N6-methyladenosine (m6A) can significantly affect RNA expression, gene regulation, and determination of cell fate. As a common and abundant post-transcriptional modification (PTM) of RNA, m6A is also closely associated with the occurrence of numerous diseases. Thus, identifying the m6A modification site in the RNA sequence is a prerequisite for related research. High-throughput sequencing technology has high requirements and low cost performance. Computational methods have made encouraging progress in site prediction. However, most models only consider the effects of different species, ignoring the simultaneous exploration of RNA modifications in different tissues within the same species. We develop and validate a fuzzy system based on Block Sparse Bayesian Learning (BSBL), named BSBL-TSK-FS, which is a powerful sequence-level m6A prediction model. We introduce a Bayesian method that provides a posterior probability output to produce more sparse solutions so that the model has higher accuracy. The model classifies the m6A sites in several tissues of mouse, human, and rat. Under the five-fold cross-validation method (5-CV), the precision of the BSBL-TSK-FS model is 0.84∼0.95. The accuracy of our model improves by 9.4% over the existing SOTA predictors. BSBL-TSK-FS achieves superior performance over current SOTA methods. Finally, in order to verify the generalizability of the model, we carry out cross-species tests, and the results prove the robustness and adaptability of the model. An accurate and reliable sequence modification prediction model is developed to better understand the complex landscape of methylation modification.

In recent years, numerous studies have demonstrated a close connection between human diseases and the regulation of non-coding RNAs (ncRNAs). Predicting potential ncRNAs associated with disease can help provide critical information for diagnosis and treatment of disease, leading to better disease analysis and prevention. Building good algorithms for predicting associations between ncRNAs and disease is critical. Many current algorithms have poor performance in identifying the association between ncRNAs and diseases. As a method for predicting the association between ncRNAs and diseases, we develop a Matrix Factorization method based on the Correntropy Induced Loss (C-loss) function (C-lossMF). In our model, we first construct ncRNA similarity matrix and disease similarity matrix by considering some important similarity information, and extract effective information of ncRNA and disease from them. Next, we perform matrix decomposition of ncRNA-disease association matrix and apply $L2$ loss and C-loss. Then we add collaborative regularization of RNA similarity matrix and the collaborative regularization of disease similarity matrix to take full advantage of the information in the similarity matrix. In particular, we propose a method that combines semi-quadratic optimization and gradient descent to optimize the model. In the experiments, we utilize the five-fold cross validation method on four datasets to evaluate the performance of C-lossMF. Comparing this model with other advanced models, the results show that it performs better.

In many biological processes, N6-methyladenosine (m6A) plays a critical role. Experimental methods for identifying m6A sites have proven to be costly, and existing computational methods still require improvement. To address these challenges, we develop a novel computational method called structured sparse regularization-based fuzzy hierarchical echo state network to identify m6A sites in mammals. We apply fuzzy systems to deep learning. Compared with traditional fuzzy inference systems, this deep fuzzy network has the ability to generate feature representations. Echo state network (ESN) is a special type of recurrent neural network, which consists of an input layer, a randomly generated large fixed hidden layer (called a reservoir), and an adaptive output layer. The advantages of our method over ESNs are that it is capable of mining and capturing hidden features layer-by-layer within reservoirs and has better approximation performance. In order to remove redundancy, the output layer weights are trained by structured sparse learning, which enhances the generalizability and robustness of the method. Evaluation of our method by testing it on tissue-specific datasets shows that it outperforms existing tools.

