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Abstract The druggable proteome refers to proteins that can bind to small molecules with appropriate chemical affinity, inducing a favorable clinical response. Predicting druggable proteins through screening and in silico modeling is imperative for drug design. To contribute to this field, we developed an accurate predictive classifier for druggable cancer-driving proteins using amino acid composition descriptors of protein sequences and 13 machine learning linear and non-linear classifiers. The optimal classifier was achieved with the support vector machine method, utilizing 200 tri-amino acid composition descriptors. The high performance of the model is evident from an area under the receiver operating characteristics (AUROC) of 0.975 ± 0.003 and an accuracy of 0.929 ± 0.006 (threefold cross-validation). The machine learning prediction model was enhanced with multi-omics approaches, including the target-disease evidence score, the shortest pathways to cancer hallmarks, structure-based ligandability assessment, unfavorable prognostic protein analysis, and the oncogenic variome. Additionally, we performed a drug repurposing analysis to identify drugs with the highest affinity capable of targeting the best predicted proteins. As a result, we identified 79 key druggable cancer-driving proteins with the highest ligandability, and 23 of them demonstrated unfavorable prognostic significance across 16 TCGA PanCancer types: CDKN2A, BCL10, ACVR1, CASP8, JAG1, TSC1, NBN, PREX2, PPP2R1A, DNM2, VAV1, ASXL1, TPR, HRAS, BUB1B, ATG7, MARK3, SETD2, CCNE1, MUTYH, CDKN2C, RB1, and SMARCA4. Moreover, we prioritized 11 clinically relevant drugs targeting these proteins. This strategy effectively predicts and prioritizes biomarkers, therapeutic targets, and drugs for in-depth studies in clinical trials. Scripts are available at https://github.com/muntisa/machine-learning-for-druggable-proteins .

This article examines the use of artificial intelligence (AI) in the field of paediatric care within the framework of the 7P medicine model (Predictive, Preventive, Personalized, Precise, Participatory, Peripheral and Polyprofessional). It highlights various applications of AI in the diagnosis, treatment and management of paediatric diseases as well as the role of AI in prevention and in the efficient management of health care resources and the resulting impact on the sustainability of public health systems. Successful cases of the application of AI in the paediatric care setting are presented, placing emphasis on the need to move towards a 7P health care model. Artificial intelligence is revolutionizing society at large and has a great potential for significantly improving paediatric care. Resumen: Se examina el uso de la inteligencia artificial (IA) en el campo de la atención a la salud pediátrica dentro del marco de la ''Medicina de las 7P'' (Predictiva, Preventiva, Personalizada, Precisa, Participativa, Periférica y Poliprofesional). Se destacan diversas aplicaciones de la IA en el diagnóstico, el tratamiento y el control de enfermedades pediátricas, así como su papel en la prevención y en la gestión eficiente de los recursos médicos con su repercusión en la sostenibilidad de los sistemas públicos de salud. Se presentan casos de éxito de la aplicación de la IA en el ámbito pediátrico y se hace un gran énfasis en la necesidad de caminar hacia la Medicina de las 7P. La IA está revolucionando la sociedad en general ofreciendo un gran potencial para mejorar significativamente el cuidado de la salud en pediatría.

Resumen: Se examina el uso de la inteligencia artificial (IA) en el campo de la atención a la salud pediátrica dentro del marco de la «Medicina de las 7P» (Predictiva, Preventiva, Personalizada, Precisa, Participativa, Periférica y Poliprofesional). Se destacan diversas aplicaciones de la IA en el diagnóstico, el tratamiento y el control de enfermedades pediátricas, así como su papel en la prevención y en la gestión eficiente de los recursos médicos con su repercusión en la sostenibilidad de los sistemas públicos de salud. Se presentan casos de éxito de la aplicación de la IA en el ámbito pediátrico y se hace un gran énfasis en la necesidad de caminar hacia la Medicina de las 7P. La IA está revolucionando la sociedad en general ofreciendo un gran potencial para mejorar significativamente el cuidado de la salud en pediatría. Abstract: This article examines the use of artificial intelligence (AI) in the field of paediatric care within the framework of the 7P medicine model (Predictive, Preventive, Personalized, Precise, Participatory, Peripheral and Polyprofessional). It highlights various applications of AI in the diagnosis, treatment and management of paediatric diseases as well as the role of AI in prevention and in the efficient management of health care resources and the resulting impact on the sustainability of public health systems. Successful cases of the application of AI in the paediatric care setting are presented, placing emphasis on the need to move towards a 7P health care model. Artificial intelligence is revolutionizing society at large and has a great potential for significantly improving paediatric care.

