One of the main problems with the joint use of multiple drugs is that it may cause adverse drug interactions and side effects that damage the body. Therefore, it is important to predict potential drug interactions. However, most of the available prediction methods can only predict whether two drugs interact or not, whereas few methods can predict interaction events between two drugs. Accurately predicting interaction events of two drugs is more useful for researchers to study the mechanism of the interaction of two drugs. In the present study, we propose a novel method, MDF-SA-DDI, which predicts drug–drug interaction (DDI) events based on multi-source drug fusion, multi-source feature fusion and transformer self-attention mechanism. MDF-SA-DDI is mainly composed of two parts: multi-source drug fusion and multi-source feature fusion. First, we combine two drugs in four different ways and input the combined drug feature representation into four different drug fusion networks (Siamese network, convolutional neural network and two auto-encoders) to obtain the latent feature vectors of the drug pairs, in which the two auto-encoders have the same structure, and their main difference is the number of neurons in the input layer of the two auto-encoders. Then, we use transformer blocks that include self-attention mechanism to perform latent feature fusion. We conducted experiments on three different tasks with two datasets. On the small dataset, the area under the precision–recall-curve (AUPR) and F1 scores of our method on task 1 reached 0.9737 and 0.8878, respectively, which were better than the state-of-the-art method. On the large dataset, the AUPR and F1 scores of our method on task 1 reached 0.9773 and 0.9117, respectively. In task 2 and task 3 of two datasets, our method also achieved the same or better performance as the state-of-the-art method. More importantly, the case studies on five DDI events are conducted and achieved satisfactory performance. The source codes and data are available at https://github.com/ShenggengLin/MDF-SA-DDI.

Gene Ontology (GO) has been widely used to annotate functions of proteins and understand their biological roles. Currently only $<1%$ of >70 million proteins in UniProtKB have experimental GO annotations, implying the strong necessity of automated function prediction (AFP) of proteins, where AFP is a hard multilabel classification problem due to one protein with a diverse number of GO terms. Most of these proteins have only sequences as input information, indicating the importance of sequence-based AFP (SAFP: sequences are the only input). Furthermore, homology-based SAFP tools are competitive in AFP competitions, while they do not necessarily work well for so-called difficult proteins, which have $<60%$ sequence identity to proteins with annotations already. Thus, the vital and challenging problem now is how to develop a method for SAFP, particularly for difficult proteins. The key of this method is to extract not only homology information but also diverse, deep-rooted information/evidence from sequence inputs and integrate them into a predictor in a both effective and efficient manner. We propose GOLabeler, which integrates five component classifiers, trained from different features, including GO term frequency, sequence alignment, amino acid trigram, domains and motifs, and biophysical properties, etc., in the framework of learning to rank (LTR), a paradigm of machine learning, especially powerful for multilabel classification. The empirical results obtained by examining GOLabeler extensively and thoroughly by using large-scale datasets revealed numerous favorable aspects of GOLabeler, including significant performance advantage over state-of-the-art AFP methods. http://datamining-iip.fudan.edu.cn/golabeler. Supplementary data are available at Bioinformatics online.

Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search method with only sequences as input. PLMSearch uses deep representations from a pre-trained protein language model and trains the similarity prediction model with a large number of real structure similarity. This enables PLMSearch to capture the remote homology information concealed behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with dissimilar sequences but similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch.

As one of the state-of-the-art automated function prediction (AFP) methods, NetGO 2.0 integrates multi-source information to improve the performance. However, it mainly utilizes the proteins with experimentally supported functional annotations without leveraging valuable information from a vast number of unannotated proteins. Recently, protein language models have been proposed to learn informative representations [e.g., Evolutionary Scale Modeling (ESM)-1b embedding] from protein sequences based on self-supervision. Here, we represented each protein by ESM-1b and used logistic regression (LR) to train a new model, LR-ESM, for AFP. The experimental results showed that LR-ESM achieved comparable performance with the best-performing component of NetGO 2.0. Therefore, by incorporating LR-ESM into NetGO 2.0, we developed NetGO 3.0 to improve the performance of AFP extensively. NetGO 3.0 is freely accessible at https://dmiip.sjtu.edu.cn/ng3.0.

Pseudouridylation is the most prevalent type of posttranscriptional modification in various stable RNAs of all organisms, which significantly affects many cellular processes that are regulated by RNA. Thus, accurate identification of pseudouridine (Ψ) sites in RNA will be of great benefit for understanding these cellular processes. Due to the low efficiency and high cost of current available experimental methods, it is highly desirable to develop computational methods for accurately and efficiently detecting Ψ sites in RNA sequences. However, the predictive accuracy of existing computational methods is not satisfactory and still needs improvement. In this study, we developed a new model, PseUI, for Ψ sites identification in three species, which are H. sapiens, S. cerevisiae, and M. musculus. Firstly, five different kinds of features including nucleotide composition (NC), dinucleotide composition (DC), pseudo dinucleotide composition (pseDNC), position-specific nucleotide propensity (PSNP), and position-specific dinucleotide propensity (PSDP) were generated based on RNA segments. Then, a sequential forward feature selection strategy was used to gain an effective feature subset with a compact representation but discriminative prediction power. Based on the selected feature subsets, we built our model by using a support vector machine (SVM). Finally, the generalization of our model was validated by both the jackknife test and independent validation tests on the benchmark datasets. The experimental results showed that our model is more accurate and stable than the previously published models. We have also provided a user-friendly web server for our model at http://zhulab.ahu.edu.cn/PseUI , and a brief instruction for the web server is provided in this paper. By using this instruction, the academic users can conveniently get their desired results without complicated calculations. In this study, we proposed a new predictor, PseUI, to detect Ψ sites in RNA sequences. It is shown that our model outperformed the existing state-of-art models. It is expected that our model, PseUI, will become a useful tool for accurate identification of RNA Ψ sites.