In this work, we improved a previous model used for the prediction of proteomes as new B-cell epitopes in vaccine design. The predicted epitope activity of a queried peptide is based on its sequence, ...a known reference epitope sequence under specific experimental conditions. The peptide sequences were transformed into molecular descriptors of sequence recurrence networks and were mixed under experimental conditions. The new models were generated using 709,100 instances of pair descriptors for query and reference peptide sequences. Using perturbations of the initial descriptors under sequence or assay conditions, 10 transformed features were used as inputs for seven Machine Learning methods. The best model was obtained with random forest classifiers with an Area Under the Receiver Operating Characteristics (AUROC) of 0.981 ± 0.0005 for the external validation series (five-fold cross-validation). The database included information about 83,683 peptides sequences, 1448 epitope organisms, 323 host organisms, 15 types of in vivo processes, 28 experimental techniques, and 505 adjuvant additives. The current model could improve the in silico predictions of epitopes for vaccine design. The script and results are available as a free repository.
Reducing costs in terms of time, animal sacrifice, and material resources with computational methods has become a promising goal in Medicinal, Biological, Physical and Organic Chemistry. There are ...many computational techniques that can be used in this sense. In any case, almost all these methods focus on few fundamental aspects including: type (1) methods to quantify the molecular structure, type (2) methods to link the structure with the biological activity, and others. In particular, MARCH-INSIDE (MI), acronym for Markov Chain Invariants for Networks Simulation and Design, is a well-known method for QSAR analysis useful in step (1). In addition, the bio-inspired Artificial-Intelligence (AI) algorithms called Artificial Neural Networks (ANNs) are among the most powerful type (2) methods. We can combine MI with ANNs in order to seek QSAR models, a strategy which is called herein MIANN (MI & ANN models). One of the first applications of the MIANN strategy was in the development of new QSAR models for drug discovery. MIANN strategy has been expanded to the QSAR study of proteins, protein-drug interactions, and protein-protein interaction networks. In this paper, we review for the first time many interesting aspects of the MIANN strategy including theoretical basis, implementation in web servers, and examples of applications in Medicinal and Biological chemistry. We also report new applications of the MIANN strategy in Medicinal chemistry and the first examples in Physical and Organic Chemistry, as well. In so doing, we developed new MIANN models for several self-assembly physicochemical properties of surfactants and large reaction networks in organic synthesis. In some of the new examples we also present experimental results which were not published up to date.
The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find ...prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.
Drug-decorated nanoparticles (DDNPs) have important medical applications. The current work combined Perturbation Theory with Machine Learning and Information Fusion (PTMLIF). Thus, PTMLIF models were ...proposed to predict the probability of nanoparticle–compound/drug complexes having antimalarial activity (against Plasmodium). The aim is to save experimental resources and time by using a virtual screening for DDNPs. The raw data was obtained by the fusion of experimental data for nanoparticles with compound chemical assays from the ChEMBL database. The inputs for the eight Machine Learning classifiers were transformed features of drugs/compounds and nanoparticles as perturbations of molecular descriptors in specific experimental conditions (experiment-centered features). The resulting dataset contains 107 input features and 249,992 examples. The best classification model was provided by Random Forest, with 27 selected features of drugs/compounds and nanoparticles in all experimental conditions considered. The high performance of the model was demonstrated by the mean Area Under the Receiver Operating Characteristics (AUC) in a test subset with a value of 0.9921 ± 0.000244 (10-fold cross-validation). The results demonstrated the power of information fusion of the experimental-centered features of drugs/compounds and nanoparticles for the prediction of nanoparticle–compound antimalarial activity. The scripts and dataset for this project are available in the open GitHub repository.
Consensus strategy was proved to be highly efficient in the recognition of gene-disease association. Therefore, the main objective of this study was to apply theoretical approaches to explore genes ...and communities directly involved in breast cancer (BC) pathogenesis. We evaluated the consensus between 8 prioritization strategies for the early recognition of pathogenic genes. A communality analysis in the protein-protein interaction (PPi) network of previously selected genes was enriched with gene ontology, metabolic pathways, as well as oncogenomics validation with the OncoPPi and DRIVE projects. The consensus genes were rationally filtered to 1842 genes. The communality analysis showed an enrichment of 14 communities specially connected with ERBB, PI3K-AKT, mTOR, FOXO, p53, HIF-1, VEGF, MAPK and prolactin signaling pathways. Genes with highest ranking were TP53, ESR1, BRCA2, BRCA1 and ERBB2. Genes with highest connectivity degree were TP53, AKT1, SRC, CREBBP and EP300. The connectivity degree allowed to establish a significant correlation between the OncoPPi network and our BC integrated network conformed by 51 genes and 62 PPi. In addition, CCND1, RAD51, CDC42, YAP1 and RPA1 were functional genes with significant sensitivity score in BC cell lines. In conclusion, the consensus strategy identifies both well-known pathogenic genes and prioritized genes that need to be further explored.