Abstract For understanding a chemical compound’s mechanism of action and its side effects, as well as for drug discovery, it is crucial to predict its possible protein targets. This study examines 15 developed target-centric models (TCM) employing different molecular descriptions and machine learning algorithms. They were contrasted with 17 third-party models implemented as web tools (WTCM). In both sets of models, consensus strategies were implemented as potential improvement over individual predictions. The findings indicate that TCM reach f1-score values greater than 0.8. Comparing both approaches, the best TCM achieves values of 0.75, 0.61, 0.25 and 0.38 for true positive/negative rates (TPR, TNR) and false negative/positive rates (FNR, FPR); outperforming the best WTCM. Moreover, the consensus strategy proves to have the most relevant results in the top $$20\%$$ 20 % of target profiles. TCM consensus reach TPR and FNR values of 0.98 and 0; while on WTCM reach values of 0.75 and 0.24. The implemented computational tool with the TCM and their consensus strategy at: https://bioquimio.udla.edu.ec/tidentification01/ . Scientific Contribution: We compare and discuss the performances of 17 public compound-target interaction prediction models and 15 new constructions. We also explore a compound-target interaction prioritization strategy using a consensus approach, and we analyzed the challenging involved in interactions modeling. Graphical Abstract

Single Sign-On (SSO) methods are the primary solution to authenticate users across multiple web systems. These mechanisms streamline the authentication procedure by avoiding duplicate developments of authentication modules for each application. Besides, these mechanisms also provide convenience to the end-user by keeping the user authenticated when switching between different contexts. To ensure this cross-application authentication, SSO relies on an Identity Provider (IdP), which is commonly set up and managed by each institution that needs to enforce SSO internally. However, the solution is not so straightforward when several institutions need to cooperate in a unique ecosystem. This could be tackled by centralizing the authentication mechanisms in one of the involved entities, a solution raising responsibilities that may be difficult for peers to accept. Moreover, this solution is not appropriate for dynamic groups, where peers may join or leave frequently.In this paper, we propose an architecture that uses a trusted third-party service to authenticate multiple entities, ensuring the isolation of the user's attributes between this service and the institutional SSO systems. This architecture was validated in the EHDEN Portal, which includes web tools and services of this European health project, to establish a Federated Authentication schema.

FIDO2 authentication is starting to be applied in numerous web authentication services, aiming to replace passwords and their known vulnerabilities. However, this new authentication method has not been integrated yet with network authentication systems. In this paper, we introduce FIDO2CAP: FIDO2 Captive-portal Authentication Protocol. Our proposal describes a novel protocol for captive-portal network authentication using FIDO2 Authenticators as security keys and passkeys. For validating our proposal, we have developed a prototype of FIDO2CAP authentication in a mock scenario. Using this prototype, we performed a usability experiment with 15 real users. This work makes the first systematic approach for adapting network authentication to the new authentication paradigm relying on FIDO2 authentication.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in the step prior to preclinical studies. This stage manages to drastically reduce costs and research times in the discovery of new drugs. This review article focuses on how these new methodologies are being used in recent years of research. Analyzing the state of the art in this field will give us an idea of where cheminformatics will be developed in the short term, the limitations it presents and the positive results it has achieved. This review will focus mainly on the methods used to model the molecular data, as well as the biological problems addressed and the Machine Learning algorithms used for drug discovery in recent years.

