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Cell-penetrating peptides (CPPs) are special peptides capable of carrying a variety of bioactive molecules, such as genetic materials, short interfering RNAs and nanoparticles, into cells. Recently, research on CPP has gained substantial interest from researchers, and the biological mechanisms of CPPS have been assessed in the context of safe drug delivery agents and therapeutic applications. Correct identification and synthesis of CPPs using traditional biochemical methods is an extremely slow, expensive and laborious task particularly due to the large volume of unannotated peptide sequences accumulating in the World Bank repository. Hence, a powerful bioinformatics predictor that rapidly identifies CPPs with a high recognition rate is urgently needed. To date, numerous computational methods have been developed for CPP prediction. However, the available machine-learning (ML) tools are unable to distinguish both the CPPs and their uptake efficiencies. This study aimed to develop a two-layer deep learning framework named DeepCPPred to identify both CPPs in the first phase and peptide uptake efficiency in the second phase. The DeepCPPred predictor first uses four types of descriptors that cover evolutionary, energy estimation, reduced sequence and amino-acid contact information. Then, the extracted features are optimized through the elastic net algorithm and fed into a cascade deep forest algorithm to build the final CPP model. The proposed method achieved 99.45 percent overall accuracy with the CPP924 benchmark dataset in the first layer and 95.43 percent accuracy in the second layer with the CPPSite3 dataset using a 5-fold cross-validation test. Thus, our proposed bioinformatics tool surpassed all the existing state-of-the-art sequence-based CPP approaches. [ABSTRACT FROM AUTHOR]

Accurate short-term traffic flow prediction plays an important role in the field of modern Intelligent Transportation Systems. Since various uncontrollable factors (e.g. weather, traffic jams or accidents), collected traffic data inevitably contain outliers. This makes it challenge to achieve satisfactory results for traffic flow prediction. Least Squares Twin Support Vector Regression (LSTSVR) has been shown to provide a powerful potential in nonlinear prediction problems. This is especially true when using appropriate heuristic algorithms to determine the parameters of nonlinear LSTSVR. In view of this, a novel LSTSVR model based on the robust $\text{L}_{2,\mathrm {p}}$ -norm ($0< p\le 2$) distance is proposed to alleviate the negative effect of traffic data with outliers, called PLSTSVR. An iterative algorithm is designed to solve the optimization problem of PLSTSVR, which has great potential for solving other relevant optimization problems. To search the parameters of constructed PLSTSVR, this paper constructs two traffic flow prediction models based on PLSTSVR and heuristic algorithms (Fruit Fly Optimization Algorithm and Particle Swarm Optimization), called PLSTSVR-FOA and PLSTSVR-PSO. Extensive experiments demonstrate that the constructed models are more effective and robust than other competing models in various experimental settings. [ABSTRACT FROM AUTHOR]

Accurately identifying DNA-binding proteins (DBPs) from protein sequence information is an important but challenging task for protein function annotations. In this paper, we establish a novel computational method, named TargetDBP, for accurately targeting DBPs from primary sequences. In TargetDBP, four single-view features, i.e., AAC (Amino Acid Composition), PsePSSM (Pseudo Position-Specific Scoring Matrix), PsePRSA (Pseudo Predicted Relative Solvent Accessibility), and PsePPDBS (Pseudo Predicted Probabilities of DNA-Binding Sites), are first extracted to represent different base features, respectively. Second, differential evolution algorithm is employed to learn the weights of four base features. Using the learned weights, we weightedly combine these base features to form the original super feature. An excellent subset of the super feature is then selected by using a suitable feature selection algorithm SVM-REF+CBR (Support Vector Machine Recursive Feature Elimination with Correlation Bias Reduction). Finally, the prediction model is learned via using support vector machine on the selected feature subset. We also construct a new gold-standard and non-redundant benchmark dataset from PDB database to evaluate and compare the proposed TargetDBP with other existing predictors. On this new dataset, TargetDBP can achieve higher performance than other state-of-the-art predictors. The TargetDBP web server and datasets are freely available at http://csbio.njust.edu.cn/bioinf/targetdbp/ for academic use. [ABSTRACT FROM AUTHOR]

