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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.

Background:: Data catalogues are used in multiple domains to provide an overview of databases’ characteristics without releasing the actual data. Despite the existence of several web-based catalogues, they do not always meet the needs of certain domains. In the healthcare field, they need to give multiple and iterative views to the data, from high-level metadata up to low-level samples or patient data. This approach is critical to help researchers find relevant datasets for their studies. Methods:: In this paper, we present MONTRA2, a web platform for profiling distributed databases. The users’ requirements were designed in the context of the EHDEN European project, in close collaboration with medical researchers, data owners, and pharmaceutical companies, leading to a rich set of functionalities to support databases and cohorts discovery. The platform was developed with a modular architecture which simplifies the integration of internal and external services. Results:: MONTRA2 is successfully being used in several European projects and research initiatives, focused on the dissemination and sharing of biomedical databases. In this paper, we present three health data catalogues that were built upon the core of this framework. MONTRA2 is publicly available under the MIT license at https://github.com/bioinformatics-ua/montra2. Conclusions:: The execution of federated studies on a large scale and involving multiple centres is only possible if adequate tools for data management and discovery are available. By providing tools for study management, database characterisation and publishing, among others, MONTRA2 simplifies the process of setting up a workspace for a community to expose the characteristics of datasets and provide multiple strategies for data analysis.

Abstract Over the years, a growing number of semantic data repositories have been made available on the web. However, this has created new challenges in exploiting these resources efficiently. Querying services require knowledge beyond the typical user’s expertise, which is a critical issue in adopting semantic information solutions. Several proposals to overcome this difficulty have suggested using question answering (QA) systems to provide user‐friendly interfaces and allow natural language use. Because question answering over knowledge bases (KBQAs) is a very active research topic, a comprehensive view of the field is essential. The purpose of this study was to conduct a systematic review of methods and systems for KBQAs to identify their main advantages and limitations. The inclusion criteria rationale was English full‐text articles published since 2015 on methods and systems for KBQAs. Sixty‐six articles were reviewed to describe their underlying reference architectures.

Heart failure with preserved ejection fraction (HFpEF) represents a global health challenge, with limited therapies proven to enhance patient outcomes. This makes the elucidation of disease mechanisms and the identification of novel potential therapeutic targets a priority. Here, we performed RNA sequencing on ventricular myocardial biopsies from patients with HFpEF, prospecting to discover distinctive transcriptomic signatures. A total of 306 differentially expressed mRNAs (DEG) and 152 differentially expressed microRNAs (DEM) were identified and enriched in several biological processes involved in HF. Moreover, by integrating mRNA and microRNA expression data, we identified five potentially novel miRNA–mRNA relationships in HFpEF: the upregulated hsa-miR-25-3p, hsa-miR-26a-5p, and has-miR4429, targeting HAPLN1; and NPPB mRNA, targeted by hsa-miR-26a-5p and miR-140-3p. Exploring the predicted miRNA–mRNA interactions experimentally, we demonstrated that overexpression of the distinct miRNAs leads to the downregulation of their target genes. Interestingly, we also observed that microRNA signatures display a higher discriminative power to distinguish HFpEF sub-groups over mRNA signatures. Our results offer new mechanistic clues, which can potentially translate into new HFpEF therapies.

Abstract Background Heart disease is the leading cause of death worldwide. Knowing a gene expression signature in heart disease can lead to the development of more efficient diagnosis and treatments that may prevent premature deaths. A large amount of microarray data is available in public repositories and can be used to identify differentially expressed genes. However, most of the microarray datasets are composed of a reduced number of samples and to obtain more reliable results, several datasets have to be merged, which is a challenging task. The identification of differentially expressed genes is commonly done using statistical methods. Nonetheless, these methods are based on the definition of an arbitrary threshold to select the differentially expressed genes and there is no consensus on the values that should be used. Results Nine publicly available microarray datasets from studies of different heart diseases were merged to form a dataset composed of 689 samples and 8354 features. Subsequently, the adjusted p-value and fold change were determined and by combining a set of adjusted p-values cutoffs with a list of different fold change thresholds, 12 sets of differentially expressed genes were obtained. To select the set of differentially expressed genes that has the best accuracy in classifying samples from patients with heart diseases and samples from patients with no heart condition, the random forest algorithm was used. A set of 62 differentially expressed genes having a classification accuracy of approximately 95% was identified. Conclusions We identified a gene expression signature common to different cardiac diseases and supported our findings by showing their involvement in the pathophysiology of the heart. The approach used in this study is suitable for the identification of gene expression signatures, and can be extended to different diseases.

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.

Abstract Background Many healthcare databases have been routinely collected over the past decades, to support clinical practice and administrative services. However, their secondary use for research is often hindered by restricted governance rules. Furthermore, health research studies typically involve many participants with complementary roles and responsibilities which require proper process management. Results From a wide set of requirements collected from European clinical studies, we developed TASKA, a task/workflow management system that helps to cope with the socio-technical issues arising when dealing with multidisciplinary and multi-setting clinical studies. The system is based on a two-layered architecture: 1) the backend engine, which follows a micro-kernel pattern, for extensibility, and RESTful web services, for decoupling from the web clients; 2) and the client, entirely developed in ReactJS, allowing the construction and management of studies through a graphical interface. TASKA is a GNU GPL open source project, accessible at https://github.com/bioinformatics-ua/taska. A demo version is also available at https://bioinformatics.ua.pt/taska. Conclusions The system is currently used to support feasibility studies across several institutions and countries, in the context of the European Medical Information Framework (EMIF) project. The tool was shown to simplify the set-up of health studies, the management of participants and their roles, as well as the overall governance process.