Abstract Background The main challenge in cancer research is the identification of different omic variables that present a prognostic value and personalised diagnosis for each tumour. The fact that the diagnosis is personalised opens the doors to the design and discovery of new specific treatments for each patient. In this context, this work offers new ways to reuse existing databases and work to create added value in research. Three published signatures with significante prognostic value in Colon Adenocarcinoma (COAD) were indentified. These signatures were combined in a new meta-signature and validated with main Machine Learning (ML) and conventional statistical techniques. In addition, a drug repurposing experiment was carried out through Molecular Docking (MD) methodology in order to identify new potential treatments in COAD. Results The prognostic potential of the signature was validated by means of ML algorithms and differential gene expression analysis. The results obtained supported the possibility that this meta-signature could harbor genes of interest for the prognosis and treatment of COAD. We studied drug repurposing following a molecular docking (MD) analysis, where the different protein data bank (PDB) structures of the genes of the meta-signature (in total 155) were confronted with 81 anti-cancer drugs approved by the FDA. We observed four interactions of interest: GLTP - Nilotinib, PTPRN - Venetoclax, VEGFA - Venetoclax and FABP6 - Abemaciclib. The FABP6 gene and its role within different metabolic pathways were studied in tumour and normal tissue and we observed the capability of the FABP6 gene to be a therapeutic target. Our in silico results showed a significant specificity of the union of the protein products of the FABP6 gene as well as the known action of Abemaciclib as an inhibitor of the CDK4/6 protein and therefore, of the cell cycle. Conclusions The results of our ML and differential expression experiments have first shown the FABP6 gene as a possible new cancer biomarker due to its specificity in colonic tumour tissue and no expression in healthy adjacent tissue. Next, the MD analysis showed that the drug Abemaciclib characteristic affinity for the different protein structures of the FABP6 gene. Therefore, in silico experiments have shown a new opportunity that should be validated experimentally, thus helping to reduce the cost and speed of drug screening. For these reasons, we propose the validation of the drug Abemaciclib for the treatment of colon cancer.

Background:: Many scientific studies have sought to obtain a better understanding of specific medical conditions. Concerning Alzheimer’s Disease, there is a lack of reliable diagnostics and this can be related to the availability of only small-scale ongoing biomarker studies and longitudinal cohorts including these subjects. Aiming to generate more substantial clinical evidence, researchers have started to perform multiple cohort analyses. While this is currently possible by harmonising these cohorts into a common data model, the migration pipelines are usually implemented using programming languages. Therefore, cohort owners may have difficulties contributing during the validation stage of these pipelines. Results:: To reduce the dependency on technical teams’ support when validating the data transformations, it is proposed the use of an ETL tool with visual features. BIcenter is a collaborative web platform designed to implement ETL tasks through the browser. These pipelines are constructed using drag-and-drop features and intuitive forms to customise the ETL steps. This tool is an open-source project and is accessible at https://bioinformatics-ua.github.io/BIcenter-AD/. Conclusions:: Our methodology produces interoperable cohorts for multicentric disease-specific studies. Therefore, the tool was validated using Alzheimer’s Disease cohorts from several countries, combining at the end 6,669 subjects and 172 medical attributes. The harmonised cohorts now enable multi-cohort querying and analysis, helping in the execution of new studies.

In recent years, machine learning (ML) researchers have changed their focus towards biological problems that are difficult to analyse with standard approaches. Large initiatives such as The Cancer Genome Atlas (TCGA) have allowed the use of omic data for the training of these algorithms. In order to study the state of the art, this review is provided to cover the main works that have used ML with TCGA data. Firstly, the principal discoveries made by the TCGA consortium are presented. Once these bases have been established, we begin with the main objective of this study, the identification and discussion of those works that have used the TCGA data for the training of different ML approaches. After a review of more than 100 different papers, it has been possible to make a classification according to following three pillars: the type of tumour, the type of algorithm and the predicted biological problem. One of the conclusions drawn in this work shows a high density of studies based on two major algorithms: Random Forest and Support Vector Machines. We also observe the rise in the use of deep artificial neural networks. It is worth emphasizing, the increase of integrative models of multi-omic data analysis. The different biological conditions are a consequence of molecular homeostasis, driven by both protein coding regions, regulatory elements and the surrounding environment. It is notable that a large number of works make use of genetic expression data, which has been found to be the preferred method by researchers when training the different models. The biological problems addressed have been classified into five types: prognosis prediction, tumour subtypes, microsatellite instability (MSI), immunological aspects and certain pathways of interest. A clear trend was detected in the prediction of these conditions according to the type of tumour. That is the reason for which a greater number of works have focused on the BRCA cohort, while specific works for survival, for example, were centred on the GBM cohort, due to its large number of events. Throughout this review, it will be possible to go in depth into the works and the methodologies used to study TCGA cancer data. Finally, it is intended that this work will serve as a basis for future research in this field of study.

