Disease networks and their contribution to disease understanding: A review of their evolution, techniques and data sources.

Over a decade ago, a new discipline called network medicine emerged as an approach to understand human diseases from a network theory point-of-view. Disease networks proved to be an intuitive and powerful way to reveal hidden connections among apparently unconnected biomedical entities such as diseases, physiological processes, signaling pathways, and genes. One of the fields that has benefited most from this improvement is the identification of new opportunities for the use of old drugs, known as drug repurposing. The importance of drug repurposing lies in the high costs and the prolonged time from target selection to regulatory approval of traditional drug development. In this document we analyze the evolution of disease network concept during the last decade and apply a data science pipeline approach to evaluate their functional units. As a result of this analysis, we obtain a list of the most commonly used functional units and the challenges that remain to be solved. This information can be very valuable for the generation of new prediction models based on disease networks.

Supervoxels-Based Histon as a New Alzheimer's Disease Imaging Biomarker.

Alzheimer's disease (AD) represents the prevalent type of dementia in the elderly, and is characterized by the presence of neurofibrillary tangles and amyloid plaques that eventually leads to the loss of neurons, resulting in atrophy in specific brain areas. Although the process of degeneration can be visualized through various modalities of medical imaging and has proved to be a valuable biomarker, the accurate diagnosis of Alzheimer's disease remains a challenge, especially in its early stages. In this paper, we propose a novel classification method for Alzheimer's disease/cognitive normal discrimination in structural magnetic resonance images (MRI), based on the extension of the concept of histons to volumetric images. The proposed method exploits the relationship between grey matter, white matter and cerebrospinal fluid degeneration by means of a segmentation using supervoxels. The calculated histons are then processed for a reduction in dimensionality using principal components analysis (PCA) and the resulting vector is used to train an support vector machine (SVM) classifier. Experimental results using the OASIS-1 database have proven to be a significant improvement compared to a baseline classification made using the pipeline provided by Clinica software.

Profiling Lung Cancer Patients Using Electronic Health Records.

If Electronic Health Records contain a large amount of information about the patient's condition and response to treatment, which can potentially revolutionize the clinical practice, such information is seldom considered due to the complexity of its extraction and analysis. We here report on a first integration of an NLP framework for the analysis of clinical records of lung cancer patients making use of a telephone assistance service of a major Spanish hospital. We specifically show how some relevant data, about patient demographics and health condition, can be extracted; and how some relevant analyses can be performed, aimed at improving the usefulness of the service. We thus demonstrate that the use of EHR texts, and their integration inside a data analysis framework, is technically feasible and worth of further study.

Assessing Time Series Reversibility through Permutation Patterns.

Time irreversibility, i.e., the lack of invariance of the statistical properties of a system under time reversal, is a fundamental property of all systems operating out of equilibrium. Time reversal symmetry is associated with important statistical and physical properties and is related to the predictability of the system generating the time series. Over the past fifteen years, various methods to quantify time irreversibility in time series have been proposed, but these can be computationally expensive. Here, we propose a new method, based on permutation entropy, which is essentially parameter-free, temporally local, yields straightforward statistical tests, and has fast convergence properties. We apply this method to the study of financial time series, showing that stocks and indices present a rich irreversibility dynamics. We illustrate the comparative methodological advantages of our method with respect to a recently proposed method based on visibility graphs, and discuss the implications of our results for financial data analysis and interpretation.

Understanding the role and adoption of artificial intelligence techniques in rheumatology research: An in-depth review of the literature.

