NCBO Ontology Recommender 2.0: An Enhanced Approach for Biomedical Ontology Recommendation

Biomedical researchers use ontologies to annotate their data with ontology terms, enabling better data integration and interoperability. However, the number, variety and complexity of current biomedical ontologies make it cumbersome for researchers to determine which ones to reuse for their specific needs. To overcome this problem, in 2010 the National Center for Biomedical Ontology (NCBO) released the Ontology Recommender, which is a service that receives a biomedical text corpus or a list of keywords and suggests ontologies appropriate for referencing the indicated terms. We developed a new version of the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a new recommendation approach that evaluates the relevance of an ontology to biomedical text data according to four criteria: (1) the extent to which the ontology covers the input data; (2) the acceptance of the ontology in the biomedical community; (3) the level of detail of the ontology classes that cover the input data; and (4) the specialization of the ontology to the domain of the input data. Our evaluation shows that the enhanced recommender provides higher quality suggestions than the original approach, providing better coverage of the input data, more detailed information about their concepts, increased specialization for the domain of the input data, and greater acceptance and use in the community. In addition, it provides users with more explanatory information, along with suggestions of not only individual ontologies but also groups of ontologies. It also can be customized to fit the needs of different scenarios. Ontology Recommender 2.0 combines the strengths of its predecessor with a range of adjustments and new features that improve its reliability and usefulness. Ontology Recommender 2.0 recommends over 500 biomedical ontologies from the NCBO BioPortal platform, where it is openly available.Comment: 29 pages, 8 figures, 11 table

Towards Smarter Fluorescence Microscopy: Enabling Adaptive Acquisition Strategies With Optimized Photon Budget

Fluorescence microscopy is an invaluable technique for studying the intricate process of organism development. The acquisition process, however, is associated with the fundamental trade-off between the quality and reliability of the acquired data. On one hand, the goal of capturing the development in its entirety, often times across multiple spatial and temporal scales, requires extended acquisition periods. On the other hand, high doses of light required for such experiments are harmful for living samples and can introduce non-physiological artifacts in the normal course of development. Conventionally, a single set of acquisition parameters is chosen in the beginning of the acquisition and constitutes the experimenter’s best guess of the overall optimal configuration within the aforementioned trade-off. In the paradigm of adaptive microscopy, in turn, one aims at achieving more efficient photon budget distribution by dynamically adjusting the acquisition parameters to the changing properties of the sample. In this thesis, I explore the principles of adaptive microscopy and propose a range of improvements for two real imaging scenarios. Chapter 2 summarizes the design and implementation of an adaptive pipeline for efficient observation of the asymmetrically dividing neurogenic progenitors in Zebrafish retina. In the described approach the fast and expensive acquisition mode is automatically activated only when the mitotic cells are present in the field of view. The method illustrates the benefits of the adaptive acquisition in the common scenario of the individual events of interest being sparsely distributed throughout the duration of the acquisition. Chapter 3 focuses on computational aspects of segmentation-based adaptive schemes for efficient acquisition of the developing Drosophila pupal wing. Fast sample segmentation is shown to provide a valuable output for the accurate evaluation of the sample morphology and dynamics in real time. This knowledge proves instrumental for adjusting the acquisition parameters to the current properties of the sample and reducing the required photon budget with minimal effects to the quality of the acquired data. Chapter 4 addresses the generation of synthetic training data for learning-based methods in bioimage analysis, making them more practical and accessible for smart microscopy pipelines. State-of-the-art deep learning models trained exclusively on the generated synthetic data are shown to yield powerful predictions when applied to the real microscopy images. In the end, in-depth evaluation of the segmentation quality of both real and synthetic data-based models illustrates the important practical aspects of the approach and outlines the directions for further research

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein--protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence ``Protein A causes protein B to bind protein C&#39;&#39; can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP&#39;09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing.&nbsp; Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP&#39;09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP&#39;11 and BioNLP&#39;13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.</p

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein-protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence “Protein A causes protein B to bind protein C” can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP'09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing. Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP'09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP'11 and BioNLP'13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.Siirretty Doriast

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

Ascertaining Pain in Mental Health Records:Combining Empirical and Knowledge-Based Methods for Clinical Modelling of Electronic Health Record Text

In recent years, state-of-the-art clinical Natural Language Processing (NLP), as in other domains, has been dominated by neural networks and other statistical models. In contrast to the unstructured nature of Electronic Health Record (EHR) text, biomedical knowledge is increasingly available in structured and codified forms, underpinned by curated databases, machine-readable clinical guidelines, and logically defined terminologies. This thesis examines the incorporation of external medical knowledge into clinical NLP and tests these methods on a use case of ascertaining physical pain in clinical notes of mental health records.Pain is a common reason for accessing healthcare resources and has been a growing area of research, especially its impact on mental health. Pain also presents a unique NLP problem due to its ambiguous nature and the varying circumstances in which it can be used. For these reasons, pain has been chosen as a use case, making it a good case study for the application of the methods explored in this thesis. Models are built by assimilating both structured medical knowledge and clinical NLP and leveraging the inherent relations that exist within medical ontologies. The data source used in this project is a mental health EHR database called CRIS, which contains de-identified patient records from the South London and Maudsley NHS Foundation Trust, one of the largest mental health providers in Western Europe.A lexicon of pain terms was developed to identify documents within CRIS mentioning painrelated terms. Gold standard annotations were created by conducting manual annotations on these documents. These gold standard annotations were used to build models for a binary classification task, with the objective of classifying sentences from the clinical text as “relevant”, which indicates the sentence contains relevant mentions of pain, i.e., physical pain affecting the patient, or “not relevant”, which indicates the sentence does not contain mentions of physical pain, or the mention does not relate to the patient (ex: someone else in physical pain). Two models incorporating structured medical knowledge were built:1. a transformer-based model, SapBERT, that utilises a knowledge graph of the UMLS ontology, and2. a knowledge graph embedding model that utilises embeddings from SNOMED CT, which was then used to build a random forest classifier. This was achieved by modelling the clinical pain terms and their relations from SNOMED CT into knowledge graph embeddings, thus combining the data-driven view of clinical language, with the logical view of medical knowledge.These models have been compared with NLP models (binary classifiers) that do not incorporate such structured medical knowledge:1. a transformer-based model, BERT_base, and2. a random forest classifier model.Amongst the two transformer-based models, SapBERT performed better at the classification task (F1-score: 0.98), and amongst the random forest models, the one incorporating knowledge graph embeddings performed better (F1-score: 0.94). The SapBERT model was run on sentences from a cohort of patients within CRIS, with the objective of conducting a prevalence study to understand the distribution of pain based on sociodemographic and diagnostic factors.The contribution of this research is both methodological and practical, showing the difference between a conventional NLP approach of binary classification and one that incorporates external knowledge, and further utilising the models obtained from both these approaches ina prevalence study which was designed based on inputs from clinicians and a patient and public involvement group. The results emphasise the significance of going beyond the conventional approach to NLP when addressing complex issues such as pain.<br/

Deep Learning Methods for Automated Classification of Fish Behavior

Masteroppgåve i informatikkINF399MAMN-INFMAMN-PRO