Food consumption patterns have undergone changes that in recent years have resulted in serious health problems. Studies based on the evaluation of the nutritional status have determined that the adoption of a food pattern-based primarily on a Mediterranean diet (MD) has a preventive role, as well as the ability to mitigate the negative effects of certain pathologies. A group of more than 500 adults aged over 40 years from our cohort in Northwestern Spain was surveyed. Under our experimental design, 10 experiments were run with four different machine-learning algorithms and the predictive factors most relevant to the adherence of a MD were identified. A feature selection approach was explored and under a null hypothesis test, it was concluded that only 16 measures were of relevance, suggesting the strength of this observational study. Our findings indicate that the following factors have the highest predictive value in terms of the degree of adherence to the MD: basal metabolic rate, mini nutritional assessment questionnaire total score, weight, height, bone density, waist-hip ratio, smoking habits, age, EDI-OD, circumference of the arm, activity metabolism, subscapular skinfold, subscapular circumference in cm, circumference of the waist, circumference of the calf and brachial area.

Abstract Biological Ecosystem Networks (BENs) are webs of biological species (nodes) establishing trophic relationships (links). Experimental confirmation of all possible links is difficult and generates a huge volume of information. Consequently, computational prediction becomes an important goal. Artificial Neural Networks (ANNs) are Machine Learning (ML) algorithms that may be used to predict BENs, using as input Shannon entropy information measures (Shk) of known ecosystems to train them. However, it is difficult to select a priori which ANN topology will have a higher accuracy. Interestingly, Auto Machine Learning (AutoML) methods focus on the automatic selection of the more efficient ML algorithms for specific problems. In this work, a preliminary study of a new approach to AutoML selection of ANNs is proposed for the prediction of BENs. We call it the Net-Net AutoML approach, because it uses for the first time Shk values of both networks involving BENs (networks to be predicted) and ANN topologies (networks to be tested). Twelve types of classifiers have been tested for the Net-Net model including linear, Bayesian, trees-based methods, multilayer perceptrons and deep neuronal networks. The best Net-Net AutoML model for 338,050 outputs of 10 ANN topologies for links of 69 BENs was obtained with a deep fully connected neuronal network, characterized by a test accuracy of 0.866 and a test AUROC of 0.935. This work paves the way for the application of Net-Net AutoML to other systems or ML algorithms.

Among the bovine diseases, mastitis causes high economic losses in the dairy production system. Nowadays, detection under field conditions is mainly performed by the California Mastitis Test, which is considered the de facto standard. However, this method presents with problems of slowness and the expensiveness of the chemical-reactive process, which is deeply dependent on an expert’s trained eye and, consequently, is highly imprecise. The aim of this work is to propose a new method for bovine mastitis detection under field conditions. The proposed method uses a low-cost, smartphone-connected NIR spectrometer which solves the aforementioned problems of slowness, expert dependency and disposability of the chemical methods. This method uses spectra in combination with two k-Nearest Neighbors models. The first model is used to detect the presence of mastitis while the second model classifies the positive cases into weak and strong. The resulting method was validated by using a leave-one-out technique where the ground truth was obtained by the California Mastitis Test. The detection model achieved an accuracy of 92.4%, while the one classifying the severity showed an accuracy of 95%.

