Adverse drug reaction extraction on electronic health records written in Spanish

148 p.This work focuses on the automatic extraction of Adverse Drug Reactions (ADRs) in Electronic HealthRecords (EHRs). That is, extracting a response to a medicine which is noxious and unintended and whichoccurs at doses normally used. From Natural Language Processing (NLP) perspective, this wasapproached as a relation extraction task in which the drug is the causative agent of a disease, sign orsymptom, that is, the adverse reaction.ADR extraction from EHRs involves major challenges. First, ADRs are rare events. That is, relationsbetween drugs and diseases found in an EHR are seldom ADRs (are often unrelated or, instead, related astreatment). This implies the inference from samples with skewed class distribution. Second, EHRs arewritten by experts often under time pressure, employing both rich medical jargon together with colloquialexpressions (not always grammatical) and it is not infrequent to find misspells and both standard andnon-standard abbreviations. All this leads to a high lexical variability.We explored several ADR detection algorithms and representations to characterize the ADR candidates.In addition, we have assessed the tolerance of the ADR detection model to external noise such as theincorrect detection of implied medical entities implied in the ADR extraction, i.e. drugs and diseases. Westtled the first steps on ADR extraction in Spanish using a corpus of real EHRs

Information retrieval and text mining technologies for chemistry

Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.A.V. and M.K. acknowledge funding from the European Community’s Horizon 2020 Program (project reference: 654021 - OpenMinted). M.K. additionally acknowledges the Encomienda MINETAD-CNIO as part of the Plan for the Advancement of Language Technology. O.R. and J.O. thank the Foundation for Applied Medical Research (FIMA), University of Navarra (Pamplona, Spain). This work was partially funded by Consellería de Cultura, Educación e Ordenación Universitaria (Xunta de Galicia), and FEDER (European Union), and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). We thank Iñigo Garciá -Yoldi for useful feedback and discussions during the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Use of state sequence analysis in pharmacoepidemiology: A tutorial

none6noWhile state sequence analysis (SSA) has been long used in social sciences, its use in pharmacoepidemiology is still in its infancy. Indeed, this technique is relatively easy to use, and its intrinsic visual nature may help investigators to untangle the latent information within prescription data, facilitating the individuation of specific patterns and possible inappropriate use of medications. In this paper, we provide an educational primer of the most important learning concepts and methods of SSA, including measurement of dissimilarities between sequences, the application of clustering methods to identify sequence patterns, the use of complexity measures for sequence patterns, the graphical visualization of sequences, and the use of SSA in predictive models. As a worked example, we present an application of SSA to opioid prescription patterns in patients with non-cancer pain, using real-world data from Italy. We show how SSA allows the identification of patterns in prescriptions in these data that might not be evident using standard statistical approaches and how these patterns are associated with future discontinuation of opioid therapy.openVanoli J.; Nava C.R.; Airoldi C.; Ucciero A.; Salvi V.; Barone-Adesi F.Vanoli, J.; Nava, C. R.; Airoldi, C.; Ucciero, A.; Salvi, V.; Barone-Adesi, F

Drug Target Interaction Prediction Using Machine Learning Techniques – A Review

Drug discovery is a key process, given the rising and ubiquitous demand for medication to stay in good shape right through the course of one’s life. Drugs are small molecules that inhibit or activate the function of a protein, offering patients a host of therapeutic benefits. Drug design is the inventive process of finding new medication, based on targets or proteins. Identifying new drugs is a process that involves time and money. This is where computer-aided drug design helps cut time and costs. Drug design needs drug targets that are a protein and a drug compound, with which the interaction between a drug and a target is established. Interaction, in this context, refers to the process of discovering protein binding sites, which are protein pockets that bind with drugs. Pockets are regions on a protein macromolecule that bind to drug molecules. Researchers have been at work trying to determine new Drug Target Interactions (DTI) that predict whether or not a given drug molecule will bind to a target. Machine learning (ML) techniques help establish the interaction between drugs and their targets, using computer-aided drug design. This paper aims to explore ML techniques better for DTI prediction and boost future research. Qualitative and quantitative analyses of ML techniques show that several have been applied to predict DTIs, employing a range of classifiers. Though DTI prediction improves with negative drug target pairs (DTP), the lack of true negative DTPs has led to the use a particular dataset of drugs and targets. Using dynamic DTPs improves DTI prediction. Little attention has so far been paid to developing a new classifier for DTI classification, and there is, unquestionably, a need for better ones

Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning

BACKGROUND: Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. OBJECTIVE: To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. METHODS: We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. RESULTS: Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. CONCLUSIONS: It shows that classical learning models (SVM) remains advantageous over deep learning models (RNN variants) for clinical relation identification, especially for long-distance intersentential relations. However, RNNs demonstrate a great potential of significant improvement if more training data become available. Our work is an important step toward mining EHRs to improve the efficacy of drug safety surveillance. Most importantly, the annotated data used in this study will be made publicly available, which will further promote drug safety research in the community

Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems

A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus, characterizing such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein–protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: (i) sampling of the possible binding modes between the interacting molecules and (ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein–protein interactions, or providing modeled structural data for drug discovery targeting protein–protein interactions.Spanish Ministry of Economy grant number BIO2016-79960-R; D.B.B. is supported by a predoctoral fellowship from CONACyT; M.R. is supported by an FPI fellowship from the Severo Ochoa program. We are grateful to the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