Many clinical trials and scientific studies have been conducted aiming for better understanding of specific medical conditions. However, these studies are often based on a small number of participants due to the difficulty in finding people with similar medical characteristics and available to participate in the studies. This is particularly critical in rare diseases, where the reduced number of subjects hinders reliable findings. To generate more substantial clinical evidence by increasing the power of the analyses, researchers have started to perform data harmonisation and multiple cohort analyses. However, the analysis of heterogeneous data sources implies dealing with different data structures, terminologies, concepts, languages and, most importantly, the knowledge behind the data.In this paper, we present a methodology to harmonise different cohorts into a standard data schema, helping the research community to generate evidence from a wider variety of data sources. Our methodology was inspired by the OHDSI Common Data Model, which aims to harmonise EHR datasets for observational studies, leveraging on knowledge and open source tools to perform multicentric disease-specific studies. This proposal was validated using Alzheimer’s Disease cohorts from several countries, combining at the end 6,669 subjects and 172 clinical concepts. The harmonised datasets now enable multi-cohort querying and analysis, helping in the execution of new research. The methodology was implemented in Python language and is available, under the MIT licence, at https://bioinformatics-ua.github.io/CMToolkit/.

The fast increasing amount of articles published in the biomedical field is creating difficulties in the way this wealth of information can be efficiently exploited by researchers. As a way of overcoming these limitations and potentiating a more efficient use of the literature, we propose an approach for structuring the results of a literature search based on the latent semantic information extracted from a corpus. Moreover, we show how the results of the Latent Semantic Analysis method can be adapted so as to evidence differences between results of different searches. We also propose different visualization techniques that can be applied to explore these results. Used in combination, these techniques could empower users with tools for literature guided knowledge exploration and discovery.

The fast increasing amount of articles published in the biomedical field is creating difficulties in the way this wealth of information can be efficiently exploited by researchers. As a way of overcoming these limitations and potentiating a more efficient use of the literature, we propose an approach for structuring the results of a literature search based on the latent semantic information extracted from a corpus. Moreover, we show how the results of the Latent Semantic Analysis method can be adapted so as to evidence differences between results of different searches. We also propose different visualization techniques that can be applied to explore these results. Used in combination, these techniques could empower users with tools for literature guided knowledge exploration and discovery.

De novo experimental drug discovery is an expensive and time-consuming task. It requires the identification of drug-target interactions (DTIs) towards targets of biological interest, either to inhibit or enhance a specific molecular function. Dedicated computational models for protein simulation and DTI prediction are crucial for speed and to reduce the costs associated with DTI identification. In this paper we present a computational pipeline that enables the discovery of putative leads for drug repositioning that can be applied to any microbial proteome, as long as the interactome of interest is at least partially known. Network metrics calculated for the interactome of the bacterial organism of interest were used to identify putative drug-targets. Then, a random forest classification model for DTI prediction was constructed using known DTI data from publicly available databases, resulting in an area under the ROC curve of 0.91 for classification of out-of-sampling data. A drug-target network was created by combining 3,081 unique ligands and the expected ten best drug targets. This network was used to predict new DTIs and to calculate the probability of the positive class, allowing the scoring of the predicted instances. Molecular docking experiments were performed on the best scoring DTI pairs and the results were compared with those of the same ligands with their original targets. The results obtained suggest that the proposed pipeline can be used in the identification of new leads for drug repositioning. The proposed classification model is available at http://bioinformatics.ua.pt/software/dtipred/.

With the proliferation of social networks and blogs, the Internet is increasingly being used to disseminate personal health information rather than just as a source of information. In this paper we exploit the wealth of user-generated data, available through the micro-blogging service Twitter, to estimate and track the incidence of health conditions in society. The method is based on two stages: we start by extracting possibly relevant tweets using a set of specially crafted regular expressions, and then classify these initial messages using machine learning methods. Furthermore, we selected relevant features to improve the results and the execution times. To test the method, we considered four health states or conditions, namely flu, depression, pregnancy and eating disorders, and two locations, Portugal and Spain. We present the results obtained and demonstrate that the detection results and the performance of the method are improved after feature selection. The results are promising, with areas under the receiver operating characteristic curve between 0.7 and 0.9, and f-measure values around 0.8 and 0.9. This fact indicates that such approach provides a feasible solution for measuring and tracking the evolution of health states within the society.

Pharmacovigilance plays a key role in the healthcare domain through the assessment, monitoring and discovery of interactions amongst drugs and their effects in the human organism. However, technological advances in this field have been slowing down over the last decade due to miscellaneous legal, ethical and methodological constraints. Pharmaceutical companies started to realize that collaborative and integrative approaches boost current drug research and development processes. Hence, new strategies are required to connect researchers, datasets, biomedical knowledge and analysis algorithms, allowing them to fully exploit the true value behind state-of-the-art pharmacovigilance efforts. This manuscript introduces a new platform directed towards pharmacovigilance knowledge providers. This system, based on a service-oriented architecture, adopts a plugin-based approach to solve fundamental pharmacovigilance software challenges. With the wealth of collected clinical and pharmaceutical data, it is now possible to connect knowledge providers' analysis and exploration algorithms with real data. As a result, new strategies allow a faster identification of high-risk interactions between marketed drugs and adverse events, and enable the automated uncovering of scientific evidence behind them. With this architecture, the pharmacovigilance field has a new platform to coordinate large-scale drug evaluation efforts in a unique ecosystem, publicly available at http://bioinformatics.ua.pt/euadr/.