Abstract Background Ontologies and controlled terminologies have become increasingly important in biomedical research. Researchers use ontologies to annotate their data with ontology terms, enabling better data integration and interoperability across disparate datasets. However, the number, variety and complexity of current biomedical ontologies make it cumbersome for researchers to determine which ones to reuse for their specific needs. To overcome this problem, in 2010 the National Center for Biomedical Ontology (NCBO) released the Ontology Recommender, which is a service that receives a biomedical text corpus or a list of keywords and suggests ontologies appropriate for referencing the indicated terms. Methods We developed a new version of the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a novel recommendation approach that evaluates the relevance of an ontology to biomedical text data according to four different criteria: (1) the extent to which the ontology covers the input data; (2) the acceptance of the ontology in the biomedical community; (3) the level of detail of the ontology classes that cover the input data; and (4) the specialization of the ontology to the domain of the input data. Results Our evaluation shows that the enhanced recommender provides higher quality suggestions than the original approach, providing better coverage of the input data, more detailed information about their concepts, increased specialization for the domain of the input data, and greater acceptance and use in the community. In addition, it provides users with more explanatory information, along with suggestions of not only individual ontologies but also groups of ontologies to use together. It also can be customized to fit the needs of different ontology recommendation scenarios. Conclusions Ontology Recommender 2.0 suggests relevant ontologies for annotating biomedical text data. It combines the strengths of its predecessor with a range of adjustments and new features that improve its reliability and usefulness. Ontology Recommender 2.0 recommends over 500 biomedical ontologies from the NCBO BioPortal platform, where it is openly available (both via the user interface at http://bioportal.bioontology.org/recommender , and via a Web service API).

Objetivos: obtener un perfil sobre capacidad funcional y participación de personas con Enfermedades Neuromusculares (ENM), y determinar los recursos de apoyo necesarios para mejorar o mantener su grado de independencia. Metodología: estudio transversal con 24 personas con ENM. En la evaluación se emplearon la Medida de Independencia Funcional (FIM), un checklist de accesibilidad de la vivienda y un cuestionario específico. Resultados: muestra formada por catorce mujeres (58,3 %) y 10 hombres (41,7 %). Se obtuvo una media de 61,7 (DE=17,2) para la parte motora de FIM sobre 91, indicando un grado moderado de dependencia. El producto de apoyo (PA) más frecuentemente empleado fue la silla de ruedas (70,8 %). La mayoría de las viviendas (87,5 %) presentaban barreras arquitectónicas. Conclusiones: la evaluación concisa sobre necesidades de independencia de personas con ENM es fundamental para prescribir los recursos más adecuados para satisfacerlas. Este procedimiento se debe implementar en programas asistenciales, incluyendo la atención al cuidador.

Air pollution is the fourth-largest overall risk factor for human health worldwide. Ambient air pollution (outdoors) and household air pollution (indoors) cause about 6.5 million premature deaths. The World Health Organization has established that between 3% and 14% of lung cancer cases are due to radon gas, making it the most important cause of lung cancer after smoking. This work presents a fully automated, low-cost indoor air quality control system that can monitor temperature, pressure, humidity, total volatile organic compounds (TOVC), and radon concentration. Using the radon concentration as an air quality measure, we created a prediction algorithm. The system uses those predictions to control a ventilation system automatically. We tested the algorithm for different prediction windows and compared the results with those without the ventilation system in a radon research room. In this room, the radon concentration is high 100% of the time, reaching a level eleven times higher than the recommended limit. The results show that the system can achieve an 86% reduction of the radon concentration, maintaining it low 90% of the time while having the ventilation system on during only 34% of the time. This work demonstrates that we can control air quality using low-cost resources, keeping a household or workplace safe but comfortable.

The advances achieved in recent decades regarding cardiac surgery have led to a new risk that goes beyond surgeons’ dexterity; postoperative hours are crucial for cardiac surgery patients and are usually spent in intensive care units (ICUs), where the patients need to be continuously monitored to adjust their treatment. Clinical decision support systems (CDSSs) have been developed to take this real-time information and provide clinical suggestions to physicians in order to reduce medical errors and to improve patient recovery. In this review, an initial total of 499 papers were considered after identification using PubMed, Web of Science, and CINAHL. Twenty-two studies were included after filtering, which included the deletion of duplications and the exclusion of titles or abstracts that were not of real interest. A review of these papers concluded the applicability and advances that CDSSs offer for both doctors and patients. Better prognosis and recovery rates are achieved by using this technology, which has also received high acceptance among most physicians. However, despite the evidence that well-designed CDSSs are effective, they still need to be refined to offer the best assistance possible, which may still take time, despite the promising models that have already been applied in real ICUs.

