eGIFT: Mining Gene Information from the Literature

<p>Abstract</p> <p>Background</p> <p>With the biomedical literature continually expanding, searching PubMed for information about specific genes becomes increasingly difficult. Not only can thousands of results be returned, but gene name ambiguity leads to many irrelevant hits. As a result, it is difficult for life scientists and gene curators to rapidly get an overall picture about a specific gene from documents that mention its names and synonyms.</p> <p>Results</p> <p>In this paper, we present eGIFT (<url>http://biotm.cis.udel.edu/eGIFT</url>), a web-based tool that associates informative terms, called <it>i</it>Terms, and sentences containing them, with genes. To associate <it>i</it>Terms with a gene, eGIFT ranks <it>i</it>Terms about the gene, based on a score which compares the frequency of occurrence of a term in the gene's literature to its frequency of occurrence in documents about genes in general. To retrieve a gene's documents (Medline abstracts), eGIFT considers all gene names, aliases, and synonyms. Since many of the gene names can be ambiguous, eGIFT applies a disambiguation step to remove matches that do not correspond to this gene. Another additional filtering process is applied to retain those abstracts that focus on the gene rather than mention it in passing. eGIFT's information for a gene is pre-computed and users of eGIFT can search for genes by using a name or an EntrezGene identifier. <it>i</it>Terms are grouped into different categories to facilitate a quick inspection. eGIFT also links an <it>i</it>Term to sentences mentioning the term to allow users to see the relation between the <it>i</it>Term and the gene. We evaluated the precision and recall of eGIFT's <it>i</it>Terms for 40 genes; between 88% and 94% of the <it>i</it>Terms were marked as salient by our evaluators, and 94% of the UniProtKB keywords for these genes were also identified by eGIFT as <it>i</it>Terms.</p> <p>Conclusions</p> <p>Our evaluations suggest that <it>i</it>Terms capture highly-relevant aspects of genes. Furthermore, by showing sentences containing these terms, eGIFT can provide a quick description of a specific gene. eGIFT helps not only life scientists survey results of high-throughput experiments, but also annotators to find articles describing gene aspects and functions.</p

Expertise Profiling in Evolving Knowledgecuration Platforms

Expertise modeling has been the subject of extensiveresearch in two main disciplines: Information Retrieval (IR) andSocial Network Analysis (SNA). Both IR and SNA approachesbuild the expertise model through a document-centric approachproviding a macro-perspective on the knowledge emerging fromlarge corpus of static documents. With the emergence of the Webof Data there has been a significant shift from static to evolvingdocuments, through micro-contributions. Thus, the existingmacro-perspective is no longer sufficient to track the evolution ofboth knowledge and expertise. In this paper we present acomprehensive, domain-agnostic model for expertise profiling inthe context of dynamic, living documents and evolving knowledgebases. We showcase its application in the biomedical domain andanalyze its performance using two manually created datasets

Post Processing Wrapper Generated Tables For Labeling Anonymous Datasets

A large number of wrappers generate tables without column names for human consumption because the meaning of the columns are apparent from the context and easy for humans to understand, but in emerging applications, labels are needed for autonomous assignment and schema mapping where machine tries to understand the tables. Autonomous label assignment is critical in volume data processing where ad hoc mediation, extraction and querying is involved. We propose an algorithm Lads for Labeling Anonymous Datasets, which can holistically label/annotate tabular Web document. The algorithm has been tested on anonymous datasets from a number of sites, yielding very promising results. We report here our experimental results on anonymous datasets from a number of sites e.g., music, movie, watch, political, automobile, synthetic obtained through different search engine such as Google, Yahoo and MSN. The comparative probabilities of attributes being candidate labels are presented which seem to be very promising, achieved as high as 98% probability of assigning good label to anonymous attribute. To the best of our knowledge, this is the first of its kind for label assignment based on multiple search engines\u27 recommendation. We have introduced a new paradigm, Web search engine based annotator which can holistically label tabular Web document. We categorize column into three types: disjoint set column (DSC), repeated prefix/suffix column (RPS) and numeric column (NUM). For labeling DSC column, our method rely on hit counts from Web search engine (e.g., Google, Yahoo and MSN). We formulate speculative queries to Web search engine and use the principle of disambiguation by maximal evidence to come up with our solution. Our algorithm Lads is guaranteed to work for the disjoint set column. Experimental results from large number of sites in different domains and subjective evaluation of our approach show that the proposed algorithm Lads works fairly well. In this line we claim that our algorithm Lads is robust. In order to assign label for the Disjoint Set Column, we need a candidate set of labels (e.g., label library) which can be collected on-the-fly from user SQL query variable as well as from Web Form label tag. We classify a set of homogeneous anonymous datasets into meaningful label and at the same time cluster those labels into a label library by learning user expectation and materialization of her expectation from a site. Previous work in this field rely on extraction ontologies, we eliminate the need for domain specific ontologies as we could extract label from the Web form. Our system is novel in the sense that we accommodate label from the user query variable. We hypothesize that our proposed algorithm Lads will do a good job for autonomous label assignment. We bridge the gap between two orthogonal research directions: wrapper generation and ontology generation from Web site (i.e., label extraction). We are NOT aware of any such prior work that address to connect these two orthogonal research for value added services such as online comparison shopping

