Doctor of Philosophy

dissertationDisease-specific ontologies, designed to structure and represent the medical knowledge about disease etiology, diagnosis, treatment, and prognosis, are essential for many advanced applications, such as predictive modeling, cohort identification, and clinical decision support. However, manually building disease-specific ontologies is very labor-intensive, especially in the process of knowledge acquisition. On the other hand, medical knowledge has been documented in a variety of biomedical knowledge resources, such as textbook, clinical guidelines, research articles, and clinical data repositories, which offers a great opportunity for an automated knowledge acquisition. In this dissertation, we aim to facilitate the large-scale development of disease-specific ontologies through automated extraction of disease-specific vocabularies from existing biomedical knowledge resources. Three separate studies presented in this dissertation explored both manual and automated vocabulary extraction. The first study addresses the question of whether disease-specific reference vocabularies derived from manual concept acquisition can achieve a near-saturated coverage (or near the greatest possible amount of disease-pertinent concepts) by using a small number of literature sources. Using a general-purpose, manual acquisition approach we developed, this study concludes that a small number of expert-curated biomedical literature resources can prove sufficient for acquiring near-saturated disease-specific vocabularies. The second and third studies introduce automated techniques for extracting disease-specific vocabularies from both MEDLINE citations (title and abstract) and a clinical data repository. In the second study, we developed and assessed a pipeline-based system which extracts disease-specific treatments from PubMed citations. The system has achieved a mean precision of 0.8 for the top 100 extracted treatment concepts. In the third study, we applied classification models to reduce irrelevant disease-concepts associations extracted from MEDLINE citations and electronic medical records. This study suggested the combination of measures of relevance from disparate sources to improve the identification of true-relevant concepts through classification and also demonstrated the generalizability of the studied classification model to new diseases. With the studies, we concluded that existing biomedical knowledge resources are valuable sources for extracting disease-concept associations, from which classification based on statistical measures of relevance could assist a semi-automated generation of disease-specific vocabularies

De-identifying Hospital Discharge Summaries: An End-to-End Framework using Ensemble of Deep Learning Models

Electronic Medical Records (EMRs) contain clinical narrative text that is of great potential value to medical researchers. However, this information is mixed with Personally Identifiable Information (PII) that presents risks to patient and clinician confidentiality. This paper presents an end-to-end de-identification framework to automatically remove PII from hospital discharge summaries. Our corpus included 600 hospital discharge summaries which were extracted from the EMRs of two principal referral hospitals in Sydney, Australia. Our end-to-end de-identification framework consists of three components: 1) Annotation: labelling of PII in the 600 hospital discharge summaries using five pre-defined categories: person, address, date of birth, identification number, phone number; 2) Modelling: training six named entity recognition (NER) deep learning base-models on balanced and imbalanced datasets; and evaluating ensembles that combine all six base-models, the three base-models with the best F1 scores and the three base-models with the best recall scores respectively, using token-level majority voting and stacking methods; and 3) De-identification: removing PII from the hospital discharge summaries. Our results showed that the ensemble model combined using the stacking Support Vector Machine (SVM) method on the three base-models with the best F1 scores achieved excellent results with a F1 score of 99.16% on the test set of our corpus. We also evaluated the robustness of our modelling component on the 2014 i2b2 de-identification dataset. Our ensemble model, which uses the token-level majority voting method on all six base-models, achieved the highest F1 score of 96.24% at strict entity matching and the highest F1 score of 98.64% at binary token-level matching compared to two state-of-the-art methods. The framework provides a robust solution to de-identifying clinical narrative text safely

BioVerbNet: a large semantic-syntactic classification of verbs in biomedicine.