As an epigenetic modification that plays an important role in modifying gene function and controlling gene expression during cell development, DNA N4-methylcytosine (4mC) is still lack of researching. It is therefore necessary to accurately predict the 4mC sites to make fully aware of its mechanism and function. In this paper, we propose a novel model which is called Structural Sparse Regularized Random Vector Functional Link Network (SSR-RVFL) for predicting 4mC sites. Compared with other state-of-the-art methods, SSR-RVFL performs better and achieves higher prediction accuracy. There are total six benchmark datasets used in the experiments, namely C.elegans, D.elanogaster, E.coli, A.thaliana G.subterraneus and G.pickeringii. Our model improves the accuracy by 0.42%, 0.45%, 0.48%, 0.91%, 0.66% and 0.7% on these six benchmark datasets respectively, so it can be regarded as a more effective prediction tool.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool in genomics research, enabling the analysis of gene expression at the individual cell level. However, scRNA-seq data often suffer from a high rate of dropouts, where certain genes fail to be detected in specific cells due to technical limitations. This missing data can introduce biases and hinder downstream analysis. To overcome this challenge, the development of effective imputation methods has become crucial in the field of scRNA-seq data analysis. Here, we propose an imputation method based on robust and non-negative matrix factorization (scRNMF). Instead of other matrix factorization algorithms, scRNMF integrates two loss functions: L2 loss and C-loss. The L2 loss function is highly sensitive to outliers, which can introduce substantial errors. We utilize the C-loss function when dealing with zero values in the raw data. The primary advantage of the C-loss function is that it imposes a smaller punishment for larger errors, which results in more robust factorization when handling outliers. Various datasets of different sizes and zero rates are used to evaluate the performance of scRNMF against other state-of-the-art methods. Our method demonstrates its power and stability as a tool for imputation of scRNA-seq data.

DNA-binding proteins (DBPs) have a significant impact on many life activities, so identification of DBPs is a crucial issue. And it is greatly helpful to understand the mechanism of protein-DNA interactions. In traditional experimental methods, it is significant time-consuming and labor-consuming to identify DBPs. In recent years, many researchers have proposed lots of different DBP identification methods based on machine learning algorithm to overcome shortcomings mentioned above. However, most existing methods cannot get satisfactory results. In this paper, we focus on developing a new predictor of DBPs, called Multi-View Hypergraph Restricted Kernel Machines (MV-H-RKM). In this method, we extract five features from the three views of the proteins. To fuse these features, we couple them by means of the shared hidden vector. Besides, we employ the hypergraph regularization to enforce the structure consistency between original features and the hidden vector. Experimental results show that the accuracy of MV-H-RKM is 84.09% and 85.48% on PDB1075 and PDB186 data set respectively, and demonstrate that our proposed method performs better than other state-of-the-art approaches. The code is publicly available at https://github.com/ShixuanGG/MV-H-RKM.

Membrane proteins are the main undertaker of biomembrane functions and play a vital role in many biological activities of organisms. Prediction of membrane protein types has a great help in determining the function of proteins and understanding the interactions of membrane proteins. However, the biochemical experiment is expensive and not suitable for the large-scale identification of membrane protein types. Therefore, computational methods were used to improve the efficiency of biological experiments. Most existing computational methods only use a single feature of protein, or use multiple features but do not integrate these well. In our study, the protein sequence is described via three different views (features), including amino acid composition, evolutionary information and physicochemical properties of amino acids. To exploit information among all views (features), we introduce a coupling strategy for Kernel Sparse Representation based Classification (KSRC) and construct a new model called Multi-view KSRC (MvKSRC). We implement our method on 4 benchmark data sets of membrane proteins. The comparison results indicate that our method is much superior to all existing methods.

The detection of therapeutic peptides is usually a biochemical experimental method, which is time-consuming and labor-intensive. Lots of computational biology methods had been proposed to solve the problem of therapeutic peptide prediction. However, the existing methods did not consider the processing of noisy samples. We propose a kernel risk-sensitive mean p-power error-based echo state network with sparse learning (KRP-ESN-SL). An efficient iterative optimization algorithm is used to train the model. The KRP-ESN-SL has better performance than other methods.

In the entire life cycle of drug development, the side effect is one of the major failure factors. Severe side effects of drugs that go undetected until the post-marketing stage leads to around two million patient morbidities every year in the United States. Therefore, there is an urgent need for a method to predict side effects of approved drugs and new drugs. Following this need, we present a new predictor for finding side effects of drugs. Firstly, multiple similarity matrices are constructed based on the association profile feature and drug chemical structure information. Secondly, these similarity matrices are integrated by Centered Kernel Alignment-based Multiple Kernel Learning algorithm. Then, Weighted K nearest known neighbors is utilized to complement the adjacency matrix. Next, we construct Restricted Boltzmann machines (RBM) in drug space and side effect space, respectively, and apply a penalized maximum likelihood approach to train model. At last, the average decision rule was adopted to integrate predictions from RBMs. Comparison results and case studies demonstrate, with four benchmark datasets, that our method can give a more accurate and reliable prediction result.