Visual Analytics for Performing Complex Tasks with Electronic Health Records

Electronic health record systems (EHRs) facilitate the storage, retrieval, and sharing of patient health data; however, the availability of data does not directly translate to support for tasks that healthcare providers encounter every day. In recent years, healthcare providers employ a large volume of clinical data stored in EHRs to perform various complex data-intensive tasks. The overwhelming volume of clinical data stored in EHRs and a lack of support for the execution of EHR-driven tasks are, but a few problems healthcare providers face while working with EHR-based systems. Thus, there is a demand for computational systems that can facilitate the performance of complex tasks that involve the use and working with the vast amount of data stored in EHRs. Visual analytics (VA) offers great promise in handling such information overload challenges by integrating advanced analytics techniques with interactive visualizations. The user-controlled environment that VA systems provide allows healthcare providers to guide the analytics techniques on analyzing and managing EHR data through interactive visualizations. The goal of this research is to demonstrate how VA systems can be designed systematically to support the performance of complex EHR-driven tasks. In light of this, we present an activity and task analysis framework to analyze EHR-driven tasks in the context of interactive visualization systems. We also conduct a systematic literature review of EHR-based VA systems and identify the primary dimensions of the VA design space to evaluate these systems and identify the gaps. Two novel EHR-based VA systems (SUNRISE and VERONICA) are then designed to bridge the gaps. SUNRISE incorporates frequent itemset mining, extreme gradient boosting, and interactive visualizations to allow users to interactively explore the relationships between laboratory test results and a disease outcome. The other proposed system, VERONICA, uses a representative set of supervised machine learning techniques to find the group of features with the strongest predictive power and make the analytic results accessible through an interactive visual interface. We demonstrate the usefulness of these systems through a usage scenario with acute kidney injury using large provincial healthcare databases from Ontario, Canada, stored at ICES

AliClu - Temporal sequence alignment for clustering longitudinal clinical data

The authors acknowledge funding the Portuguese Foundation for Science and Technology (Fundação para a Ciência e a Tecnologia - FCT) under contracts INESC-ID (UID/CEC/50021/2019) and IT (UID/EEA/50008/2019), projects PREDICT (PTDC/CCI-CIF/29877/2017), PERSEIDS (PTDC/EMS-SIS/0642/2014) and NEUROCLINOMICS2 (PTDC/EEI-SII/1937/2014). The funders had no role in the design of the study, collection, analysis and interpretation of data, or writing the manuscript.BACKGROUND: Patient stratification is a critical task in clinical decision making since it can allow physicians to choose treatments in a personalized way. Given the increasing availability of electronic medical records (EMRs) with longitudinal data, one crucial problem is how to efficiently cluster the patients based on the temporal information from medical appointments. In this work, we propose applying the Temporal Needleman-Wunsch (TNW) algorithm to align discrete sequences with the transition time information between symbols. These symbols may correspond to a patient's current therapy, their overall health status, or any other discrete state. The transition time information represents the duration of each of those states. The obtained TNW pairwise scores are then used to perform hierarchical clustering. To find the best number of clusters and assess their stability, a resampling technique is applied. RESULTS: We propose the AliClu, a novel tool for clustering temporal clinical data based on the TNW algorithm coupled with clustering validity assessments through bootstrapping. The AliClu was applied for the analysis of the rheumatoid arthritis EMRs obtained from the Portuguese database of rheumatologic patient visits (Reuma.pt). In particular, the AliClu was used for the analysis of therapy switches, which were coded as letters corresponding to biologic drugs and included their durations before each change occurred. The obtained optimized clusters allow one to stratify the patients based on their temporal therapy profiles and to support the identification of common features for those groups. CONCLUSIONS: The AliClu is a promising computational strategy to analyse longitudinal patient data by providing validated clusters and by unravelling the patterns that exist in clinical outcomes. Patient stratification is performed in an automatic or semi-automatic way, allowing one to tune the alignment, clustering, and validation parameters. The AliClu is freely available at https://github.com/sysbiomed/AliClu.publishersversionpublishe

Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome

Identifying genetic factors responsible for serious adverse drug reaction (SADR) is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might share a common mechanism by targeting unexpectedly the same SADR-mediating protein. Hence we propose an approach of identifying the common SADR-targets through constructing and mining an in silico chemical-protein interactome (CPI), a matrix of binding strengths among 162 drug molecules known to cause at least one type of SADR and 845 proteins. Drugs sharing the same SADR outcome were also found to possess similarities in their CPI profiles towards this 845 protein set. This methodology identified the candidate gene of sulfonamide-induced toxic epidermal necrolysis (TEN): all nine sulfonamides that cause TEN were found to bind strongly to MHC I (Cw*4), whereas none of the 17 control drugs that do not cause TEN were found to bind to it. Through an insight into the CPI, we found the Y116S substitution of MHC I (B*5703) enhances the unexpected binding of abacavir to its antigen presentation groove, which explains why B*5701, not B*5703, is the risk allele of abacavir-induced hypersensitivity. In conclusion, SADR targets and the patient-specific off-targets could be identified through a systematic investigation of the CPI, generating important hypotheses for prospective experimental validation of the candidate genes