Osteosarcoma is the most common type of primary malignant bone tumor. Although nowadays 5-year survival rates can reach up to 60–70%, acute complications and late effects of osteosarcoma therapy are ...two of the limiting factors in treatments. We developed a multi-objective algorithm for the repurposing of new anti-osteosarcoma drugs, based on the modeling of molecules with described activity for HOS, MG63, SAOS2, and U2OS cell lines in the ChEMBL database. Several predictive models were obtained for each cell line and those with accuracy greater than 0.8 were integrated into a desirability function for the final multi-objective model. An exhaustive exploration of model combinations was carried out to obtain the best multi-objective model in virtual screening. For the top 1% of the screened list, the final model showed a BEDROC = 0.562, EF = 27.6, and AUC = 0.653. The repositioning was performed on 2218 molecules described in DrugBank. Within the top-ranked drugs, we found: temsirolimus, paclitaxel, sirolimus, everolimus, and cabazitaxel, which are antineoplastic drugs described in clinical trials for cancer in general. Interestingly, we found several broad-spectrum antibiotics and antiretroviral agents. This powerful model predicts several drugs that should be studied in depth to find new chemotherapy regimens and to propose new strategies for osteosarcoma treatment.
Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to ...predict HS for protein–protein and protein–nucleic acid interactions with better statistics compared with the ones currently reported in literature. These models are based on solvent accessible surface area (SASA) and genetic conservation features subjected to simple Bayes networks (protein–protein systems) and a more complex multi-objective genetic algorithm–support vector machine algorithms (protein–nucleic acid systems). The best models for these interactions have been implemented in two free Web tools.
•Experimental study and prediction model of microbiome cell surface hydrophobicity.•Expected Measurement Moving Average – Machine Learning model to predict CSH.•Random Forest prediction model with 12 ...features and test R-squared of 0.992.
The cell surface hydrophobicity (CSH) is an assessable physicochemical property used to evaluate the microbial adhesion to the surface of biomaterials, which is an essential step in the microbial biofilm formation and pathogenesis. For the present in vitro fermentation experiment, the CSH of ruminal mixed microbes was considered, along with other data records of pH, ammonia-nitrogen concentration, and neutral detergent fibre digestibility, conditions of surface tension and specific surface area in two different time scales. A dataset of 170,707 perturbations of input variables, grouped into two blocks of data, was constructed. Next, Expected Measurement Moving Average – Machine Learning (EMMA-ML) models were developed in order to predict CSH after perturbations of all input variables. EMMA-ML is a Perturbation Theory method that combines the ideas of Expected Measurement, Box-Jenkins Operators/Moving Average, and Time Series Analysis. Seven regression methods have been tested: Multiple Linear regression, Generalized Linear Model with Stepwise Feature Selection, Partial Least Squares regression, Lasso regression, Elastic Net regression, Neural Networks regression, and Random Forests (RF). The best regression performance has been obtained with RF (EMMA-RF model) with an R-squared of 0.992. The model analysis has shown that CSH values were highly dependent on the in vitro fermentation parameters of detergent fibre digestibility, ammonia – nitrogen concentration, and the expected values of cell surface hydrophobicity in the first time scale.
This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this ...methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.
Schizophrenia is a complex disease, with both genetic and environmental influence. Machine learning techniques can be used to associate different genetic variations at different genes with a ...(schizophrenic or non-schizophrenic) phenotype. Several machine learning techniques were applied to schizophrenia data to obtain the results presented in this study. Considering these data, Quantitative Genotype - Disease Relationships (QDGRs) can be used for disease prediction. One of the best machine learning-based models obtained after this exhaustive comparative study was implemented online; this model is an artificial neural network (ANN). Thus, the tool offers the possibility to introduce Single Nucleotide Polymorphism (SNP) sequences in order to classify a patient with schizophrenia. Besides this comparative study, a method for variable selection, based on ANNs and evolutionary computation (EC), is also presented. This method uses half the number of variables as the original ANN and the variables obtained are among those found in other publications. In the future, QDGR models based on nucleic acid information could be expanded to other diseases.
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