Lupus nephritis pathology prediction with clinical indices.

Effective treatment of lupus nephritis and assessment of patient prognosis depend on accurate pathological classification and careful use of acute and chronic pathological indices. Renal biopsy can provide most reliable predicting power. However, clinicians still need auxiliary tools under certain circumstances. Comprehensive statistical analysis of clinical indices may be an effective support and supplementation for biopsy. In this study, 173 patients with lupus nephritis were classified based on histology and scored on acute and chronic indices. These results were compared against machine learning predictions involving multilinear regression and random forest analysis. For three class random forest analysis, total classification accuracy was 51.3% (class II 53.7%, class III&IV 56.2%, class V 40.1%). For two class random forest analysis, class II accuracy reached 56.2%; class III&IV 63.7%; class V 61%. Additionally, machine learning selected out corresponding important variables for each class prediction. Multiple linear regression predicted the index of chronic pathology (CI) (Q2 = 0.746, R2 = 0.771) and the acute index (AI) (Q2 = 0.516, R2 = 0.576), and each variable's importance was calculated in AI and CI models. Evaluation of lupus nephritis by machine learning showed potential for assessment of lupus nephritis.

ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database.

Current pharmaceutical research and development (R&D) is a high-risk investment which is usually faced with some unexpected even disastrous failures in different stages of drug discovery. One main reason for R&D failures is the efficacy and safety deficiencies which are related largely to absorption, distribution, metabolism and excretion (ADME) properties and various toxicities (T). Therefore, rapid ADMET evaluation is urgently needed to minimize failures in the drug discovery process. Here, we developed a web-based platform called ADMETlab for systematic ADMET evaluation of chemicals based on a comprehensively collected ADMET database consisting of 288,967 entries. Four function modules in the platform enable users to conveniently perform six types of drug-likeness analysis (five rules and one prediction model), 31 ADMET endpoints prediction (basic property: 3, absorption: 6, distribution: 3, metabolism: 10, elimination: 2, toxicity: 7), systematic evaluation and database/similarity searching. We believe that this web platform will hopefully facilitate the drug discovery process by enabling early drug-likeness evaluation, rapid ADMET virtual screening or filtering and prioritization of chemical structures. The ADMETlab web platform is designed based on the Django framework in Python, and is freely accessible at http://admet.scbdd.com/ .

PyBioMed: a python library for various molecular representations of chemicals, proteins and DNAs and their interactions.

BACKGROUND: With the increasing development of biotechnology and informatics technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in these data needs to be extracted and transformed to useful knowledge by various data mining methods. Considering the amazing rate at which data are accumulated in chemistry and biology fields, new tools that process and interpret large and complex interaction data are increasingly important. So far, there are no suitable toolkits that can effectively link the chemical and biological space in view of molecular representation. To further explore these complex data, an integrated toolkit for various molecular representation is urgently needed which could be easily integrated with data mining algorithms to start a full data analysis pipeline. RESULTS: Herein, the python library PyBioMed is presented, which comprises functionalities for online download for various molecular objects by providing different IDs, the pretreatment of molecular structures, the computation of various molecular descriptors for chemicals, proteins, DNAs and their interactions. PyBioMed is a feature-rich and highly customized python library used for the characterization of various complex chemical and biological molecules and interaction samples. The current version of PyBioMed could calculate 775 chemical descriptors and 19 kinds of chemical fingerprints, 9920 protein descriptors based on protein sequences, more than 6000 DNA descriptors from nucleotide sequences, and interaction descriptors from pairwise samples using three different combining strategies. Several examples and five real-life applications were provided to clearly guide the users how to use PyBioMed as an integral part of data analysis projects. By using PyBioMed, users are able to start a full pipelining from getting molecular data, pretreating molecules, molecular representation to constructing machine learning models conveniently. CONCLUSION: PyBioMed provides various user-friendly and highly customized APIs to calculate various features of biological molecules and complex interaction samples conveniently, which aims at building integrated analysis pipelines from data acquisition, data checking, and descriptor calculation to modeling. PyBioMed is freely available at http://projects.scbdd.com/pybiomed.html .

Biopsy-Free Prediction of Pathologic Type of Primary Nephrotic Syndrome Using a Machine Learning Algorithm.

BACKGROUND/AIMS: Renal biopsy is the gold standard to determine the pathologic type of primary nephrotic syndrome, which is critical for diagnosis, choice of treatment and evaluation of prognosis. However, in some cases, renal biopsy cannot be performed. METHODS: To explore the possibility of predicting the histology type of primary nephrotic syndrome without the need for biopsy, we trained and validated a machine learning algorithm using data from 222 patients with biopsy-confirmed primary nephrotic syndrome treated at our hospital between May 2008 and January 2016. The model was then tested prospectively on another sample of 63 patients with biopsy-confirmed primary nephrotic syndrome. RESULTS: Overall accuracy of prediction from the retrospective set of 222 patients was 62.2% across all types of nephrotic syndrome. The accuracy of model prediction for the prospectively collected dataset of 63 patients was 61.9%. The algorithm identified 17 of 33 variables as contributing strongly to type of renal pathology. CONCLUSION: To our knowledge, this is the first such application of machine learning to predict the pathologic type of primary nephrotic syndrome, which may be clinically useful by itself as well as helpful for guiding future efforts at machine learning-based prediction in other disease contexts.

