Scientists’ sense making when hypothesizing about disease mechanisms from expression data and their needs for visualization support

Abstract A common class of biomedical analysis is to explore expression data from high throughput experiments for the purpose of uncovering functional relationships that can lead to a hypothesis about mechanisms of a disease. We call this analysis expression driven, -omics hypothesizing. In it, scientists use interactive data visualizations and read deeply in the research literature. Little is known, however, about the actual flow of reasoning and behaviors (sense making) that scientists enact in this analysis, end-to-end. Understanding this flow is important because if bioinformatics tools are to be truly useful they must support it. Sense making models of visual analytics in other domains have been developed and used to inform the design of useful and usable tools. We believe they would be helpful in bioinformatics. To characterize the sense making involved in expression-driven, -omics hypothesizing, we conducted an in-depth observational study of one scientist as she engaged in this analysis over six months. From findings, we abstracted a preliminary sense making model. Here we describe its stages and suggest guidelines for developing visualization tools that we derived from this case. A single case cannot be generalized. But we offer our findings, sense making model and case-based tool guidelines as a first step toward increasing interest and further research in the bioinformatics field on scientists’ analytical workflows and their implications for tool design.http://deepblue.lib.umich.edu/bitstream/2027.42/109495/1/12859_2012_Article_6377.pd

Bioinformatics tools in predictive ecology: Applications to fisheries

This article is made available throught the Brunel Open Access Publishing Fund - Copygith @ 2012 Tucker et al.There has been a huge effort in the advancement of analytical techniques for molecular biological data over the past decade. This has led to many novel algorithms that are specialized to deal with data associated with biological phenomena, such as gene expression and protein interactions. In contrast, ecological data analysis has remained focused to some degree on off-the-shelf statistical techniques though this is starting to change with the adoption of state-of-the-art methods, where few assumptions can be made about the data and a more explorative approach is required, for example, through the use of Bayesian networks. In this paper, some novel bioinformatics tools for microarray data are discussed along with their ‘crossover potential’ with an application to fisheries data. In particular, a focus is made on the development of models that identify functionally equivalent species in different fish communities with the aim of predicting functional collapse

Doctor of Philosophy

dissertationElectronic Health Records (EHRs) provide a wealth of information for secondary uses. Methods are developed to improve usefulness of free text query and text processing and demonstrate advantages to using these methods for clinical research, specifically cohort identification and enhancement. Cohort identification is a critical early step in clinical research. Problems may arise when too few patients are identified, or the cohort consists of a nonrepresentative sample. Methods of improving query formation through query expansion are described. Inclusion of free text search in addition to structured data search is investigated to determine the incremental improvement of adding unstructured text search over structured data search alone. Query expansion using topic- and synonym-based expansion improved information retrieval performance. An ensemble method was not successful. The addition of free text search compared to structured data search alone demonstrated increased cohort size in all cases, with dramatic increases in some. Representation of patients in subpopulations that may have been underrepresented otherwise is also shown. We demonstrate clinical impact by showing that a serious clinical condition, scleroderma renal crisis, can be predicted by adding free text search. A novel information extraction algorithm is developed and evaluated (Regular Expression Discovery for Extraction, or REDEx) for cohort enrichment. The REDEx algorithm is demonstrated to accurately extract information from free text clinical iv narratives. Temporal expressions as well as bodyweight-related measures are extracted. Additional patients and additional measurement occurrences are identified using these extracted values that were not identifiable through structured data alone. The REDEx algorithm transfers the burden of machine learning training from annotators to domain experts. We developed automated query expansion methods that greatly improve performance of keyword-based information retrieval. We also developed NLP methods for unstructured data and demonstrate that cohort size can be greatly increased, a more complete population can be identified, and important clinical conditions can be detected that are often missed otherwise. We found a much more complete representation of patients can be obtained. We also developed a novel machine learning algorithm for information extraction, REDEx, that efficiently extracts clinical values from unstructured clinical text, adding additional information and observations over what is available in structured text alone

The use of computer-interpretable clinical guidelines to manage care complexities of patients with multimorbid conditions : a review

