Genomic and proteomic biomarker landscape in clinical trials.

The use of molecular biomarkers to support disease diagnosis, monitor its progression, and guide drug treatment has gained traction in the last decades. While only a dozen biomarkers have been approved for their exploitation in the clinic by the FDA, many more are evaluated in the context of translational research and clinical trials. Furthermore, the information on which biomarkers are measured, for which purpose, and in relation to which conditions are not readily accessible: biomarkers used in clinical studies available through resources such as ClinicalTrials.gov are described as free text, posing significant challenges in finding, analyzing, and processing them by both humans and machines. We present a text mining strategy to identify proteomic and genomic biomarkers used in clinical trials and classify them according to the methodologies by which they are measured. We find more than 3000 biomarkers used in the context of 2600 diseases. By analyzing this dataset, we uncover patterns of use of biomarkers across therapeutic areas over time, including the biomarker type and their specificity. These data are made available at the Clinical Biomarker App at https://www.disgenet.org/biomarkers/, a new portal that enables the exploration of biomarkers extracted from the clinical studies available at ClinicalTrials.gov and enriched with information from the scientific literature. The App features several metrics that assess the specificity of the biomarkers, facilitating their selection and prioritization. Overall, the Clinical Biomarker App is a valuable and timely resource about clinical biomarkers, to accelerate biomarker discovery, development, and application.

Exploring the Association of Cancer and Depression in Electronic Health Records: Combining Encoded Diagnosis and Mining Free-Text Clinical Notes.

BACKGROUND: A cancer diagnosis is a source of psychological and emotional stress, which are often maintained for sustained periods of time that may lead to depressive disorders. Depression is one of the most common psychological conditions in patients with cancer. According to the Global Cancer Observatory, breast and colorectal cancers are the most prevalent cancers in both sexes and across all age groups in Spain. OBJECTIVE: This study aimed to compare the prevalence of depression in patients before and after the diagnosis of breast or colorectal cancer, as well as to assess the usefulness of the analysis of free-text clinical notes in 2 languages (Spanish or Catalan) for detecting depression in combination with encoded diagnoses. METHODS: We carried out an analysis of the electronic health records from a general hospital by considering the different sources of clinical information related to depression in patients with breast and colorectal cancer. This analysis included ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis codes and unstructured information extracted by mining free-text clinical notes via natural language processing tools based on Systematized Nomenclature of Medicine Clinical Terms that mentions symptoms and drugs used for the treatment of depression. RESULTS: We observed that the percentage of patients diagnosed with depressive disorders significantly increased after cancer diagnosis in the 2 types of cancer considered-breast and colorectal cancers. We managed to identify a higher number of patients with depression by mining free-text clinical notes than the group selected exclusively on ICD-9-CM codes, increasing the number of patients diagnosed with depression by 34.8% (441/1269). In addition, the number of patients with depression who received chemotherapy was higher than those who did not receive this treatment, with significant differences (P<.001). CONCLUSIONS: This study provides new clinical evidence of the depression-cancer comorbidity and supports the use of natural language processing for extracting and analyzing free-text clinical notes from electronic health records, contributing to the identification of additional clinical data that complements those provided by coded data to improve the management of these patients.

The eTRANSAFE Project on Translational Safety Assessment through Integrative Knowledge Management: Achievements and Perspectives.

eTRANSAFE is a research project funded within the Innovative Medicines Initiative (IMI), which aims at developing integrated databases and computational tools (the eTRANSAFE ToxHub) that support the translational safety assessment of new drugs by using legacy data provided by the pharmaceutical companies that participate in the project. The project objectives include the development of databases containing preclinical and clinical data, computational systems for translational analysis including tools for data query, analysis and visualization, as well as computational models to explain and predict drug safety events.

Evaluating Behavioral and Linguistic Changes During Drug Treatment for Depression Using Tweets in Spanish: Pairwise Comparison Study.