Current human biomedical research shows that human diseases are closely related to non-coding RNAs, so it is of great significance for human medicine to study the relationship between diseases and non-coding RNAs. Current research has found associations between non-coding RNAs and human diseases through a variety of effective methods, but most of the methods are complex and targeted at a single RNA or disease. Therefore, we urgently need an effective and simple method to discover the associations between non-coding RNAs and human diseases. In this paper, we propose a sparse regularized joint projection model (SRJP) to identify the associations between non-coding RNAs and diseases. First, we extract information through a series of ncRNA similarity matrices and disease similarity matrices and assign average weights to the similarity matrices of the two sides. Then we decompose the similarity matrices of the two spaces into low-rank matrices and put them into SRJP. In SRJP, we innovatively use the projection matrix to combine the ncRNA side and the disease side to identify the associations between ncRNAs and diseases. Finally, the regularization term in SRJP effectively improves the robustness and generalization ability of the model. We test our model on different datasets involving three types of ncRNAs: circRNA, microRNA and long non-coding RNA. The experimental results show that SRJP has superior ability to identify and predict the associations between ncRNAs and diseases.

DNA-binding proteins (DBPs) are of great significance in many basic cellular processes. Experiment-based methods for identifying DBPs are costly and time-consuming. To deal with large-scale DBP identification tasks, a variety of computation-based methods have been developed. Inspired by previous work, we propose a multiple Laplacian regularized support vector machine with local behavior similarity (MLapSVM-LBS) to predict DBP. We serially combine three features that are extracted from protein sequences (including PsePSSM, GE, NMBAC) and feed them into MLapSVM-LBS. Based on human behavior learning theory, MLapSVM-LBS can better represent the relationship between samples through local behavior similarity. We introduce a new edge weight calculation method that takes label information into consideration. In addition, a local distribution parameter reflecting the underlying probability distribution of a sample’s neighborhood is also employed. To further improve the robustness of the model, we utilize multiple Laplacian regularization to build a multigraph model in which five Laplacian graphs are constructed with local behavior similarity by changing the neighborhood size. To appraise the performance of our model, MLapSVM-LBS is trained and tested on the PDB186, PDB1075, PDB2272 and PDB14189 datasets. On two independent testing sets (PDB186 and PDB2272), our method reaches the accuracies of 0.887 and 0.712, respectively. The good results on both datasets demonstrate the reliable performance of our model.

X-ray diffraction and nuclear magnetic resonance spectroscopy are the main methods for measuring membrane proteins. The traditional methods are time-consuming and labor-intensive. To large-scale prediction and screening of membrane proteins, a graph regularized k-local hyperplane distance nearest neighbor model (GHKNN) is proposed to identify of membrane protein types. For effectively integrating features, multi-view learning (MVL) is employed to estimate the weight of each graph. We test GHKNN on 2 data sets of membrane protein. Compared with other methods, the accuracy of GHKNN is better or comparable.

BACKGROUND: DNA-Binding Proteins (DBP) plays a pivotal role in biological system. A mounting number of researchers are studying the mechanism and detection methods. To detect DBP, the tradition experimental method is time-consuming and resource-consuming. In recent years, Machine Learning methods have been used to detect DBP. However, it is difficult to adequately describe the information of proteins in predicting DNA-binding proteins. In this study, we extract six features from protein sequence and use Multiple Kernel Learning-based on Centered Kernel Alignment to integrate these features. The integrated feature is fed into Support Vector Machine to build predictive model and detect new DBP. RESULTS: In our work, date sets of PDB1075 and PDB186 are employed to test our method. From the results, our model obtains better results (accuracy) than other existing methods on PDB1075 ([Formula: see text]) and PDB186 ([Formula: see text]), respectively. CONCLUSION: Multiple kernel learning could fuse the complementary information between different features. Compared with existing methods, our method achieves comparable and best results on benchmark data sets.

AADL (Architecture Analysis and Design Language) is widely used in the area of modeling and analysis. However, it is not so convenient to describe a hybrid system with AADL. In this paper, we propose an approach to construct an annex of AADL, thus to facilitate the modeling and analysis of hybrid system. The syntax and semantics of hybrid AADL are provided. Additionally, we developed a hybrid system modeling plug-in to OSATE, which is an AADL supporting tool. Our approach, as well as our tool, is successfully used in the development of a lunar rover control system for the institute of China Aerospace Science and Technology.