Active learning algorithms attempt to overcome the labeling bottleneck by asking queries from large collection of unlabeled examples. Existing batch mode active learning algorithms suffer from three limitations: (1) The methods that are based on similarity function or optimizing certain diversity measurement, in which may lead to suboptimal performance and produce the selected set with redundant examples. (2) The models with assumption on data are hard in finding images that are both informative and representative. (3) The problem of noise labels has been an obstacle for algorithms. In this paper, we propose a novel active learning method that makes embeddings of labeled examples to those of unlabeled ones and back via deep neural networks. The active scheme makes correct association cycles that end up at the same class from that the association was started, which considers both the informativeness and representativeness of examples, as well as being robust to the noise labels. We apply our active learning method to semi-supervised classification and clustering. The submodular function is designed to reduce the redundancy of the selected examples. Specifically, we incorporate our batch mode active scheme into the classification approaches, in which the generalization ability is improved. For semi-supervised clustering, we try to use our active scheme for constraints to make fast convergence and perform better than unsupervised clustering. Finally, we apply our active learning method to data filtering. To validate the effectiveness of the proposed algorithms, extensive experiments are conducted on diversity benchmark datasets for different tasks, i.e., classification, clustering, and data filtering, and the experimental results demonstrate consistent and substantial improvements over the state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

Accurate identification of the cancer types is essential to cancer diagnoses and treatments. Since cancer tissue and normal tissue have different gene expression, gene expression data can be used as an efficient feature source for cancer classification. However, accurate cancer classification directly using original gene expression profiles remains challenging due to the intrinsic high-dimension feature and the small size of the data samples. We proposed a new self-training subspace clustering algorithm under low-rank representation, called SSC-LRR, for cancer classification on gene expression data. Low-rank representation (LRR) is first applied to extract discriminative features from the high-dimensional gene expression data; the self-training subspace clustering (SSC) method is then used to generate the cancer classification predictions. The SSC-LRR was tested on two separate benchmark datasets in control with four state-of-the-art classification methods. It generated cancer classification predictions with an overall accuracy 89.7 percent and a general correlation 0.920, which are 18.9 and 24.4 percent higher than that of the best control method respectively. In addition, several genes (RNF114, HLA-DRB5, USP9Y, and PTPN20) were identified by SSC-LRR as new cancer identifiers that deserve further clinical investigation. Overall, the study demonstrated a new sensitive avenue to recognize cancer classifications from large-scale gene expression data. [ABSTRACT FROM AUTHOR]

Protein-DNA interactions are ubiquitous in a wide variety of biological processes. Correctly locating DNA-binding residues solely from protein sequences is an important but challenging task for protein function annotations and drug discovery, especially in the post-genomic era where large volumes of protein sequences have quickly accumulated. In this study, we report a new predictor, named TargetDNA, for targeting protein-DNA binding residues from primary sequences. TargetDNA uses a protein's evolutionary information and its predicted solvent accessibility as two base features and employs a centered linear kernel alignment algorithm to learn the weights for weightedly combining the two features. Based on the weightedly combined feature, multiple initial predictors with SVM as classifiers are trained by applying a random under-sampling technique to the original dataset, the purpose of which is to cope with the severe imbalance phenomenon that exists between the number of DNA-binding and non-binding residues. The final ensembled predictor is obtained by boosting the multiple initially trained predictors. Experimental simulation results demonstrate that the proposed TargetDNA achieves a high prediction performance and outperforms many existing sequence-based protein-DNA binding residue predictors. The TargetDNA web server and datasets are freely available at http://csbio.njust.edu.cn/bioinf/TargetDNA/ for academic use. [ABSTRACT FROM PUBLISHER]

As one of the most ubiquitous post-transcriptional modifications of RNA, N6-methyladenosine ( \text m^6\text A ) plays an essential role in many vital biological processes. The identification of \text m^6\text A sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target \text m^6\text A sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting \text m^6\text A sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting \text m^6\text A sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A. [ABSTRACT FROM PUBLISHER]

