Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

SemClinBr -- a multi institutional and multi specialty semantically annotated corpus for Portuguese clinical NLP tasks

The high volume of research focusing on extracting patient's information from electronic health records (EHR) has led to an increase in the demand for annotated corpora, which are a very valuable resource for both the development and evaluation of natural language processing (NLP) algorithms. The absence of a multi-purpose clinical corpus outside the scope of the English language, especially in Brazilian Portuguese, is glaring and severely impacts scientific progress in the biomedical NLP field. In this study, we developed a semantically annotated corpus using clinical texts from multiple medical specialties, document types, and institutions. We present the following: (1) a survey listing common aspects and lessons learned from previous research, (2) a fine-grained annotation schema which could be replicated and guide other annotation initiatives, (3) a web-based annotation tool focusing on an annotation suggestion feature, and (4) both intrinsic and extrinsic evaluation of the annotations. The result of this work is the SemClinBr, a corpus that has 1,000 clinical notes, labeled with 65,117 entities and 11,263 relations, and can support a variety of clinical NLP tasks and boost the EHR's secondary use for the Portuguese language

Specializing for predicting obesity and its co-morbidities

AbstractWe present specializing, a method for combining classifiers for multi-class classification. Specializing trains one specialist classifier per class and utilizes each specialist to distinguish that class from all others in a one-versus-all manner. It then supplements the specialist classifiers with a catch-all classifier that performs multi-class classification across all classes. We refer to the resulting combined classifier as a specializing classifier.We develop specializing to classify 16 diseases based on discharge summaries. For each discharge summary, we aim to predict whether each disease is present, absent, or questionable in the patient, or unmentioned in the discharge summary. We treat the classification of each disease as an independent multi-class classification task. For each disease, we develop one specialist classifier for each of the present, absent, questionable, and unmentioned classes; we supplement these specialist classifiers with a catch-all classifier that encompasses all of the classes for that disease. We evaluate specializing on each of the 16 diseases and show that it improves significantly over voting and stacking when used for multi-class classification on our data

Doctor of Philosophy

dissertationThe primary objective of cancer registries is to capture clinical care data of cancer populations and aid in prevention, allow early detection, determine prognosis, and assess quality of various treatments and interventions. Furthermore, the role of cancer registries is paramount in supporting cancer epidemiological studies and medical research. Existing cancer registries depend mostly on humans, known as Cancer Tumor Registrars (CTRs), to conduct manual abstraction of the electronic health records to find reportable cancer cases and extract other data elements required for regulatory reporting. This is often a time-consuming and laborious task prone to human error affecting quality, completeness and timeliness of cancer registries. Central state cancer registries take responsibility for consolidating data received from multiple sources for each cancer case and to assign the most accurate information. The Utah Cancer Registry (UCR) at the University of Utah, for instance, leads and oversees more than 70 cancer treatment facilities in the state of Utah to collect data for each diagnosed cancer case and consolidate multiple sources of information.Although software tools helping with the manual abstraction process exist, they mainly focus on cancer case findings based on pathology reports and do not support automatic extraction of other data elements such as TNM cancer stage information, an important prognostic factor required before initiating clinical treatment. In this study, I present novel applications of natural language processing (NLP) and machine learning (ML) to automatically extract clinical and pathological TNM stage information from unconsolidated clinical records of cancer patients available at the central Utah Cancer Registry. To further support CTRs in their manual efforts, I demonstrate a new approach based on machine learning to consolidate TNM stages from multiple records at the patient level

Distributional Semantic Models for Clinical Text Applied to Health Record Summarization

