Luca Toldo

Extraction of potential adverse drug events from medical case reports

AbstractThe sheer amount of information about potential adverse drug events publishedin medical case reports pose major challenges for drug safety experts toperform timely monitoring. Efficient strategies for identification andextraction of information about potential adverse drug events fromfree‐text resources are needed to support pharmacovigilance researchand pharmaceutical decision making. Therefore, this work focusses on theadaptation of a machine learning‐based system for the identificationand extraction of potential adverse drug event relations from MEDLINE casereports. It relies on a high quality corpus that was manually annotatedusing an ontology‐driven methodology. Qualitative evaluation of thesystem showed robust results. An experiment with large scale relationextraction from MEDLINE delivered under‐identified potential adversedrug events not reported in drug monographs. Overall, this approach providesa scalable auto‐assistance platform for drug safety professionals toautomatically collect potential adverse drug events communicated asfree‐text data.

Development of a benchmark corpus to support the automatic extraction of drug-related adverse effects from medical case reports

A significant amount of information about drug-related safety issues such as adverse effects are published in medical case reports that can only be explored by human readers due to their unstructured nature. The work presented here aims at generating a systematically annotated corpus that can support the development and validation of methods for the automatic extraction of drug-related adverse effects from medical case reports. The documents are systematically double annotated in various rounds to ensure consistent annotations. The annotated documents are finally harmonized to generate representative consensus annotations. In order to demonstrate an example use case scenario, the corpus was employed to train and validate models for the classification of informative against the non-informative sentences. A Maximum Entropy classifier trained with simple features and evaluated by 10-fold cross-validation resulted in the F₁ score of 0.70 indicating a potential useful application of the corpus.

BioCreative III interactive task: an overview

BackgroundThe BioCreative challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems applied to the biological domain. The biocurator community, as an active user of biomedical literature, provides a diverse and engaged end user group for text mining tools. Earlier BioCreative challenges involved many text mining teams in developing basic capabilities relevant to biological curation, but they did not address the issues of system usage, insertion into the workflow and adoption by curators. Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to address the utility and usability of text mining tools for real-life biocuration tasks. To support the aims of the IAT in BC-III, involvement of both developers and end users was solicited, and the development of a user interface to address the tasks interactively was requested.ResultsA User Advisory Group (UAG) actively participated in the IAT design and assessment. The task focused on gene normalization (identifying gene mentions in the article and linking these genes to standard database identifiers), gene ranking based on the overall importance of each gene mentioned in the article, and gene-oriented document retrieval (identifying full text papers relevant to a selected gene). Six systems participated and all processed and displayed the same set of articles. The articles were selected based on content known to be problematic for curation, such as ambiguity of gene names, coverage of multiple genes and species, or introduction of a new gene name. Members of the UAG curated three articles for training and assessment purposes, and each member was assigned a system to review. A questionnaire related to the interface usability and task performance (as measured by precision and recall) was answered after systems were used to curate articles. Although the limited number of articles analyzed and users involved in the IAT experiment precluded rigorous quantitative analysis of the results, a qualitative analysis provided valuable insight into some of the problems encountered by users when using the systems. The overall assessment indicates that the system usability features appealed to most users, but the system performance was suboptimal (mainly due to low accuracy in gene normalization). Some of the issues included failure of species identification and gene name ambiguity in the gene normalization task leading to an extensive list of gene identifiers to review, which, in some cases, did not contain the relevant genes. The document retrieval suffered from the same shortfalls. The UAG favored achieving high performance (measured by precision and recall), but strongly recommended the addition of features that facilitate the identification of correct gene and its identifier, such as contextual information to assist in disambiguation.DiscussionThe IAT was an informative exercise that advanced the dialog between curators and developers and increased the appreciation of challenges faced by each group. A major conclusion was that the intended users should be actively involved in every phase of software development, and this will be strongly encouraged in future tasks. The IAT Task provides the first steps toward the definition of metrics and functional requirements that are necessary for designing a formal evaluation of interactive curation systems in the BioCreative IV challenge.