The study of the intestinal microbiota is one of the biggest challenges in the current clinical environment. In this context, probiotics have been a focus of interest to achieve the stability of the intestinal microbiota, due to probiotics’ key role in its regulation. The development of an automated system that allows practitioners to easily search for the optimal probiotic is the main objective of this study. Although it is true that there have been previous attempts of applications with this purpose, only authorized probiotics available in the countries of origin, Canada and the USA, were included. This event was a limitation when looking for those endorsed in other countries such as Spain. Thus, a system has been developed from free and multiplatform technologies that allow its use without any cost, finding, in a simple way, those probiotics that would be ideal for each pathology, either from a browser or from a cell phone.

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.

The study of the intestinal microbiota is one of the greatest challenges in today’s clinical environment. Thus, probiotics have been established as a focus for its stability, as they play a key role in its regulation. The development of an automated technique that allows the practitioners the smooth search for the optimal probiotic is postulated as the main objective of this study. Despite the existence of previous attempts at applications for this purpose, they have only been carried out for the countries of origin, preventing them from being used in others such as Spain. Therefore, a system has been developed with open, multi-platform, and free technologies, which manages to locate the optimal probiotic for each pathology.

This paper proposes a new model for music prediction based on Variational Autoencoders (VAEs). In this work, VAEs are used in a novel way to address two different issues: music representation into the latent space, and using this representation to make predictions of the future note events of the musical piece. This approach was trained with different songs of Handel. As a result, the system can represent the music in the latent space, and make accurate predictions. Therefore, the system can be used to compose new music either from an existing piece or from a random starting point. An additional feature of this system is that a small dataset was used for training. However, results show that the system is able to return accurate representations and predictions on unseen data.

Brain Connectome Networks (BCNs) are defined by brain cortex regions (nodes) interacting with others by electrophysiological co-activation (edges). The experimental prediction of new interactions in BCNs represents a difficult task due to the large number of edges and the complex connectivity patterns. Fortunately, we can use another special type of networks to achieve this goal—Artificial Neural Networks (ANNs). Thus, ANNs could use node descriptors such as Shannon Entropies (Sh) to predict node connectivity for large datasets including complex systems such as BCN. However, the training of a high number of ANNs for BCNs is a time-consuming task. In this work, we propose the use of a method to automatically determine which ANN topology is more efficient for the BCN prediction. Since a network (ANN) is used to predict the connectivity in another network (BCN), this method was entitled Net-Net AutoML. The algorithm uses Sh descriptors for pairs of nodes in BCNs and for ANN predictors of BCNs. Therefore, it is able to predict the efficiency of new ANN topologies to predict BCNs. The current study used a set of 500,470 examples from 10 different ANNs to predict node connectivity in BCNs and 20 features. After testing five Machine Learning classifiers, the best classification model to predict the ability of an ANN to evaluate node interactions in BCNs was provided by Random Forest (mean test AUROC of 0.9991 ± 0.0001, 10-fold cross-validation). Net-Net AutoML algorithms based on entropy descriptors may become a useful tool in the design of automatic expert systems to select ANN topologies for complex biological systems. The scripts and dataset for this project are available in an open GitHub repository.

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein−protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

Increasing the energy efficiency of buildings is a strategic objective in the European Union, and it is the main reason why numerous studies have been carried out to evaluate and reduce energy consumption in the residential sector. The process of evaluation and qualification of the energy efficiency in existing buildings should contain an analysis of the thermal behavior of the building envelope. To determine this thermal behavior and its representative parameters, we usually have to use destructive auscultation techniques in order to determine the composition of the different layers of the envelope. In this work, we present a nondestructive, fast, and cheap technique based on artificial neural network (ANN) models that predict the energy performance of a house, given some of its characteristics. The models were created using a dataset of buildings of different typologies and uses, located in the northern area of Spain. In this dataset, the models are able to predict the U-opaque value of a building with a correlation coefficient of 0.967 with the real U-opaque measured value for the same building.