The major and upward trend in the number of published research related to rheumatic and musculoskeletal diseases, in which artificial intelligence plays a key role, has exhibited the interest of rheumatology researchers in using these techniques to answer their research questions. In this review, we analyse the original research articles that combine both worlds in a five- year period (2017-2021). In contrast to other published papers on the same topic, we first studied the review and recommendation articles that were published during that period, including up to October 2022, as well as the publication trends. Secondly, we review the published research articles and classify them into one of the following categories: disease identification and prediction, disease classification, patient stratification and disease subtype identification, disease progression and activity, treatment response, and predictors of outcomes. Thirdly, we provide a table with illustrative studies in which artificial intelligence techniques have played a central role in more than twenty rheumatic and musculoskeletal diseases. Finally, the findings of the research articles, in terms of disease and/or data science techniques employed, are highlighted in a discussion. Therefore, the present review aims to characterise how researchers are applying data science techniques in the rheumatology medical field. The most immediate conclusions that can be drawn from this work are: multiple and novel data science techniques have been used in a wide range of rheumatic and musculoskeletal diseases including rare diseases; the sample size and the data type used are heterogeneous, and new technical approaches are expected to arrive in the short-middle term.

DisMaNET: A network-based tool to cross map disease vocabularies.

BACKGROUND AND OBJECTIVES: The growing integration of healthcare sources is improving our understanding of diseases. Cross-mapping resources such as UMLS play a very important role in this area, but their coverage is still incomplete. With the aim to facilitate the integration and interoperability of biological, clinical and literary sources in studies of diseases, we built DisMaNET, a system to cross-map terms from disease vocabularies by leveraging the power and interpretability of network analysis. METHODS: First, we collected and normalized data from 8 disease vocabularies and mapping sources to generate our datasets. Next, we built DisMaNET by integrating the generated datasets into a Neo4j graph database. Then we exploited the query mechanisms of Neo4j to cross-map disease terms of different vocabularies with a relevance score metric and contrasted the results with some state-of-the-art solutions. Finally, we made our system publicly available for its exploitation and evaluation both through a graphical user interface and REST APIs. RESULTS: DisMaNET contains almost half a million nodes and near nine hundred thousand edges, including hierarchical and mapping relationships. Its query capabilities enabled the detection of connections between disease vocabularies that are not present in major mapping sources such as UMLS and the Disease Ontology, even for rare diseases. Furthermore, DisMaNET was capable of obtaining more than 80% of the mappings with UMLS reported in MonDO and DisGeNET, and it was successfully exploited to resolve the missing mappings in the DISNET project. CONCLUSIONS: DisMaNET is a powerful, intuitive and publicly available system to cross-map terms from different disease vocabularies. Our study proves that it is a competitive alternative to existing mapping systems, incorporating the potential of network analysis and the interpretability of the results through a visual interface as its main advantages. Expansion with new sources, versioning and the improvement of the search and scoring algorithms are envisioned as future lines of work.

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.

Leveraging network analysis to evaluate biomedical named entity recognition tools.

The ever-growing availability of biomedical text sources has resulted in a boost in clinical studies based on their exploitation. Biomedical named-entity recognition (bio-NER) techniques have evolved remarkably in recent years and their application in research is increasingly successful. Still, the disparity of tools and the limited available validation resources are barriers preventing a wider diffusion, especially within clinical practice. We here propose the use of omics data and network analysis as an alternative for the assessment of bio-NER tools. Specifically, our method introduces quality criteria based on edge overlap and community detection. The application of these criteria to four bio-NER solutions yielded comparable results to strategies based on annotated corpora, without suffering from their limitations. Our approach can constitute a guide both for the selection of the best bio-NER tool given a specific task, and for the creation and validation of novel approaches.

DISNET: a framework for extracting phenotypic disease information from public sources.

