Doctor of Philosophy

dissertationDomain adaptation of natural language processing systems is challenging because it requires human expertise. While manual e ort is e ective in creating a high quality knowledge base, it is expensive and time consuming. Clinical text adds another layer of complexity to the task due to privacy and con dentiality restrictions that hinder the ability to share training corpora among di erent research groups. Semantic ambiguity is a major barrier for e ective and accurate concept recognition by natural language processing systems. In my research I propose an automated domain adaptation method that utilizes sublanguage semantic schema for all-word word sense disambiguation of clinical narrative. According to the sublanguage theory developed by Zellig Harris, domain-speci c language is characterized by a relatively small set of semantic classes that combine into a small number of sentence types. Previous research relied on manual analysis to create language models that could be used for more e ective natural language processing. Building on previous semantic type disambiguation research, I propose a method of resolving semantic ambiguity utilizing automatically acquired semantic type disambiguation rules applied on clinical text ambiguously mapped to a standard set of concepts. This research aims to provide an automatic method to acquire Sublanguage Semantic Schema (S3) and apply this model to disambiguate terms that map to more than one concept with di erent semantic types. The research is conducted using unmodi ed MetaMap version 2009, a concept recognition system provided by the National Library of Medicine, applied on a large set of clinical text. The project includes creating and comparing models, which are based on unambiguous concept mappings found in seventeen clinical note types. The e ectiveness of the nal application was validated through a manual review of a subset of processed clinical notes using recall, precision and F-score metrics

Doctor of Philosophy

dissertationBiomedical data are a rich source of information and knowledge. Not only are they useful for direct patient care, but they may also offer answers to important population-based questions. Creating an environment where advanced analytics can be performed against biomedical data is nontrivial, however. Biomedical data are currently scattered across multiple systems with heterogeneous data, and integrating these data is a bigger task than humans can realistically do by hand; therefore, automatic biomedical data integration is highly desirable but has never been fully achieved. This dissertation introduces new algorithms that were devised to support automatic and semiautomatic integration of heterogeneous biomedical data. The new algorithms incorporate both data mining and biomedical informatics techniques to create "concept bags" that are used to compute similarity between data elements in the same way that "word bags" are compared in data mining. Concept bags are composed of controlled medical vocabulary concept codes that are extracted from text using named-entity recognition software. To test the new algorithm, three biomedical text similarity use cases were examined: automatically aligning data elements between heterogeneous data sets, determining degrees of similarity between medical terms using a published benchmark, and determining similarity between ICU discharge summaries. The method is highly configurable and 5 different versions were tested. The concept bag method performed particularly well aligning data elements and outperformed the compared algorithms by iv more than 5%. Another configuration that included hierarchical semantics performed particularly well at matching medical terms, meeting or exceeding 30 of 31 other published results using the same benchmark. Results for the third scenario of computing ICU discharge summary similarity were less successful. Correlations between multiple methods were low, including between terminologists. The concept bag algorithms performed consistently and comparatively well and appear to be viable options for multiple scenarios. New applications of the method and ideas for improving the algorithm are being discussed for future work, including several performance enhancements, configuration-based enhancements, and concept vector weighting using the TF-IDF formulas

Systematising and scaling literature curation for genetically determined developmental disorders