BACKGROUND: Depressive disorders are the most common mental illnesses, and they constitute the leading cause of disability worldwide. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for the treatment of depressive disorders. Some people share information about their experiences with antidepressants on social media platforms such as Twitter. Analysis of the messages posted by Twitter users under SSRI treatment can yield useful information on how these antidepressants affect users' behavior. OBJECTIVE: This study aims to compare the behavioral and linguistic characteristics of the tweets posted while users were likely to be under SSRI treatment, in comparison to the tweets posted by the same users when they were less likely to be taking this medication. METHODS: In the first step, the timelines of Twitter users mentioning SSRI antidepressants in their tweets were selected using a list of 128 generic and brand names of SSRIs. In the second step, two datasets of tweets were created, the in-treatment dataset (made up of the tweets posted throughout the 30 days after mentioning an SSRI) and the unknown-treatment dataset (made up of tweets posted more than 90 days before or more than 90 days after any tweet mentioning an SSRI). For each user, the changes in behavioral and linguistic features between the tweets classified in these two datasets were analyzed. 186 users and their timelines with 668,842 tweets were finally included in the study. RESULTS: The number of tweets generated per day by the users when they were in treatment was higher than it was when they were in the unknown-treatment period (P=.001). When the users were in treatment, the mean percentage of tweets posted during the daytime (from 8 AM to midnight) increased in comparison to the unknown-treatment period (P=.002). The number of characters and words per tweet was higher when the users were in treatment (P=.03 and P=.02, respectively). Regarding linguistic features, the percentage of pronouns that were first-person singular was higher when users were in treatment (P=.008). CONCLUSIONS: Behavioral and linguistic changes have been detected when users with depression are taking antidepressant medication. These features can provide interesting insights for monitoring the evolution of this disease, as well as offering additional information related to treatment adherence. This information may be especially useful in patients who are receiving long-term treatments such as people suffering from depression.

Clinical-Based and Expert Selection of Terms Related to Depression for Twitter Streaming and Language Analysis.

People use language to express their thoughts and feelings, unveiling important aspects of their psychological traits and social interactions. Although there are several studies describing methodologies to create a collection of words in English related to depression and other conditions, in most of them the selection of words is not clinical or expert based. The objective of this study is twofold: firstly, to introduce a comprehensive collection of Spanish words commonly used by patients suffering from depression, which will be available as a free open source for research purposes (GitHub), and secondly, to study the usefulness of this collection of words in identifying social media posts that could be indicative of patients suffering from depression. The level of agreement among medical doctors to determine the best words that should be used to select tweets related to depression was low. This finding may be due to the complexity of depression and the extraordinary diversity in the way people express themselves when describing their illness. It is critical to perform a thorough analysis of the specific language used in each condition, before deciding the best words to be used for filtering the tweets in each disease. As our study shows, the words supposedly more linked to depression are very common words used in other contexts, and consequently less specific for detecting depressive users. In addition, grammatical gender forms should be considered when analysing some languages such as Spanish.

The DisGeNET knowledge platform for disease genomics: 2019 update.

One of the most pressing challenges in genomic medicine is to understand the role played by genetic variation in health and disease. Thanks to the exploration of genomic variants at large scale, hundreds of thousands of disease-associated loci have been uncovered. However, the identification of variants of clinical relevance is a significant challenge that requires comprehensive interrogation of previous knowledge and linkage to new experimental results. To assist in this complex task, we created DisGeNET (http://www.disgenet.org/), a knowledge management platform integrating and standardizing data about disease associated genes and variants from multiple sources, including the scientific literature. DisGeNET covers the full spectrum of human diseases as well as normal and abnormal traits. The current release covers more than 24 000 diseases and traits, 17 000 genes and 117 000 genomic variants. The latest developments of DisGeNET include new sources of data, novel data attributes and prioritization metrics, a redesigned web interface and recently launched APIs. Thanks to the data standardization, the combination of expert curated information with data automatically mined from the scientific literature, and a suite of tools for accessing its publicly available data, DisGeNET is an interoperable resource supporting a variety of applications in genomic medicine and drug R&D.