BackgroundRecent advances in representation learning have enabled large strides in natural language understanding; However, verbal reasoning remains a challenge for state-of-the-art systems. External sources of structured, expert-curated verb-related knowledge have been shown to boost model performance in different Natural Language Processing (NLP) tasks where accurate handling of verb meaning and behaviour is critical. The costliness and time required for manual lexicon construction has been a major obstacle to porting the benefits of such resources to NLP in specialised domains, such as biomedicine. To address this issue, we combine a neural classification method with expert annotation to create BioVerbNet. This new resource comprises 693 verbs assigned to 22 top-level and 117 fine-grained semantic-syntactic verb classes. We make this resource available complete with semantic roles and VerbNet-style syntactic frames.ResultsWe demonstrate the utility of the new resource in boosting model performance in document- and sentence-level classification in biomedicine. We apply an established retrofitting method to harness the verb class membership knowledge from BioVerbNet and transform a pretrained word embedding space by pulling together verbs belonging to the same semantic-syntactic class. The BioVerbNet knowledge-aware embeddings surpass the non-specialised baseline by a significant margin on both tasks.ConclusionThis work introduces the first large, annotated semantic-syntactic classification of biomedical verbs, providing a detailed account of the annotation process, the key differences in verb behaviour between the general and biomedical domain, and the design choices made to accurately capture the meaning and properties of verbs used in biomedical texts. The demonstrated benefits of leveraging BioVerbNet in text classification suggest the resource could help systems better tackle challenging NLP tasks in biomedicine

Structuring the Unstructured: Unlocking pharmacokinetic data from journals with Natural Language Processing

The development of a new drug is an increasingly expensive and inefficient process. Many drug candidates are discarded due to pharmacokinetic (PK) complications detected at clinical phases. It is critical to accurately estimate the PK parameters of new drugs before being tested in humans since they will determine their efficacy and safety outcomes. Preclinical predictions of PK parameters are largely based on prior knowledge from other compounds, but much of this potentially valuable data is currently locked in the format of scientific papers. With an ever-increasing amount of scientific literature, automated systems are essential to exploit this resource efficiently. Developing text mining systems that can structure PK literature is critical to improving the drug development pipeline. This thesis studied the development and application of text mining resources to accelerate the curation of PK databases. Specifically, the development of novel corpora and suitable natural language processing architectures in the PK domain were addressed. The work presented focused on machine learning approaches that can model the high diversity of PK studies, parameter mentions, numerical measurements, units, and contextual information reported across the literature. Additionally, architectures and training approaches that could efficiently deal with the scarcity of annotated examples were explored. The chapters of this thesis tackle the development of suitable models and corpora to (1) retrieve PK documents, (2) recognise PK parameter mentions, (3) link PK entities to a knowledge base and (4) extract relations between parameter mentions, estimated measurements, units and other contextual information. Finally, the last chapter of this thesis studied the feasibility of the whole extraction pipeline to accelerate tasks in drug development research. The results from this thesis exhibited the potential of text mining approaches to automatically generate PK databases that can aid researchers in the field and ultimately accelerate the drug development pipeline. Additionally, the thesis presented contributions to biomedical natural language processing by developing suitable architectures and corpora for multiple tasks, tackling novel entities and relations within the PK domain

Machine understanding surgical actions from intervention procedure textbooks

The automatic extraction of procedural surgical knowledge from surgery manuals, academic papers or other high-quality textual resources, is of the utmost importance to develop knowledge-based clinical decision support systems, to automatically execute some procedure’s step or to summarize the procedural information, spread throughout the texts, in a structured form usable as a study resource by medical students. In this work, we propose a first benchmark on extracting detailed surgical actions from available intervention procedure textbooks and papers. We frame the problem as a Semantic Role Labeling task. Exploiting a manually annotated dataset, we apply different Transformer-based information extraction methods. Starting from RoBERTa and BioMedRoBERTa pre-trained language models, we first investigate a zero-shot scenario and compare the obtained results with a full fine-tuning setting. We then introduce a new ad-hoc surgical language model, named SurgicBERTa, pre-trained on a large collection of surgical materials, and we compare it with the previous ones. In the assessment, we explore different dataset splits (one in-domain and two out-of-domain) and we investigate also the effectiveness of the approach in a few-shot learning scenario. Performance is evaluated on three correlated sub-tasks: predicate disambiguation, semantic argument disambiguation and predicate-argument disambiguation. Results show that the fine-tuning of a pre-trained domain-specific language model achieves the highest performance on all splits and on all sub-tasks. All models are publicly released