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Background: Protein solubility is a precondition for efficient heterologous protein expression at the basis of most industrial applications and for functional interpretation in basic research. However, recurrent formation of inclusion bodies is still an inevitable roadblock in protein science and industry, where only nearly a quarter of proteins can be successfully expressed in soluble form. Despite numerous solubility prediction models having been developed over time, their performance remains unsatisfactory in the context of the current strong increase in available protein sequences. Hence, it is imperative to develop novel and highly accurate predictors that enable the prioritization of highly soluble proteins to reduce the cost of actual experimental work. Results: In this study, we developed a novel tool, DeepSoluE, which predicts protein solubility using a long-short-term memory (LSTM) network with hybrid features composed of physicochemical patterns and distributed representation of amino acids. Comparison results showed that the proposed model achieved more accurate and balanced performance than existing tools. Furthermore, we explored specific features that have a dominant impact on the model performance as well as their interaction effects. Conclusions: DeepSoluE is suitable for the prediction of protein solubility in E. coli; it serves as a bioinformatics tool for prescreening of potentially soluble targets to reduce the cost of wet-experimental studies. The publicly available webserver is freely accessible at . [ABSTRACT FROM AUTHOR]

Background: Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions. Results: Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at . Conclusions: In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) can regulate microRNA activity and are related to various diseases, such as cancer. Functional research on circRNAs is the focus of scientific research. Accurate identification of circRNAs is important for gaining insight into their functions. Although several circRNA prediction models have been developed, their prediction accuracy is still unsatisfactory. Therefore, providing a more accurate computational framework to predict circRNAs and analyse their looping characteristics is crucial for systematic annotation. Results: We developed a novel framework, CircDC, for classifying circRNAs from other lncRNAs. CircDC uses four different feature encoding schemes and adopts a multilayer convolutional neural network and bidirectional long short-term memory network to learn high-order feature representation and make circRNA predictions. The results demonstrate that the proposed CircDC model is more accurate than existing models. In addition, an interpretable analysis of the features affecting the model is performed, and the computational framework is applied to the extended application of circRNA identification. Conclusions: CircDC is suitable for the prediction of circRNA. The identification of circRNA helps to understand and delve into the related biological processes and functions. Feature importance analysis increases model interpretability and uncovers significant biological properties. The relevant code and data in this article can be accessed for free at https://github.com/nmt315320/CircDC.git. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been confirmed to play a vital role in the occurrence and development of diseases. Exploring the relationship between circRNAs and diseases is of far-reaching significance for studying etiopathogenesis and treating diseases. To this end, based on the graph Markov neural network algorithm (GMNN) constructed in our previous work GMNN2CD, we further considered the multisource biological data that affects the association between circRNA and disease and developed an updated web server CircDA and based on the human hepatocellular carcinoma (HCC) tissue data to verify the prediction results of CircDA. Results: CircDA is built on a Tumarkov-based deep learning framework. The algorithm regards biomolecules as nodes and the interactions between molecules as edges, reasonably abstracts multiomics data, and models them as a heterogeneous biomolecular association network, which can reflect the complex relationship between different biomolecules. Case studies using literature data from HCC, cervical, and gastric cancers demonstrate that the CircDA predictor can identify missing associations between known circRNAs and diseases, and using the quantitative real-time PCR (RT-qPCR) experiment of HCC in human tissue samples, it was found that five circRNAs were significantly differentially expressed, which proved that CircDA can predict diseases related to new circRNAs. Conclusions: This efficient computational prediction and case analysis with sufficient feedback allows us to identify circRNA-associated diseases and disease-associated circRNAs. Our work provides a method to predict circRNA-associated diseases and can provide guidance for the association of diseases with certain circRNAs. For ease of use, an online prediction server (http://server.malab.cn/CircDA) is provided, and the code is open-sourced (https://github.com/nmt315320/CircDA.git) for the convenience of algorithm improvement. [ABSTRACT FROM AUTHOR]

Background: RNA 5-methyluridine (m5U) modifications are obtained by methylation at the C5 position of uridine catalyzed by pyrimidine methylation transferase, which is related to the development of human diseases. Accurate identification of m5U modification sites from RNA sequences can contribute to the understanding of their biological functions and the pathogenesis of related diseases. Compared to traditional experimental methods, computational methods developed based on machine learning with ease of use can identify modification sites from RNA sequences in an efficient and time-saving manner. Despite the good performance of these computational methods, there are some drawbacks and limitations. Results: In this study, we have developed a novel predictor, m5U-SVM, based on multi-view features and machine learning algorithms to construct predictive models for identifying m5U modification sites from RNA sequences. In this method, we used four traditional physicochemical features and distributed representation features. The optimized multi-view features were obtained from the four fused traditional physicochemical features by using the two-step LightGBM and IFS methods, and then the distributed representation features were fused with the optimized physicochemical features to obtain the new multi-view features. The best performing classifier, support vector machine, was identified by screening different machine learning algorithms. Compared with the results, the performance of the proposed model is better than that of the existing state-of-the-art tool. Conclusions: m5U-SVM provides an effective tool that successfully captures sequence-related attributes of modifications and can accurately predict m5U modification sites from RNA sequences. The identification of m5U modification sites helps to understand and delve into the related biological processes and functions. [ABSTRACT FROM AUTHOR]