Detecting Signs of Depression in Tweets in Spanish: Behavioral and Linguistic Analysis.

BACKGROUND: Mental disorders have become a major concern in public health, and they are one of the main causes of the overall disease burden worldwide. Social media platforms allow us to observe the activities, thoughts, and feelings of people's daily lives, including those of patients suffering from mental disorders. There are studies that have analyzed the influence of mental disorders, including depression, in the behavior of social media users, but they have been usually focused on messages written in English. OBJECTIVE: The study aimed to identify the linguistic features of tweets in Spanish and the behavioral patterns of Twitter users who generate them, which could suggest signs of depression. METHODS: This study was developed in 2 steps. In the first step, the selection of users and the compilation of tweets were performed. A total of 3 datasets of tweets were created, a depressive users dataset (made up of the timeline of 90 users who explicitly mentioned that they suffer from depression), a depressive tweets dataset (a manual selection of tweets from the previous users, which included expressions indicative of depression), and a control dataset (made up of the timeline of 450 randomly selected users). In the second step, the comparison and analysis of the 3 datasets of tweets were carried out. RESULTS: In comparison with the control dataset, the depressive users are less active in posting tweets, doing it more frequently between 23:00 and 6:00 (P<.001). The percentage of nouns used by the control dataset almost doubles that of the depressive users (P<.001). By contrast, the use of verbs is more common in the depressive users dataset (P<.001). The first-person singular pronoun was by far the most used in the depressive users dataset (80%), and the first- and the second-person plural pronouns were the least frequent (0.4% in both cases), this distribution being different from that of the control dataset (P<.001). Emotions related to sadness, anger, and disgust were more common in the depressive users and depressive tweets datasets, with significant differences when comparing these datasets with the control dataset (P<.001). As for negation words, they were detected in 34% and 46% of tweets in among depressive users and in depressive tweets, respectively, which are significantly different from the control dataset (P<.001). Negative polarity was more frequent in the depressive users (54%) and depressive tweets (65%) datasets than in the control dataset (43.5%; P<.001). CONCLUSIONS: Twitter users who are potentially suffering from depression modify the general characteristics of their language and the way they interact on social media. On the basis of these changes, these users can be monitored and supported, thus introducing new opportunities for studying depression and providing additional health care services to people with this disorder.

Comorbidity4j: a tool for interactive analysis of disease comorbidities over large patient datasets.

SUMMARY: Pushed by the growing availability of Electronic Health Records for data mining, the identification of relevant patterns of co-occurring diseases over a population of individuals-referred to as comorbidity analysis-has become a common practice due to its great impact on life expectancy, quality of life and healthcare costs. In this scenario, the availability of scalable, easy-to-use software frameworks tailored to support the study of comorbidities over large datasets of patients is essential. We introduce Comorbidity4j, an open-source Java tool to perform systematic analyses of comorbidities by generating interactive Web visualizations to explore and refine results. Comorbidity4j processes user-provided clinical data by identifying significant disease co-occurrences and computing a comprehensive set of comorbidity indices. Patients can be stratified by sex, age and user-defined criteria. Comorbidity4j supports the analysis of the temporal directionality and the sex ratio of diseases. The incremental upload and validation of clinical input data and the customization of comorbidity analyses are performed by an interactive Web interface. With a Web browser, the results of such analyses can be filtered with respect to comorbidity indexes and disease names and explored by means of heat maps and network charts of disease associations. Comorbidity4j is optimized to efficiently process large datasets of clinical data. Besides a software tool for local execution, we provide Comorbidity4j as a Web service to enable users to perform online comorbidity analyses. AVAILABILITY AND IMPLEMENTATION: Doc: http://comorbidity4j.readthedocs.io/; Source code: https://github.com/fra82/comorbidity4j, Web tool: http://comorbidity.eu/comorbidity4web/.