ChemSAR: an online pipelining platform for molecular SAR modeling.

BACKGROUND: In recent years, predictive models based on machine learning techniques have proven to be feasible and effective in drug discovery. However, to develop such a model, researchers usually have to combine multiple tools and undergo several different steps (e.g., RDKit or ChemoPy package for molecular descriptor calculation, ChemAxon Standardizer for structure preprocessing, scikit-learn package for model building, and ggplot2 package for statistical analysis and visualization, etc.). In addition, it may require strong programming skills to accomplish these jobs, which poses severe challenges for users without advanced training in computer programming. Therefore, an online pipelining platform that integrates a number of selected tools is a valuable and efficient solution that can meet the needs of related researchers. RESULTS: This work presents a web-based pipelining platform, called ChemSAR, for generating SAR classification models of small molecules. The capabilities of ChemSAR include the validation and standardization of chemical structure representation, the computation of 783 1D/2D molecular descriptors and ten types of widely-used fingerprints for small molecules, the filtering methods for feature selection, the generation of predictive models via a step-by-step job submission process, model interpretation in terms of feature importance and tree visualization, as well as a helpful report generation system. The results can be visualized as high-quality plots and downloaded as local files. CONCLUSION: ChemSAR provides an integrated web-based platform for generating SAR classification models that will benefit cheminformatics and other biomedical users. It is freely available at: http://chemsar.scbdd.com . Graphical abstract .

BioTriangle: a web-accessible platform for generating various molecular representations for chemicals, proteins, DNAs/RNAs and their interactions.

BACKGROUND: More and more evidences from network biology indicate that most cellular components exert their functions through interactions with other cellular components, such as proteins, DNAs, RNAs and small molecules. The rapidly increasing amount of publicly available data in biology and chemistry enables researchers to revisit interaction problems by systematic integration and analysis of heterogeneous data. Currently, some tools have been developed to represent these components. However, they have some limitations and only focus on the analysis of either small molecules or proteins or DNAs/RNAs. To the best of our knowledge, there is still a lack of freely-available, easy-to-use and integrated platforms for generating molecular descriptors of DNAs/RNAs, proteins, small molecules and their interactions. RESULTS: Herein, we developed a comprehensive molecular representation platform, called BioTriangle, to emphasize the integration of cheminformatics and bioinformatics into a molecular informatics platform for computational biology study. It contains a feature-rich toolkit used for the characterization of various biological molecules and complex interaction samples including chemicals, proteins, DNAs/RNAs and even their interactions. By using BioTriangle, users are able to start a full pipelining from getting molecular data, molecular representation to constructing machine learning models conveniently. CONCLUSION: BioTriangle provides a user-friendly interface to calculate various features of biological molecules and complex interaction samples conveniently. The computing tasks can be submitted and performed simply in a browser without any sophisticated installation and configuration process. BioTriangle is freely available at http://biotriangle.scbdd.com.Graphical abstractAn overview of BioTriangle. A platform for generating various molecular representations for chemicals, proteins, DNAs/RNAs and their interactions.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

ADME Properties Evaluation in Drug Discovery: Prediction of Caco-2 Cell Permeability Using a Combination of NSGA-II and Boosting.

The Caco-2 cell monolayer model is a popular surrogate in predicting the in vitro human intestinal permeability of a drug due to its morphological and functional similarity with human enterocytes. A quantitative structure-property relationship (QSPR) study was carried out to predict Caco-2 cell permeability of a large data set consisting of 1272 compounds. Four different methods including multivariate linear regression (MLR), partial least-squares (PLS), support vector machine (SVM) regression and Boosting were employed to build prediction models with 30 molecular descriptors selected by nondominated sorting genetic algorithm-II (NSGA-II). The best Boosting model was obtained finally with R(2) = 0.97, RMSEF = 0.12, Q(2) = 0.83, RMSECV = 0.31 for the training set and RT(2) = 0.81, RMSET = 0.31 for the test set. A series of validation methods were used to assess the robustness and predictive ability of our model according to the OECD principles and then define its applicability domain. Compared with the reported QSAR/QSPR models about Caco-2 cell permeability, our model exhibits certain advantage in database size and prediction accuracy to some extent. Finally, we found that the polar volume, the hydrogen bond donor, the surface area and some other descriptors can influence the Caco-2 permeability to some extent. These results suggest that the proposed model is a good tool for predicting the permeability of drug candidates and to perform virtual screening in the early stage of drug development.