predicting antioxidant proteins based on their primary sequence features. The features are removed to reduce the redundancy by max relevance max distance method. Finally, the antioxidant proteins are identified by support vector machine (SVM). The experimental results demonstrated that our method performs better than existing methods, with the overall accuracy of 89.46%. Although a proposed computational method can attain an encouraging classification result, the experimental results are verified based on the biochemical approaches, such as wet biochemistry and molecular biology techniques.

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SeqSVM: A Sequence-Based Support Vector Machine Method for Identifying Antioxidant Proteins

Massive studies have indicated that long non-coding RNAs (lncRNAs) are critical for the regulation of cellular biological processes by binding with RNA-related proteins. However, only a few experimentally supported lncRNA-protein associations have been reported. Existing network-based methods are typically focused on intrinsic features of lncRNA and protein but ignore the information implicit in the topologies of biological networks associated with lncRNAs. Considering the limitations in previous methods, we propose PLPIHS, an effective computational method for Predicting lncRNA-Protein Interactions using HeteSim Scores. PLPIHS uses the HeteSim measure to calculate the relatedness score for each lncRNA-protein pair in the heterogeneous network, which consists of lncRNA-lncRNA similarity network, lncRNA-protein association network and protein-protein interaction network. An SVM classifier to predict lncRNA-protein interactions is built with the HeteSim scores. The results show that PLPIHS performs significantly better than the existing state-of-the-art approaches and achieves an AUC score of 0.97 in the leave-one-out validation test. We also compare the performances of networks with different connectivity density and find that PLPIHS performs well across all the networks. Furthermore, we use the proposed method to identify the related proteins for lncRNA MALAT1. Highly-ranked proteins are verified by the biological studies and demonstrate the effectiveness of our method.

Yun Xiao

Papers

Prediction of lncRNA-protein interactions using HeteSim scores based on heterogeneous networks.