The electrokinetic properties of the rumen microbiota are involved in cell surface adhesion and microbial metabolism. An in vitro study was carried out in batch culture to determine the effects of three levels of special surface area (SSA) of biomaterials and four levels of surface tension (ST) of culture medium on electrokinetic properties (Zeta potential, ξ; electrokinetic mobility, μe), fermentation parameters (volatile fatty acids, VFAs), and ST over fermentation processes (ST-a, γ). The obtained results were combined with previously published data (digestibility, D; pH; concentration of ammonia nitrogen, c(NH3-N)) to establish a predictive artificial neural network (ANN) model. Concepts of dual-time series analysis, perturbation theory (PT), and Box-Jenkins Operators were applied for the first time to develop an ANN model to predict the variations of the electrokinetic properties of microbiota. The best dual-time series Radial Basis Functions (RBR) model for ξ of rumen microbiota predicted ξ for >30,000 cases with a correlation coefficient >0.8. This model provided insight into the correlations between electrokinetic property (zeta potential) of rumen microbiota and the perturbations of physical factors (specific surface area and surface tension) of media, digestibility of substrate, and their metabolites (NH3-N, VFAs) in relation to environmental factors.

The design of experiments and the validation of the results achieved with them are vital in any research study. This paper focuses on the use of different Machine Learning approaches for regression tasks in the field of Computational Intelligence and especially on a correct comparison between the different results provided for different methods, as those techniques are complex systems that require further study to be fully understood. A methodology commonly accepted in Computational intelligence is implemented in an R package called RRegrs. This package includes ten simple and complex regression models to carry out predictive modeling using Machine Learning and well-known regression algorithms. The framework for experimental design presented herein is evaluated and validated against RRegrs. Our results are different for three out of five state-of-the-art simple datasets and it can be stated that the selection of the best model according to our proposal is statistically significant and relevant. It is of relevance to use a statistical approach to indicate whether the differences are statistically significant using this kind of algorithms. Furthermore, our results with three real complex datasets report different best models than with the previously published methodology. Our final goal is to provide a complete methodology for the use of different steps in order to compare the results obtained in Computational Intelligence problems, as well as from other fields, such as for bioinformatics, cheminformatics, etc., given that our proposal is open and modifiable.

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.

The artificial neural networks used in a multitude of fields are achieving good results. However, these systems are inspired in the vision of classical neuroscience where neurons are the only elements that process information in the brain. Advances in neuroscience have shown that there is a type of glial cell called astrocytes that collaborate with neurons to process information. In this work, a connectionist system formed by neurons and artificial astrocytes is presented. The astrocytes can have different configurations to achieve a biologically more realistic behaviour. This work indicates that the use of different artificial astrocytes behaviours is beneficial.

Single nucleotide polymorphisms (SNPs) can be used as inputs in disease computational studies such as pattern searching and classification models. Schizophrenia is an example of a complex disease with an important social impact. The multiple causes of this disease create the need of new genetic or proteomic patterns that can diagnose patients using biological information. This work presents a computational study of disease machine learning classification models using only single nucleotide polymorphisms at the HTR2A and DRD3 genes from Galician (Northwest Spain) schizophrenic patients. These classification models establish for the first time, to the best knowledge of the authors, a relationship between the sequence of the nucleic acid molecule and schizophrenia (Quantitative Genotype – Disease Relationships) that can automatically recognize schizophrenia DNA sequences and correctly classify between 78.3–93.8% of schizophrenia subjects when using datasets which include simulated negative subjects and a linear artificial neural network.

