A Classification Supervised Auto-Encoder Based on Predefined Evenly-Distributed Class Centroids

Classic Autoencoders and variational autoencoders are used to learn complex data distributions, that are built on standard function approximators, such as neural networks, which can be trained by stochastic gradient descent methods. Especially, VAE has shown promise on a lot of complex task. In this paper, a new autoencoder model - classification supervised autoencoder (CSAE) based on predefined evenly-distributed class centroids (PEDCC) is proposed. To carry out the supervised learning for autoencoder, we use PEDCC of latent variables to train the network to ensure the maximization of inter-class distance and the minimization of inner-class distance. Instead of learning mean/variance of latent variables distribution and taking reparameterization of VAE, latent variables of CSAE are directly used to classify and as input of decoder. In addition, a new loss function is proposed to combine the loss function of classification, the loss function of image codec error and the loss function for enhancing subjective quality of decoded image. Based on the basic structure of the universal autoencoder, we realized the comprehensive optimal results of encoding, decoding and classification, and good model generalization performance at the same time. Theoretical advantages are reflected in experimental results.Comment: 17 pages,9 figures, 5 table

Discrimination of approved drugs from experimental drugs by learning methods

<p>Abstract</p> <p>Background</p> <p>To assess whether a compound is druglike or not as early as possible is always critical in drug discovery process. There have been many efforts made to create sets of 'rules' or 'filters' which, it is hoped, will help chemists to identify 'drug-like' molecules from 'non-drug' molecules. However, among the chemical space of the druglike molecules, the minority will be approved drugs. Classifying approved drugs from experimental drugs may be more helpful to obtain future approved drugs. Therefore, discrimination of approved drugs from experimental ones has been done in this paper by analyzing the compounds in terms of existing drugs features and machine learning methods.</p> <p>Results</p> <p>Four methodologies were compared by their performance to classify approved drugs from experimental ones. The best results were obtained by SVM, in which the accuracy is 0.7911, the sensitivity is 0.5929, and the specificity is 0.8743. Based on the results, consensus model was developed to effectively discriminate drugs, which further pushed the correct classification rate up to 0.8517, sensitivity up to 0.7242, specificity up to 0.9352. The applications on the Traditional Chinese Medicine Ingredients Database (TCM-ID) tested the methods. Therefore this model has been proven to be a potent tool for identifying drug molecules.</p> <p>Conclusion</p> <p>The studies would have potential applications in the research of combinatorial library design and virtual high throughput screening for drug discovery.</p

A new protein-ligand binding sites prediction method based on the integration of protein sequence conservation information

<p>Abstract</p> <p>Background</p> <p>Prediction of protein-ligand binding sites is an important issue for protein function annotation and structure-based drug design. Nowadays, although many computational methods for ligand-binding prediction have been developed, there is still a demanding to improve the prediction accuracy and efficiency. In addition, most of these methods are purely geometry-based, if the prediction methods improvement could be succeeded by integrating physicochemical or sequence properties of protein-ligand binding, it may also be more helpful to address the biological question in such studies.</p> <p>Results</p> <p>In our study, in order to investigate the contribution of sequence conservation in binding sites prediction and to make up the insufficiencies in purely geometry based methods, a simple yet efficient protein-binding sites prediction algorithm is presented, based on the geometry-based cavity identification integrated with sequence conservation information. Our method was compared with the other three classical tools: PocketPicker, SURFNET, and PASS, and evaluated on an existing comprehensive dataset of 210 non-redundant protein-ligand complexes. The results demonstrate that our approach correctly predicted the binding sites in 59% and 75% of cases among the TOP1 candidates and TOP3 candidates in the ranking list, respectively, which performs better than those of SURFNET and PASS, and achieves generally a slight better performance with PocketPicker.</p> <p>Conclusions</p> <p>Our work has successfully indicated the importance of the sequence conservation information in binding sites prediction as well as provided a more accurate way for binding sites identification.</p

Spatially Weighted Principal Component Analysis for Imaging Classification

The aim of this paper is to develop a supervised dimension reduction framework, called Spatially Weighted Principal Component Analysis (SWPCA), for high dimensional imaging classification. Two main challenges in imaging classification are the high dimensionality of the feature space and the complex spatial structure of imaging data. In SWPCA, we introduce two sets of novel weights including global and local spatial weights, which enable a selective treatment of individual features and incorporation of the spatial structure of imaging data and class label information. We develop an e cient two-stage iterative SWPCA algorithm and its penalized version along with the associated weight determination. We use both simulation studies and real data analysis to evaluate the finite-sample performance of our SWPCA. The results show that SWPCA outperforms several competing principal component analysis (PCA) methods, such as supervised PCA (SPCA), and other competing methods, such as sparse discriminant analysis (SDA)

Multi-target QSAR modelling in the analysis and design of HIV-HCV co-inhibitors: an in-silico study

<p>Abstract</p> <p>Background</p> <p>HIV and HCV infections have become the leading global public-health threats. Even more remarkable, HIV-HCV co-infection is rapidly emerging as a major cause of morbidity and mortality throughout the world, due to the common rapid mutation characteristics of the two viruses as well as their similar complex influence to immunology system. Although considerable progresses have been made on the study of the infection of HIV and HCV respectively, few researches have been conducted on the investigation of the molecular mechanism of their co-infection and designing of the multi-target co-inhibitors for the two viruses simultaneously.</p> <p>Results</p> <p>In our study, a multi-target Quantitative Structure-Activity Relationship (QSAR) study of the inhibitors for HIV-HCV co-infection were addressed with an in-silico machine learning technique, i.e. multi-task learning, to help to guide the co-inhibitor design. Firstly, an integrated dataset with 3 HIV inhibitor subsets targeted on protease, integrase and reverse transcriptase respectively, together with another 6 subsets of 2 HCV inhibitors targeted on NS3 serine protease and NS5B polymerase respectively were compiled. Secondly, an efficient multi-target QSAR modelling of HIV-HCV co-inhibitors was performed by applying an accelerated gradient method based multi-task learning on the whole 9 datasets. Furthermore, by solving the <it>L</it>-1-infinity regularized optimization, the Drug-like index features for compound description were ranked according to their joint importance in multi-target QSAR modelling of HIV and HCV. Finally, a drug structure-activity simulation for investigating the relationships between compound structures and binding affinities was presented based on our multiple target analysis, which is then providing several novel clues for the design of multi-target HIV-HCV co-inhibitors with increasing likelihood of successful therapies on HIV, HCV and HIV-HCV co-infection.</p> <p>Conclusions</p> <p>The framework presented in our study provided an efficient way to identify and design inhibitors that simultaneously and selectively bind to multiple targets from multiple viruses with high affinity, and will definitely shed new lights on the future work of inhibitor synthesis for multi-target HIV, HCV, and HIV-HCV co-infection treatments.</p