Integrating heterogeneous data to facilitate COVID-19 drug repurposing.

In the COVID-19 pandemic, drug repositioning has presented itself as an alternative to the time-consuming process of generating new drugs. This review describes a drug repurposing process that is based on a new data-driven approach: we put forward five information paths that associate COVID-19-related genes and COVID-19 symptoms with drugs that directly target these gene products, that target the symptoms or that treat diseases that are symptomatically or genetically similar to COVID-19. The intersection of the five information paths results in a list of 13 drugs that we suggest as potential candidates against COVID-19. In addition, we have found information in published studies and in clinical trials that support the therapeutic potential of the drugs in our final list.

Classifying diseases by using biological features to identify potential nosological models.

Established nosological models have provided physicians an adequate enough classification of diseases so far. Such systems are important to correctly identify diseases and treat them successfully. However, these taxonomies tend to be based on phenotypical observations, lacking a molecular or biological foundation. Therefore, there is an urgent need to modernize them in order to include the heterogeneous information that is produced in the present, as could be genomic, proteomic, transcriptomic and metabolic data, leading this way to more comprehensive and robust structures. For that purpose, we have developed an extensive methodology to analyse the possibilities when it comes to generate new nosological models from biological features. Different datasets of diseases have been considered, and distinct features related to diseases, namely genes, proteins, metabolic pathways and genetical variants, have been represented as binary and numerical vectors. From those vectors, diseases distances have been computed on the basis of several metrics. Clustering algorithms have been implemented to group diseases, generating different models, each of them corresponding to the distinct combinations of the previous parameters. They have been evaluated by means of intrinsic metrics, proving that some of them are highly suitable to cover new nosologies. One of the clustering configurations has been deeply analysed, demonstrating its quality and validity in the research context, and further biological interpretations have been made. Such model was particularly generated by OPTICS clustering algorithm, by studying the distance between diseases based on gene sharedness and following cosine index metric. 729 clusters were formed in this model, which obtained a Silhouette coefficient of 0.43.

A data-driven methodology towards evaluating the potential of drug repurposing hypotheses.

Drug repurposing has become a widely used strategy to accelerate the process of finding treatments. While classical de novo drug development involves high costs, risks, and time-consuming paths, drug repurposing allows to reuse already-existing and approved drugs for new indications. Numerous research has been carried out in this field, both in vitro and in silico. Computational drug repurposing methods make use of modern heterogeneous biomedical data to identify and prioritize new indications for old drugs. In the current paper, we present a new complete methodology to evaluate new potentially repurposable drugs based on disease-gene and disease-phenotype associations, identifying significant differences between repurposing and non-repurposing data. We have collected a set of known successful drug repurposing case studies from the literature and we have analysed their dissimilarities with other biomedical data not necessarily participating in repurposing processes. The information used has been obtained from the DISNET platform. We have performed three analyses (at the genetical, phenotypical, and categorization levels), to conclude that there is a statistically significant difference between actual repurposing-related information and non-repurposing data. The insights obtained could be relevant when suggesting new potential drug repurposing hypotheses.

Collective intelligence in medical diagnosis systems: A case study.

Diagnosing a patient's condition is one of the most important and challenging tasks in medicine. We present a study of the application of collective intelligence in medical diagnosis by applying consensus methods. We compared the accuracy obtained with this method against the diagnostics accuracy reached through the knowledge of a single expert. We used the ontological structures of ten diseases. Two knowledge bases were created by placing five diseases into each knowledge base. We conducted two experiments, one with an empty knowledge base and the other with a populated knowledge base. For both experiments, five experts added and/or eliminated signs/symptoms and diagnostic tests for each disease. After this process, the individual knowledge bases were built based on the output of the consensus methods. In order to perform the evaluation, we compared the number of items for each disease in the agreed knowledge bases against the number of items in the GS (Gold Standard). We identified that, while the number of items in each knowledge base is higher, the consensus level is lower. In all cases, the lowest level of agreement (20%) exceeded the number of signs that are in the GS. In addition, when all experts agreed, the number of items decreased. The use of collective intelligence can be used to increase the consensus of physicians. This is because, by using consensus, physicians can gather more information and knowledge than when obtaining information and knowledge from knowledge bases fed or populated from the knowledge found in the literature, and, at the same time, they can keep updated and collaborate dynamically.

iPixel: a visual content-based and semantic search engine for retrieving digitized mammograms by using collective intelligence.

Nowadays, traditional search engines such as Google, Yahoo and Bing facilitate the retrieval of information in the format of images, but the results are not always useful for the users. This is mainly due to two problems: (1) the semantic keywords are not taken into consideration and (2) it is not always possible to establish a query using the image features. This issue has been covered in different domains in order to develop content-based image retrieval (CBIR) systems. The expert community has focussed their attention on the healthcare domain, where a lot of visual information for medical analysis is available. This paper provides a solution called iPixel Visual Search Engine, which involves semantics and content issues in order to search for digitized mammograms. iPixel offers the possibility of retrieving mammogram features using collective intelligence and implementing a CBIR algorithm. Our proposal compares not only features with similar semantic meaning, but also visual features. In this sense, the comparisons are made in different ways: by the number of regions per image, by maximum and minimum size of regions per image and by average intensity level of each region. iPixel Visual Search Engine supports the medical community in differential diagnoses related to the diseases of the breast. The iPixel Visual Search Engine has been validated by experts in the healthcare domain, such as radiologists, in addition to experts in digital image analysis.