El framework J2EE ha sido el gran dominador, durante mucho tiempo, en el desarrollo de aplicaciones empresariales. Esto hecho originó la aparición de un rico ecosistema de herramientas, manuales, tutoriales, etc., que explican las diferentes alternativas o peculiaridades a la hora de su implementación. La irrupción de .NET Framework, en el ámbito empresarial, ha producido una fuerte demanda de implementación de aplicaciones bajo dicha arquitectura. Sin embargo, la cantidad o calidad de la documentación disponible dista considerablemente con respecto a la existente, su principal alternativa (J2EE). Esta laguna de documentación, es especialmente visible y preocupante cuando se establece como objetivo dar a conocer los conceptos del framework, desde un punto de vista docente, a los futuros egresados del Grado en Ingeniería en Informática. Este trabajo describe el enfoque docente seguido, para alcanzar el citado objetivo de familiarizar a los alumnos con este framework alternativo y las prácticas habituales de modelo dentro de éste. Para ello, se basa principalmente de un conjunto de sencillos tutoriales con los que mostrar los fundamentos de la tecnología y dos aplicaciones completas (miniportal y minibank) en las que se muestra cómo aplicar patrones de diseño, a la hora de abordar una aplicación empresarial.

This study presents the impact of carbon nanotubes (CNTs) on mitochondrial oxygen mass flux (Jm) under three experimental conditions. New experimental results and a new methodology are reported for the first time and they are based on CNT Raman spectra star graph transform (spectral moments) and perturbation theory. The experimental measures of Jm showed that no tested CNT family can inhibit the oxygen consumption profiles of mitochondria. The best model for the prediction of Jm for other CNTs was provided by random forest using eight features, obtaining test R-squared (R2) of 0.863 and test root-mean-square error (RMSE) of 0.0461. The results demonstrate the capability of encoding CNT information into spectral moments of the Raman star graphs (SG) transform with a potential applicability as predictive tools in nanotechnology and material risk assessments.

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Over the past decade, Deep Artificial Neural Networks (DNNs) have become the state-of-the-art algorithms in Machine Learning (ML), speech recognition, computer vision, natural language processing and many other tasks. This was made possible by the advancement in Big Data, Deep Learning (DL) and drastically increased chip processing abilities, especially general-purpose graphical processing units (GPGPUs). All this has created a growing interest in making the most of the potential offered by DNNs in almost every field. An overview of the main architectures of DNNs, and their usefulness in Pharmacology and Bioinformatics are presented in this work. The featured applications are: drug design, virtual screening (VS), Quantitative Structure–Activity Relationship (QSAR) research, protein structure prediction and genomics (and other omics) data mining. The future need of neuromorphic hardware for DNNs is also discussed, and the two most advanced chips are reviewed: IBM TrueNorth and SpiNNaker. In addition, this review points out the importance of considering not only neurons, as DNNs and neuromorphic chips should also include glial cells, given the proven importance of astrocytes, a type of glial cell which contributes to information processing in the brain. The Deep Artificial Neuron–Astrocyte Networks (DANAN) could overcome the difficulties in architecture design, learning process and scalability of the current ML methods.

Compelling evidence indicates the existence of bidirectional communication between astrocytes and neurons. Astrocytes, a type of glial cells classically considered to be passive supportive cells, have been recently demonstrated to be actively involved in the processing and regulation of synaptic information, suggesting that brain function arises from the activity of neuron-glia networks. However, the actual impact of astrocytes in neural network function is largely unknown and its application in artificial intelligence remains untested. We have investigated the consequences of including artificial astrocytes, which present the biologically defined properties involved in astrocyte-neuron communication, on artificial neural network performance. Using connectionist systems and evolutionary algorithms, we have compared the performance of artificial neural networks (NN) and artificial neuron-glia networks (NGN) to solve classification problems. We show that the degree of success of NGN is superior to NN. Analysis of performances of NN with different number of neurons or different architectures indicate that the effects of NGN cannot be accounted for an increased number of network elements, but rather they are specifically due to astrocytes. Furthermore, the relative efficacy of NGN vs. NN increases as the complexity of the network increases. These results indicate that artificial astrocytes improve neural network performance, and established the concept of Artificial Neuron-Glia Networks, which represents a novel concept in Artificial Intelligence with implications in computational science as well as in the understanding of brain function.