As information systems in the health sector are becoming increasingly computerized, large amounts of care-related information are being stored electronically. In hospitals clinicians continuously document treatment and care given to patients in electronic health record (EHR) systems. Much of the information being documented is in the form of clinical notes, or narratives, containing primarily unstructured free-text information. For each care episode, clinical notes are written on a regular basis, ending with a discharge summary that basically summarizes the care episode. Although EHR systems are helpful for storing and managing such information, there is an unrealized potential in utilizing this information for smarter care assistance, as well as for secondary purposes such as research and education. Advances in clinical language processing are enabling computers to assist clinicians in their interaction with the free-text information documented in EHR systems. This includes assisting in tasks like query-based search, terminology development, knowledge extraction, translation, and summarization. This thesis explores various computerized approaches and methods aimed at enabling automated semantic textual similarity assessment and information extraction based on the free-text information in EHR systems. The focus is placed on the task of (semi-)automated summarization of the clinical notes written during individual care episodes. The overall theme of the presented work is to utilize resource-light approaches and methods, circumventing the need to manually develop knowledge resources or training data. Thus, to enable computational semantic textual similarity assessment, word distribution statistics are derived from large training corpora of clinical free text and stored as vector-based representations referred to as distributional semantic models. Also resource-light methods are explored in the task of performing automatic summarization of clinical freetext information, relying on semantic textual similarity assessment. Novel and experimental methods are presented and evaluated that focus on: a) distributional semantic models trained in an unsupervised manner from statistical information derived from large unannotated clinical free-text corpora; b) representing and computing semantic similarities between linguistic items of different granularity, primarily words, sentences and clinical notes; and c) summarizing clinical free-text information from individual care episodes. Results are evaluated against gold standards that reflect human judgements. The results indicate that the use of distributional semantics is promising as a resource-light approach to automated capturing of semantic textual similarity relations from unannotated clinical text corpora. Here it is important that the semantics correlate with the clinical terminology, and with various semantic similarity assessment tasks. Improvements over classical approaches are achieved when the underlying vector-based representations allow for a broader range of semantic features to be captured and represented. These are either distributed over multiple semantic models trained with different features and training corpora, or use models that store multiple sense-vectors per word. Further, the use of structured meta-level information accompanying care episodes is explored as training features for distributional semantic models, with the aim of capturing semantic relations suitable for care episode-level information retrieval. Results indicate that such models performs well in clinical information retrieval. It is shown that a method called Random Indexing can be modified to construct distributional semantic models that capture multiple sense-vectors for each word in the training corpus. This is done in a way that retains the original training properties of the Random Indexing method, by being incremental, scalable and distributional. Distributional semantic models trained with a framework called Word2vec, which relies on the use of neural networks, outperform those trained using the classic Random Indexing method in several semantic similarity assessment tasks, when training is done using comparable parameters and the same training corpora. Finally, several statistical features in clinical text are explored in terms of their ability to indicate sentence significance in a text summary generated from the clinical notes. This includes the use of distributional semantics to enable case-based similarity assessment, where cases are other care episodes and their “solutions”, i.e., discharge summaries. A type of manual evaluation is performed, where human experts rates the different aspects of the summaries using a evaluation scheme/tool. In addition, the original clinician-written discharge summaries are explored as gold standard for the purpose of automated evaluation. Evaluation shows a high correlation between manual and automated evaluation, suggesting that such a gold standard can function as a proxy for human evaluations. --- This thesis has been published jointly with Norwegian University of Science and Technology, Norway and University of Turku, Finland.This thesis has beenpublished jointly with Norwegian University of Science and Technology, Norway.Siirretty Doriast

A modular, open-source information extraction framework for identifying clinical concepts and processes of care in clinical narratives

In this thesis, a synthesis is presented of the knowledge models required by clinical informa- tion systems that provide decision support for longitudinal processes of care. Qualitative research techniques and thematic analysis are novelly applied to a systematic review of the literature on the challenges in implementing such systems, leading to the development of an original conceptual framework. The thesis demonstrates how these process-oriented systems make use of a knowledge base derived from workflow models and clinical guidelines, and argues that one of the major barriers to implementation is the need to extract explicit and implicit information from diverse resources in order to construct the knowledge base. Moreover, concepts in both the knowledge base and in the electronic health record (EHR) must be mapped to a common ontological model. However, the majority of clinical guideline information remains in text form, and much of the useful clinical information residing in the EHR resides in the free text fields of progress notes and laboratory reports. In this thesis, it is shown how natural language processing and information extraction techniques provide a means to identify and formalise the knowledge components required by the knowledge base. Original contributions are made in the development of lexico-syntactic patterns and the use of external domain knowledge resources to tackle a variety of information extraction tasks in the clinical domain, such as recognition of clinical concepts, events, temporal relations, term disambiguation and abbreviation expansion. Methods are developed for adapting existing tools and resources in the biomedical domain to the processing of clinical texts, and approaches to improving the scalability of these tools are proposed and evalu- ated. These tools and techniques are then combined in the creation of a novel approach to identifying processes of care in the clinical narrative. It is demonstrated that resolution of coreferential and anaphoric relations as narratively and temporally ordered chains provides a means to extract linked narrative events and processes of care from clinical notes. Coreference performance in discharge summaries and progress notes is largely dependent on correct identification of protagonist chains (patient, clinician, family relation), pronominal resolution, and string matching that takes account of experiencer, temporal, spatial, and anatomical context; whereas for laboratory reports additional, external domain knowledge is required. The types of external knowledge and their effects on system performance are identified and evaluated. Results are compared against existing systems for solving these tasks and are found to improve on them, or to approach the performance of recently reported, state-of-the- art systems. Software artefacts developed in this research have been made available as open-source components within the General Architecture for Text Engineering framework