BACKGROUND: Within the global endeavour of improving population health, one major challenge is the identification and integration of medical knowledge spread through several information sources. The creation of a comprehensive dataset of diseases and their clinical manifestations based on information from public sources is an interesting approach that allows one not only to complement and merge medical knowledge but also to increase it and thereby to interconnect existing data and analyse and relate diseases to each other. In this paper, we present DISNET (http://disnet.ctb.upm.es/), a web-based system designed to periodically extract the knowledge from signs and symptoms retrieved from medical databases, and to enable the creation of customisable disease networks. METHODS: We here present the main features of the DISNET system. We describe how information on diseases and their phenotypic manifestations is extracted from Wikipedia and PubMed websites; specifically, texts from these sources are processed through a combination of text mining and natural language processing techniques. RESULTS: We further present the validation of our system on Wikipedia and PubMed texts, obtaining the relevant accuracy. The final output includes the creation of a comprehensive symptoms-disease dataset, shared (free access) through the system's API. We finally describe, with some simple use cases, how a user can interact with it and extract information that could be used for subsequent analyses. DISCUSSION: DISNET allows retrieving knowledge about the signs, symptoms and diagnostic tests associated with a disease. It is not limited to a specific category (all the categories that the selected sources of information offer us) and clinical diagnosis terms. It further allows to track the evolution of those terms through time, being thus an opportunity to analyse and observe the progress of human knowledge on diseases. We further discussed the validation of the system, suggesting that it is good enough to be used to extract diseases and diagnostically-relevant terms. At the same time, the evaluation also revealed that improvements could be introduced to enhance the system's reliability.

Public Health and Epidemiology Informatics: Can Artificial Intelligence Help Future Global Challenges? An Overview of Antimicrobial Resistance and Impact of Climate Change in Disease Epidemiology.

OBJECTIVES: To provide an oveiview of the current application of artificial intelligence (AI) in the field of public health and epidemiology, with a special focus on antimicrobial resistance and the impact of climate change in disease epidemiology. Both topics are of vital importance and were included in the "Ten threats to global health in 2019" report published by the World Health Organization. METHODS: We analysed publications that appeared in the last two years, between January 2017 and October 2018. Papers were searched using Google Scholar with the following keywords: public health, epidemiology, machine learning, data analytics, artificial intelligence, disease surveillance, climate change, antimicrobial resistance, and combinations thereof. Selected articles were organised by theme. RESULTS: In spite of a large interest in AI generated both within and outside the scientific community, and of the many opinions pointing towards the importance of a better use of data in public health, few papers have been published on the selected topics in the last two years. We identify several potential reasons, including the complexity of the integration of heterogeneous data, and the lack of sound and unbiased validation procedures. CONCLUSIONS: As there is a better comprehension of AI and more funding available, artificial intelligence will become not only the centre of attention in informatics, but more importantly the source of innovative solutions for public health.

Automatic extraction and identification of users' responses in Facebook medical quizzes.

BACKGROUND: In the last few years the use of social media in medicine has grown exponentially, providing a new area of research based on the analysis and use of Web 2.0 capabilities. In addition, the use of social media in medical education is a subject of particular interest which has been addressed in several studies. One example of this application is the medical quizzes of The New England Journal of Medicine (NEJM) that regularly publishes a set of questions through their Facebook timeline. OBJECTIVE: We present an approach for the automatic extraction of medical quizzes and their associated answers on a Facebook platform by means of a set of computer-based methods and algorithms. METHODS: We have developed a tool for the extraction and analysis of medical quizzes stored on Facebook timeline at the NEJM Facebook page, based on a set of computer-based methods and algorithms using Java. The system is divided into two main modules: Crawler and Data retrieval. RESULTS: The system was launched on December 31, 2014 and crawled through a total of 3004 valid posts and 200,081 valid comments. The first post was dated on July 23, 2009 and the last one on December 30, 2014. 285 quizzes were analyzed with 32,780 different users providing answers to the aforementioned quizzes. Of the 285 quizzes, patterns were found in 261 (91.58%). From these 261 quizzes where trends were found, we saw that users follow trends of incorrect answers in 13 quizzes and trends of correct answers in 248. CONCLUSIONS: This tool is capable of automatically identifying the correct and wrong answers to a quiz provided on Facebook posts in a text format to a quiz, with a small rate of false negative cases and this approach could be applicable to the extraction and analysis of other sources after including some adaptations of the information on the Internet.