The widespread availability of genomic sequencing has transformed the diagnosis of genetically-determined developmental disorders (GDD). However, this type of test often generates a number of genetic variants, which have to be reviewed and related back to the clinical features (phenotype) of the individual being tested. This frequently entails a time-consuming review of the peer-reviewed literature to look for case reports describing variants in the gene(s) of interest. This is particularly true for newly described and/or very rare disorders not covered in phenotype databases. Therefore, there is a need for scalable, automated literature curation to increase the efficiency of this process. This should lead to improvements in the speed in which diagnosis is made, and an increase in the number of individuals who are diagnosed through genomic testing. Phenotypic data in case reports/case series is not usually recorded in a standardised, computationally-tractable format. Plain text descriptions of similar clinical features may be recorded in several different ways. For example, a technical term such as ‘hypertelorism’, may be recorded as its synonym ‘widely spaced eyes’. In addition, case reports are found across a wide range of journals, with different structures and file formats for each publication. The Human Phenotype Ontology (HPO) was developed to store phenotypic data in a computationally-accessible format. Several initiatives have been developed to link diseases to phenotype data, in the form of HPO terms. However, these rely on manual expert curation and therefore are not inherently scalable, and cannot be updated automatically. Methods of extracting phenotype data from text at scale developed to date have relied on abstracts or open access papers. At the time of writing, Europe PubMed Central (EPMC, https://europepmc.org/) contained approximately 39.5 million articles, of which only 3.8 million were open access. Therefore, there is likely a significant volume of phenotypic data which has not been used previously at scale, due to difficulties accessing non-open access manuscripts. In this thesis, I present a method for literature curation which can utilise all relevant published full text through a newly developed package which can download almost all manuscripts licenced by a university or other institution. This is scalable to the full spectrum of GDD. Using manuscripts identified through manual literature review, I use a full text download pipeline and NLP (natural language processing) based methods to generate disease models. These are comprised of HPO terms weighted according to their frequency in the literature. I demonstrate iterative refinement of these models, and use a custom annotated corpus of 50 papers to show the text mining process has high precision and recall. I demonstrate that these models clinically reflect true disease expressivity, as defined by manual comparison with expert literature reviews, for three well-characterised GDD. I compare these disease models to those in the most commonly used genetic disease phenotype databases. I show that the automated disease models have increased depth of phenotyping, i.e. there are more terms than those which are manually-generated. I show that, in comparison to ‘real life’ prospectively gathered phenotypic data, automated disease models outperform existing phenotype databases in predicting diagnosis, as defined by increased area under the curve (by 0.05 and 0.08 using different similarity measures) on ROC curve plots. I present a method for automated PubMed search at scale, to use as input for disease model generation. I annotated a corpus of 6500 abstracts. Using this corpus I show a high precision (up to 0.80) and recall (up to 1.00) for machine learning classifiers used to identify manuscripts relevant to GDD. These use hand-picked domain-specific features, for example utilising specific MeSH terms. This method can be used to scale automated literature curation to the full spectrum of GDD. I also present an analysis of the phenotypic terms used in one year of GDD-relevant papers in a prominent journal. This shows that use of supplemental data and parsing clinical report sections from manuscripts is likely to result in more patient-specific phenotype extraction in future. In summary, I present a method for automated curation of full text from the peer-reviewed literature in the context of GDD. I demonstrate that this method is robust, reflects clinical disease expressivity, outperforms existing manual literature curation, and is scalable. Applying this process to clinical testing in future should improve the efficiency and accuracy of diagnosis

Quality framework for semantic interoperability in health informatics: definition and implementation

Aligned with the increased adoption of Electronic Health Record (EHR) systems, it is recognized that semantic interoperability provides benefits for promoting patient safety and continuity of care. This thesis proposes a framework of quality metrics and recommendations for developing semantic interoperability resources specially focused on clinical information models, which are defined as formal specifications of structure and semantics for representing EHR information for a specific domain or use case. This research started with an exploratory stage that performed a systematic literature review with an international survey about the clinical information modelling best practice and barriers. The results obtained were used to define a set of quality models that were validated through Delphi study methodologies and end user survey, and also compared with related quality standards in those areas that standardization bodies had a related work programme. According to the obtained research results, the defined framework is based in the following models: Development process quality model: evaluates the alignment with the best practice in clinical information modelling and defines metrics for evaluating the tools applied as part of this process. Product quality model: evaluates the semantic interoperability capabilities of clinical information models based on the defined meta-data, data elements and terminology bindings. Quality in use model: evaluates the suitability of adopting semantic interoperability resources by end users in their local projects and organisations. Finally, the quality in use model was implemented within the European Interoperability Asset register developed by the EXPAND project with the aim of applying this quality model in a broader scope to contain any relevant material for guiding the definition, development and implementation of interoperable eHealth systems in our continent. Several European projects already expressed interest in using the register, which will now be sustained by the European Institute for Innovation through Health Data