Clinical practice guidelines (CPGs) document evidence-based information and recommendations on treatment and management of conditions. CPGs usually focus on management of a single condition; however, in many cases a patient will be at the centre of multiple health conditions (multimorbidity). Multiple CPGs need to be followed in parallel, each managing a separate condition, which often results in instructions that may interact with each other, such as conflicts in medication. Furthermore, the impetus to deliver customised care based on patient-specific information, results in the need to be able to offer guidelines in an integrated manner, identifying and managing their interactions. In recent years, CPGs have been formatted as computer-interpretable guidelines (CIGs). This enables developing CIG-driven clinical decision support systems (CDSSs), which allow the development of IT applications that contribute to the systematic and reliable management of multiple guidelines. This study focuses on understanding the use of CIG-based CDSSs, in order to manage care complexities of patients with multimorbidity. The literature between 2011 and 2017 is reviewed, which covers: (a) the challenges and barriers in the care of multimorbid patients, (b) the role of CIGs in CDSS augmented delivery of care, and (c) the approaches to alleviating care complexities of multimorbid patients. Generating integrated care plans, detecting and resolving adverse interactions between treatments and medications, dealing with temporal constraints in care steps, supporting patient-caregiver shared decision making and maintaining the continuity of care are some of the approaches that are enabled using a CIG-based CDSS

Affective neuroscience, emotional regulation, and international relations

International relations (IR) has witnessed an emerging interest in neuroscience, particularly for its relevance to a now widespread scholarship on emotions. Contributing to this scholarship, this article draws on the subfields of affective neuroscience and neuropsychology, which remain largely unexplored in IR. Firstly, the article draws on affective neuroscience in illuminating affect's defining role in consciousness and omnipresence in social behavior, challenging the continuing elision of emotions in mainstream approaches. Secondly, it applies theories of depth neuropsychology, which suggest a neural predisposition originating in the brain's higher cortical regions to attenuate emotional arousal and limit affective consciousness. This predisposition works to preserve individuals' self-coherence, countering implicit assumptions about rationality and motivation within IR theory. Thirdly, it outlines three key implications for IR theory. It argues that affective neuroscience and neuropsychology offer a route towards deep theorizing of ontologies and motivations. It also leads to a reassessment of the social regulation of emotions, particularly as observed in institutions, including the state. It also suggests a productive engagement with constructivist and poststructuralist approaches by addressing the agency of the body in social relations. The article concludes by sketching the potential for a therapeutically-attuned approach to IR

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

Temporal disambiguation of relative temporal expressions in clinical texts using temporally fine-tuned contextual word embeddings.

Temporal reasoning is the ability to extract and assimilate temporal information to reconstruct a series of events such that they can be reasoned over to answer questions involving time. Temporal reasoning in the clinical domain is challenging due to specialized medical terms and nomenclature, shorthand notation, fragmented text, a variety of writing styles used by different medical units, redundancy of information that has to be reconciled, and an increased number of temporal references as compared to general domain texts. Work in the area of clinical temporal reasoning has progressed, but the current state-of-the-art still has a ways to go before practical application in the clinical setting will be possible. Much of the current work in this field is focused on direct and explicit temporal expressions and identifying temporal relations. However, there is little work focused on relative temporal expressions, which can be difficult to normalize, but are vital to ordering events on a timeline. This work introduces a new temporal expression recognition and normalization tool, Chrono, that normalizes temporal expressions into both SCATE and TimeML schemes. Chrono advances clinical timeline extraction as it is capable of identifying more vague and relative temporal expressions than the current state-of-the-art and utilizes contextualized word embeddings from fine-tuned BERT models to disambiguate temporal types, which achieves state-of-the-art performance on relative temporal expressions. In addition, this work shows that fine-tuning BERT models on temporal tasks modifies the contextualized embeddings so that they achieve improved performance in classical SVM and CNN classifiers. Finally, this works provides a new tool for linking temporal expressions to events or other entities by introducing a novel method to identify which tokens an entire temporal expression is paying the most attention to by summarizing the attention weight matrices output by BERT models