Background In the search for therapeutic peptides for disease treatments, many efforts have been made to identify various functional peptides from large numbers of peptide sequence databases. In this paper, we propose an effective computational model that uses deep learning and word2vec to predict therapeutic peptides (PTPD). Results Representation vectors of all k-mers were obtained through word2vec based on k-mer co-existence information. The original peptide sequences were then divided into k-mers using the windowing method. The peptide sequences were mapped to the input layer by the embedding vector obtained by word2vec. Three types of filters in the convolutional layers, as well as dropout and max-pooling operations, were applied to construct feature maps. These feature maps were concatenated into a fully connected dense layer, and rectified linear units (ReLU) and dropout operations were included to avoid over-fitting of PTPD. The classification probabilities were generated by a sigmoid function. PTPD was then validated using two datasets: an independent anticancer peptide dataset and a virulent protein dataset, on which it achieved accuracies of 96% and 94%, respectively. Conclusions PTPD identified novel therapeutic peptides efficiently, and it is suitable for application as a useful tool in therapeutic peptide design.

Bacteriophage virion proteins and non-virion proteins have distinct functions in biological processes, such as specificity determination for host bacteria, bacteriophage replication and transcription. Accurate identification of bacteriophage virion proteins from bacteriophage protein sequences is significant to understand the complex virulence mechanism in host bacteria and the influence of bacteriophages on the development of antibacterial drugs. In this study, an ensemble method for bacteriophage virion protein prediction from bacteriophage protein sequences is put forward with hybrid feature spaces incorporating CTD (composition, transition and distribution), bi-profile Bayes, PseAAC (pseudo-amino acid composition) and PSSM (position-specific scoring matrix). When performing on the training dataset 10-fold cross-validation, the presented method achieves a satisfactory prediction result with a sensitivity of 0.870, a specificity of 0.830, an accuracy of 0.850 and Matthew’s correlation coefficient (MCC) of 0.701, respectively. To evaluate the prediction performance objectively, an independent testing dataset is used to evaluate the proposed method. Encouragingly, our proposed method performs better than previous studies with a sensitivity of 0.853, a specificity of 0.815, an accuracy of 0.831 and MCC of 0.662 on the independent testing dataset. These results suggest that the proposed method can be a potential candidate for bacteriophage virion protein prediction, which may provide a useful tool to find novel antibacterial drugs and to understand the relationship between bacteriophage and host bacteria. For the convenience of the vast majority of experimental Int. J. Mol. Sci. 2015, 16 21735 scientists, a user-friendly and publicly-accessible web-server for the proposed ensemble method is established.

Background: Aptamer-protein interacting pairs play a variety of physiological functions and therapeutic potentials in organisms. Rapidly and effectively predicting aptamer-protein interacting pairs is significant to design aptamers binding to certain interested proteins, which will give insight into understanding mechanisms of aptamer-protein interacting pairs and developing aptamer-based therapies. Results: In this study, an ensemble method is presented to predict aptamer-protein interacting pairs with hybrid features. The features for aptamers are extracted from Pseudo K-tuple Nucleotide Composition (PseKNC) while the features for proteins incorporate Discrete Cosine Transformation (DCT), disorder information, and bi-gram Position Specific Scoring Matrix (PSSM). We investigate predictive capabilities of various feature spaces. The proposed ensemble method obtains the best performance with Youden’s Index of 0.380, using the hybrid feature space of PseKNC, DCT, bi-gram PSSM, and disorder information by 10-fold cross validation. The Relief-Incremental Feature Selection (IFS) method is adopted to obtain the optimal feature set. Based on the optimal feature set, the proposed method achieves a balanced performance with a sensitivity of 0.753 and a specificity of 0.725 on the training dataset, which indicates that this method can solve the imbalanced data problem effectively. To evaluate the prediction performance objectively, an independent testing dataset is used to evaluate the proposed method. Encouragingly, our proposed method performs better than previous study with a sensitivity of 0.738 and a Youden’s Index of 0.451. Conclusions: These results suggest that the proposed method can be a potential candidate for aptamer-protein interacting pair prediction, which may contribute to finding novel aptamer-protein interacting pairs and understanding the relationship between aptamers and proteins.

