In recent years, ontologies have become a mainstream topic in biomedical research. When biological entities are described using a common schema, such as an ontology, they can be compared by means of their annotations. This type of comparison is called semantic similarity, since it assesses the degree of relatedness between two entities by the similarity in meaning of their annotations. The application of semantic similarity to biomedical ontologies is recent; nevertheless, several studies have been published in the last few years describing and evaluating diverse approaches. Semantic similarity has become a valuable tool for validating the results drawn from biomedical studies such as gene clustering, gene expression data analysis, prediction and validation of molecular interactions, and disease gene prioritization.We review semantic similarity measures applied to biomedical ontologies and propose their classification according to the strategies they employ: node-based versus edge-based and pairwise versus groupwise. We also present comparative assessment studies and discuss the implications of their results. We survey the existing implementations of semantic similarity measures, and we describe examples of applications to biomedical research. This will clarify how biomedical researchers can benefit from semantic similarity measures and help them choose the approach most suitable for their studies.Biomedical ontologies are evolving toward increased coverage, formality, and integration, and their use for annotation is increasingly becoming a focus of both effort by biomedical experts and application of automated annotation procedures to create corpora of higher quality and completeness than are currently available. Given that semantic similarity measures are directly dependent on these evolutions, we can expect to see them gaining more relevance and even becoming as essential as sequence similarity is today in biomedical research.

Background: Several semantic similarity measures have been applied to gene products annotated with Gene Ontology terms, providing a basis for their functional comparison. However, it is still unclear which is the best approach to semantic similarity in this context, since there is no conclusive evaluation of the various measures. Another issue, is whether electronic annotations should or not be used in semantic similarity calculations.

The human blood-brain barrier (BBB) is a membrane that protects the central nervous system (CNS) by restricting the passage of solutes. The development of any new drug must take into account its existence whether for designing new molecules that target components of the CNS or, on the other hand, to find new substances that should not penetrate the barrier. Several studies in the literature have attempted to predict BBB penetration, so far with limited success and few, if any, application to real world drug discovery and development programs. Part of the reason is due to the fact that only about 2% of small molecules can cross the BBB, and the available data sets are not representative of that reality, being generally biased with an over-representation of molecules that show an ability to permeate the BBB (BBB positives). To circumvent this limitation, the current study aims to devise and use a new approach based on Bayesian statistics, coupled with state-of-the-art machine learning methods to produce a robust model capable of being applied in real-world drug research scenarios. The data set used, gathered from the literature, totals 1970 curated molecules, one of the largest for similar studies. Random Forests and Support Vector Machines were tested in various configurations against several chemical descriptor set combinations. Models were tested in a 5-fold cross-validation process, and the best one tested over an independent validation set. The best fitted model produced an overall accuracy of 95%, with a mean square contingency coefficient (ϕ) of 0.74, and showing an overall capacity for predicting BBB positives of 83% and 96% for determining BBB negatives. This model was adapted into a Web based tool made available for the whole community at http://b3pp.lasige.di.fc.ul.pt.

BackgroundIn-silico quantitative structure–activity relationship (QSAR) models based tools are widely used to screen huge databases of compounds in order to determine the biological properties of chemical molecules based on their chemical structure. With the passage of time, the exponentially growing amount of synthesized and known chemicals data demands computationally efficient automated QSAR modeling tools, available to researchers that may lack extensive knowledge of machine learning modeling. Thus, a fully automated and advanced modeling platform can be an important addition to the QSAR community.ResultsIn the presented workflow the process from data preparation to model building and validation has been completely automated. The most critical modeling tasks (data curation, data set characteristics evaluation, variable selection and validation) that largely influence the performance of QSAR models were focused. It is also included the ability to quickly evaluate the feasibility of a given data set to be modeled. The developed framework is tested on data sets of thirty different problems. The best-optimized feature selection methodology in the developed workflow is able to remove 62–99% of all redundant data. On average, about 19% of the prediction error was reduced by using feature selection producing an increase of 49% in the percentage of variance explained (PVE) compared to models without feature selection. Selecting only the models with a modelability score above 0.6, average PVE scores were 0.71. A strong correlation was verified between the modelability scores and the PVE of the models produced with variable selection.ConclusionsWe developed an extendable and highly customizable fully automated QSAR modeling framework. This designed workflow does not require any advanced parameterization nor depends on users decisions or expertise in machine learning/programming. With just a given target or problem, the workflow follows an unbiased standard protocol to develop reliable QSAR models by directly accessing online manually curated databases or by using private data sets. The other distinctive features of the workflow include prior estimation of data modelability to avoid time-consuming modeling trials for non modelable data sets, an efficient variable selection procedure and the facility of output availability at each modeling task for the diverse application and reproduction of historical predictions. The results reached on a selection of thirty QSAR problems suggest that the approach is capable of building reliable models even for challenging problems.Electronic supplementary materialThe online version of this article (10.1186/s13321-017-0256-5) contains supplementary material, which is available to authorized users.

Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

BackgroundOne of the main topics in the development of quantitative structure-property relationship (QSPR) predictive models is the identification of the subset of variables that represent the structure of a molecule and which are predictors for a given property. There are several automated feature selection methods, ranging from backward, forward or stepwise procedures, to further elaborated methodologies such as evolutionary programming. The problem lies in selecting the minimum subset of descriptors that can predict a certain property with a good performance, computationally efficient and in a more robust way, since the presence of irrelevant or redundant features can cause poor generalization capacity. In this paper an alternative selection method, based on Random Forests to determine the variable importance is proposed in the context of QSPR regression problems, with an application to a manually curated dataset for predicting standard enthalpy of formation. The subsequent predictive models are trained with support vector machines introducing the variables sequentially from a ranked list based on the variable importance.ResultsThe model generalizes well even with a high dimensional dataset and in the presence of highly correlated variables. The feature selection step was shown to yield lower prediction errors with RMSE values 23% lower than without feature selection, albeit using only 6% of the total number of variables (89 from the original 1485). The proposed approach further compared favourably with other feature selection methods and dimension reduction of the feature space. The predictive model was selected using a 10-fold cross validation procedure and, after selection, it was validated with an independent set to assess its performance when applied to new data and the results were similar to the ones obtained for the training set, supporting the robustness of the proposed approach.ConclusionsThe proposed methodology seemingly improves the prediction performance of standard enthalpy of formation of hydrocarbons using a limited set of molecular descriptors, providing faster and more cost-effective calculation of descriptors by reducing their numbers, and providing a better understanding of the underlying relationship between the molecular structure represented by descriptors and the property of interest.

-The effectiveness of Mediterranean forest ecosystem management calls for the conceptualization and implementation of adequate decision support tools. The proposed decision support system encompasses a management information system, a prescription simulator, a constraint generator and a set of management models designed to solve decision problems. Emphasis is on the architecture of the prescription simulator and its linkage to the three other modules, as well as on methods for reporting and visualizing solutions. Results are discussed for a real world test case -Serra de Grândola, a management area with about 18 600 ha comprising 860 cork oak (Quercus suber L.) land units. Cork oak silviculture adds complexity to the traditional forest management problem. Results show that the devised system is able to address effectively the integration of ecosystem data, silviculture, growth-and-yield and management models. They further suggest that the proposed system architecture may help address the complexity of Mediterranean ecosystem management problems.forest management / Mediterranean ecosystems / prescription simulation / decision support systems / cork oak Résumé -Concevoir des outils de support de décision pour la gestion des écosystèmes forestiers méditerranéens : une étude de cas au Portugal. L'efficacité de gestion de l'écosystème méditerranéen requiert la conception et l'implantation d'outils de support à la décision adaptés. Le système d'aide à la décision proposé comprend un système de gestion de l'information, un simulateur de prescriptions, un généra-teur de contraintes et un ensemble de modèles de gestion conçus pour la résolution de problèmes de décision. L'accent est mis sur la description de l'architecture du simulateur de prescriptions et de ses liens avec les trois autres modules. Sont également décrites les méthodes de présenta-tion et de visualisation de scénarios alternatifs. Les résultats obtenus sur un cas réel, la Serra de Grândola, située au sud du Portugal (qui correspond à la gestion d'une superficie de 18 600 ha dont 860 unités de gestion de chêne liège (Quercus suber L.) ) sont discutés. Le chêne liège est une espèce dont la spécificité engendre une gestion complexe. Les résultats montrent que le système est capable de résoudre avec succès l'intégration des données, des modèles de sylviculture, croissance et développement ainsi que des modèles de gestion. L'analyse des résultats suggère que le système proposé permet de traiter la complexité de gestion de l'écosystème méditerranéen. gestion forestière / écosystème méditerranéen / simulation / système de décison / chêne liège

Despite the structure and objectivity provided by the Gene Ontology (GO), the annotation of proteins is a complex task that is subject to errors and inconsistencies. Electronically inferred annotations in particular are widely considered unreliable. However, given that manual curation of all GO annotations is unfeasible, it is imperative to improve the quality of electronically inferred annotations. In this work, we analyze the full GO molecular function annotation of UniProtKB proteins, and discuss some of the issues that affect their quality, focusing particularly on the lack of annotation consistency. Based on our analysis, we estimate that 64% of the UniProtKB proteins are incompletely annotated, and that inconsistent annotations affect 83% of the protein functions and at least 23% of the proteins. Additionally, we present and evaluate a data mining algorithm, based on the association rule learning methodology, for identifying implicit relationships between molecular function terms. The goal of this algorithm is to assist GO curators in updating GO and correcting and preventing inconsistent annotations. Our algorithm predicted 501 relationships with an estimated precision of 94%, whereas the basic association rule learning methodology predicted 12,352 relationships with a precision below 9%.