OAE: The Ontology of Adverse Events

BackgroundA medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health.DescriptionThe Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA.ConclusionOAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e.g., vaccinee age) important for determining their clinical outcomes.

Automatic detection of adverse events to predict drug label changes using text and data mining techniques

The aim of this study was to assess the impact of automatically detected adverse event signals from text and open‐source data on the prediction of drug label changes.

Toxicology ontology perspectives.

The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

Knowledge Retrieval from PubMed Abstracts and Electronic Medical Records with the Multiple Sclerosis Ontology

Background In order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS). Methods The MS Ontology was created using scientific literature and expert review under the Protégé OWL environment. We developed a dictionary with semantic synonyms and translations to different languages for mining EMR. The MS Ontology was integrated with other ontologies and dictionaries (diseases/comorbidities, gene/protein, pathways, drug) into the text-mining tool SCAIView. We analyzed the EMRs from 624 patients with MS using the MS ontology dictionary in order to identify drug usage and comorbidities in MS. Testing competency questions and functional evaluation using F statistics further validated the usefulness of MS ontology. Results Validation of the lexicalized ontology by means of named entity recognition-based methods showed an adequate performance (F score = 0.73). The MS Ontology retrieved 80% of the genes associated with MS from scientific abstracts and identified additional pathways targeted by approved disease-modifying drugs (e.g. apoptosis pathways associated with mitoxantrone, rituximab and fingolimod). The analysis of the EMR from patients with MS identified current usage of disease modifying drugs and symptomatic therapy as well as comorbidities, which are in agreement with recent reports. Conclusion The MS Ontology provides a semantic framework that is able to automatically extract information from both scientific literature and EMR from patients with MS, revealing new pathogenesis insights as well as new clinical information.

Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis

BackgroundMultiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and bodys own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted.ResultsWe presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved.ConclusionsThe presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms.

Challenges in mining the literature for chemical information

Chemical information extracted from the literature is of immense value for the pharmaceutical and chemical industries in many areas, including supporting drug discovery, manufacturing processes, or intellectual property protection. However, the exponential growth of the chemical literature has made it increasingly difficult for researchers to find the information they need within a reasonable time-frame. In order to address this issue, a large number of text mining approaches have been developed that can extract chemical information from different types of literature. But the lack of a single universal standard for chemical structure and nomenclature representation has posed significant challenges in mining the chemical information. Hence, a review on the current state of chemical text mining, problems confronted, solutions available, and future prospectus is presented.

A 2012 Workshop: Vaccine and Drug Ontology in the Study of Mechanism and Effect (VDOSME 2012)

Vaccines and drugs have contributed to dramatic improvements in public health worldwide. Over the last decade, there have been efforts in developing biomedical ontologies that represent various areas associated with vaccines and drugs. These ontologies combined with existing health and clinical terminology systems (e.g., SNOMED, RxNorm, NDF-RT, MedDRA, VO, OAE, and AERO) could play significant roles on clinical and translational research. The first “Vaccine and Drug Ontology in the Study of Mechanism and Effect” workshop (VDOSME 2012) provided a platform for discussing problems and solutions in the development and application of biomedical ontologies in representing and analyzing vaccines/drugs, vaccine/drug administrations, vaccine/drug-induced immune responses (including positive host responses and adverse events), and similar topics. The workshop covered two main areas: (i) ontologies of vaccines, of drugs, and of studies thereof; and (ii) analysis of administration, mechanism and effect in terms of representations based on such ontologies. Six full-length papers included in this thematic issue focus on ontology representation and time analysis of vaccine/drug administration and host responses (including positive immune responses and adverse events), vaccine and drug adverse event text mining, and ontology-based Semantic Web applications. The workshop, together with the follow-up activities and personal meetings, provided a wonderful platform for the researchers and scientists in the vaccine and drug communities to demonstrate research progresses, share ideas, address questions, and promote collaborations for better representation and analysis of vaccine and drug-related terminologies and clinical and research data.