Protein-protein interactions exist ubiquitously and play important roles in the life cycles of living cells. The interaction sites (residues) are essential to understanding the underlying mechanisms of protein-protein interactions. Previous research has demonstrated that the accurate identification of protein-protein interaction sites (PPIs) is helpful for developing new therapeutic drugs because many drugs will interact directly with those residues. Because of its significant potential in biological research and drug development, the prediction of PPIs has become an important topic in computational biology. However, a severe data imbalance exists in the PPIs prediction problem, where the number of the majority class samples (non-interacting residues) is far larger than that of the minority class samples (interacting residues). Thus, we developed a novel cascade random forests algorithm (CRF) to address the serious data imbalance that exists in the PPIs prediction problem. The proposed CRF resolves the negative effect of data imbalance by connecting multiple random forests in a cascade-like manner, each of which is trained with a balanced training subset that includes all minority samples and a subset of majority samples using an effective ensemble protocol. Based on the proposed CRF, we implemented a new sequence-based PPIs predictor, called CRF-PPI, which takes the combined features of position-specific scoring matrices, averaged cumulative hydropathy, and predicted relative solvent accessibility as model inputs. Benchmark experiments on both the cross validation and independent validation datasets demonstrated that the proposed CRF-PPI outperformed the state-of-the-art sequence-based PPIs predictors. The source code for CRF-PPI and the benchmark datasets are available online at http://csbio.njust.edu.cn/bioinf/CRF-PPI for free academic use. [ABSTRACT FROM PUBLISHER]

Disulfide connectivity is an important protein structural characteristic. Accurately predicting disulfide connectivity solely from protein sequence helps to improve the intrinsic understanding of protein structure and function, especially in the post-genome era where large volume of sequenced proteins without being functional annotated is quickly accumulated. In this study, a new feature extracted from the predicted protein 3D structural information is proposed and integrated with traditional features to form discriminative features. Based on the extracted features, a random forest regression model is performed to predict protein disulfide connectivity. We compare the proposed method with popular existing predictors by performing both cross-validation and independent validation tests on benchmark datasets. The experimental results demonstrate the superiority of the proposed method over existing predictors. We believe the superiority of the proposed method benefits from both the good discriminative capability of the newly developed features and the powerful modelling capability of the random forest. The web server implementation, called TargetDisulfide, and the benchmark datasets are freely available at: http://csbio.njust.edu.cn/bioinf/TargetDisulfide for academic use. [ABSTRACT FROM PUBLISHER]

We are facing an era with annotated biological data rapidly and continuously generated. How to effectively incorporate new annotated data into the learning step is crucial for enhancing the performance of a bioinformatics prediction model. Although machine-learning-based methods have been extensively used for dealing with various biological problems, existing approaches usually train static prediction models based on fixed training datasets. The static approaches are found having several disadvantages such as low scalability and impractical when training dataset is huge. In view of this, we propose a dynamic learning framework for constructing query-driven prediction models. The key difference between the proposed framework and the existing approaches is that the training set for the machine learning algorithm of the proposed framework is dynamically generated according to the query input, as opposed to training a general model regardless of queries in traditional static methods. Accordingly, a query-driven predictor based on the smaller set of data specifically selected from the entire annotated base dataset will be applied on the query. The new way for constructing the dynamic model enables us capable of updating the annotated base dataset flexibly and using the most relevant core subset as the training set makes the constructed model having better generalization ability on the query, showing “part could be better than all” phenomenon. According to the new framework, we have implemented a dynamic protein-ligand binding sites predictor called OSML (On-site model for ligand binding sites prediction). Computer experiments on 10 different ligand types of three hierarchically organized levels show that OSML outperforms most existing predictors. The results indicate that the current dynamic framework is a promising future direction for bridging the gap between the rapidly accumulated annotated biological data and the effective machine-learning-based predictors. OSML web server and datasets are freely available at: http://www.csbio.sjtu.edu.cn/bioinf/OSML/ for academic use. [ABSTRACT FROM PUBLISHER]

Accurately identifying the protein-ligand binding sites or pockets is of significant importance for both protein function analysis and drug design. Although much progress has been made, challenges remain, especially when the 3D structures of target proteins are not available or no homology templates can be found in the library, where the template-based methods are hard to be applied. In this paper, we report a new ligand-specific template-free predictor called TargetS for targeting protein-ligand binding sites from primary sequences. TargetS first predicts the binding residues along the sequence with ligand-specific strategy and then further identifies the binding sites from the predicted binding residues through a recursive spatial clustering algorithm. Protein evolutionary information, predicted protein secondary structure, and ligand-specific binding propensities of residues are combined to construct discriminative features; an improved AdaBoost classifier ensemble scheme based on random undersampling is proposed to deal with the serious imbalance problem between positive (binding) and negative (nonbinding) samples. Experimental results demonstrate that TargetS achieves high performances and outperforms many existing predictors. TargetS web server and data sets are freely available at: http://www.csbio.sjtu.edu.cn/bioinf/TargetS/ for academic use. [ABSTRACT FROM PUBLISHER]