Microorganisms resided in human body play a vital role in metabolism, immune defense, nutrition absorption, cancer control and protection against pathogen colonization. The changes of microbial communities can cause human diseases. Based on the known microbe-disease association, we presented a novel computational model employing Random Walking with Restart optimized by Particle Swarm Optimization (PSO) on the heterogeneous interlinked network of Human Microbe-Disease Associations (PRWHMDA) (see Figure 1). Based on the known human microbe-disease associations, we constructed the heterogeneous interlinked network with Cosine similarity. The extended random walk with restart (RWR) method was derived to get the potential microbe-disease associations. PSO was utilized to get the optimal parameters of RWR. To evaluate the prediction effectiveness, we performed leave one out cross validation (LOOCV) and 5-fold cross validation (CV), which got the AUC (The area under ROC curve) of 0.915 (LOOCV) and the average AUCs of 0.8875 ± 0.0046 (5-fold CV). Moreover, we carried out three case studies of asthma, inflammatory bowel disease (IBD) and type 1 diabetes (T1D) for the further evaluation. The result showed that 10, 10 and 9 of top-10 predicted microbes were verified by previously published experimental results, respectively. It is anticipated that PRWHMDA can be effective to identify the disease-related microbes and maybe helpful to disclose the relationship between microorganisms and their human host.

The Golgi Apparatus (GA) is a major collection and dispatch station for numerous proteins destined for secretion, plasma membranes and lysosomes. The dysfunction of GA proteins can result in neurodegenerative diseases. Therefore, accurate identification of protein subGolgi localizations may assist in drug development and understanding the mechanisms of the GA involved in various cellular processes. In this paper, a new computational method is proposed for identifying cis-Golgi proteins from trans-Golgi proteins. Based on the concept of Common Spatial Patterns (CSP), a novel feature extraction technique is developed to extract evolutionary information from protein sequences. To deal with the imbalanced benchmark dataset, the Synthetic Minority Over-sampling Technique (SMOTE) is adopted. A feature selection method called Random Forest-Recursive Feature Elimination (RF-RFE) is employed to search the optimal features from the CSP based features and g-gap dipeptide composition. Based on the optimal features, a Random Forest (RF) module is used to distinguish cis-Golgi proteins from trans-Golgi proteins. Through the jackknife cross-validation, the proposed method achieves a promising performance with a sensitivity of 0.889, a specificity of 0.880, an accuracy of 0.885, and a Matthew’s Correlation Coefficient (MCC) of 0.765, which remarkably outperforms previous methods. Moreover, when tested on a common independent dataset, our method also achieves a significantly improved performance. These results highlight the promising performance of the proposed method to identify Golgi-resident protein types. Furthermore, the CSP based feature extraction method may provide guidelines for protein function predictions.

Cardiovascular systems essentially have multiscale control mechanisms. Multiscale entropy (MSE) analysis permits the dynamic characterization of the cardiovascular time series for both short-term and long-term processes, and thus can be more illuminating. The traditional MSE analysis for heart rate variability (HRV) is performed on the original RR interval time series (named as MSE_RR). In this study, we proposed an MSE analysis for the differential RR interval time series signal, named as MSE_dRR. The motivation of using the differential RR interval time series signal is that this signal has a direct link with the inherent non-linear property of electrical rhythm of the heart. The effectiveness of the MSE_RR and MSE_dRR were tested and compared on the long-term MIT-Boston’s Beth Israel Hospital (MIT-BIH) 54 normal sinus rhythm (NSR) and 29 congestive heart failure (CHF) RR interval recordings, aiming to explore which one is better for distinguishing the CHF patients from the NSR subjects. Four RR interval length for analysis were used ( $N=500,N=1000$ , $N=2000$ and $N=5000$ ). The results showed that MSE_RR did not report significant differences between the NSR and CHF groups at several scales for each RR segment length type (Scales 7, 8 and 10 for $N=500$ , Scales 3 and 10 for $N=1000$ , Scales 2 and 3 for both $N=2000$ and $N=5000$ ). However, the new MSE_dRR gave significant separation for the two groups for all RR segment length types except $N=500$ at Scales 9 and 10. The area under curve (AUC) values from the receiver operating characteristic (ROC) curve were used to further quantify the performances. The mean AUC of the new MSE_dRR from Scales 1–10 are 79.5%, 83.1%, 83.5% and 83.1% for $N=500$ , $N=1000$ , $N=2000$ and $N=5000$ , respectively, whereas the mean AUC of MSE_RR are only 68.6%, 69.8%, 69.6% and 67.1%, respectively. The five-fold cross validation support vector machine (SVM) classifier reports the classification Accuracy ( $Acc$ ) of MSE_RR as 73.5%, 75.9% and 74.6% for $N=1000$ , $N=2000$ and $N=5000$ , respectively, while for the new MSE_dRR analysis accuracy was 85.5%, 85.6% and 85.6%. Different biosignal editing methods (direct deletion and interpolation) did not change the analytical results. In summary, this study demonstrated that compared with MSE_RR, MSE_dRR reports better statistical stability and better discrimination ability for the NSR and CHF groups.