Development of a text mining approach to disease network discovery

Scientific literature is one of the major sources of knowledge for systems biology, in the form of papers, patents and other types of written reports. Text mining methods aim at automatically extracting relevant information from the literature. The hypothesis of this thesis was that biological systems could be elucidated by the development of text mining solutions that can automatically extract relevant information from documents. The first objective consisted in developing software components to recognize biomedical entities in text, which is the first step to generate a network about a biological system. To this end, a machine learning solution was developed, which can be trained for specific biological entities using an annotated dataset, obtaining high-quality results. Additionally, a rule-based solution was developed, which can be easily adapted to various types of entities. The second objective consisted in developing an automatic approach to link the recognized entities to a reference knowledge base. A solution based on the PageRank algorithm was developed in order to match the entities to the concepts that most contribute to the overall coherence. The third objective consisted in automatically extracting relations between entities, to generate knowledge graphs about biological systems. Due to the lack of annotated datasets available for this task, distant supervision was employed to train a relation classifier on a corpus of documents and a knowledge base. The applicability of this approach was demonstrated in two case studies: microRNAgene relations for cystic fibrosis, obtaining a network of 27 relations using the abstracts of 51 recently published papers; and cell-cytokine relations for tolerogenic cell therapies, obtaining a network of 647 relations from 3264 abstracts. Through a manual evaluation, the information contained in these networks was determined to be relevant. Additionally, a solution combining deep learning techniques with ontology information was developed, to take advantage of the domain knowledge provided by ontologies. This thesis contributed with several solutions that demonstrate the usefulness of text mining methods to systems biology by extracting domain-specific information from the literature. These solutions make it easier to integrate various areas of research, leading to a better understanding of biological systems

Biomedical Information Extraction: Mining Disease Associated Genes from Literature

Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to support hypothesis formulation and decision making. Completion of human genome project and advent of high-throughput technology have produced tremendous amount of data, which results in exponential growing of biomedical knowledge deposited in literature database. The sheer quantity of unexplored information causes information overflow for biomedical researchers, and poses big challenge for informatics researchers to address user's information extraction needs. This thesis focused on mining disease associated genes from PubMed literature database using machine learning and graph theory based information extraction (IE) methods. Mining disease associated genes is not trivial and requires pipelines of information extraction steps and methods. Beginning from named entity recognition (NER), the author introduced semantic concept type into feature space for conditional random fields machine learning and demonstrated the effectiveness of the concept feature for disease NER. The effects of domain specific POS tagging, domain specific dictionaries, and named entity encoding scheme on NER performance were also explored. Experimental results show that by combining knowledge base with concept feature space, it can significantly improve the overall disease NER performance. It has also shown that shallow linguistic features of global and local word sequence context can be used with string kernel based supporting vector machine (SVM) for efficient disease-gene relation extraction. Lastly, the disease-associated gene network was constructed by utilizing concept co-occurrence matrix computed from disease focused document collection, and subjected to systematic topology analysis. The gene network was then merged with a seed-gene expanded network to form heterogeneous disease-gene network. The author identified and prioritized disease-associated genes by graph centrality measurements. This novel approach provides a new mean for disease associated gene extraction from large corpora.Ph.D., Information Studies -- Drexel University, 201

Ontology Enrichment from Free-text Clinical Documents: A Comparison of Alternative Approaches

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships, as well as difficulty in updating the ontology as domain knowledge changes. Methodologies developed in the fields of Natural Language Processing (NLP), Information Extraction (IE), Information Retrieval (IR), and Machine Learning (ML) provide techniques for automating the enrichment of ontology from free-text documents. In this dissertation, I extended these methodologies into biomedical ontology development. First, I reviewed existing methodologies and systems developed in the fields of NLP, IR, and IE, and discussed how existing methods can benefit the development of biomedical ontologies. This previously unconducted review was published in the Journal of Biomedical Informatics. Second, I compared the effectiveness of three methods from two different approaches, the symbolic (the Hearst method) and the statistical (the Church and Lin methods), using clinical free-text documents. Third, I developed a methodological framework for Ontology Learning (OL) evaluation and comparison. This framework permits evaluation of the two types of OL approaches that include three OL methods. The significance of this work is as follows: 1) The results from the comparative study showed the potential of these methods for biomedical ontology enrichment. For the two targeted domains (NCIT and RadLex), the Hearst method revealed an average of 21% and 11% new concept acceptance rates, respectively. The Lin method produced a 74% acceptance rate for NCIT; the Church method, 53%. As a result of this study (published in the Journal of Methods of Information in Medicine), many suggested candidates have been incorporated into the NCIT; 2) The evaluation framework is flexible and general enough that it can analyze the performance of ontology enrichment methods for many domains, thus expediting the process of automation and minimizing the likelihood that key concepts and relationships would be missed as domain knowledge evolves

Information management applied to bioinformatics

Bioinformatics, the discipline concerned with biological information management is essential in the post-genome era, where the complexity of data processing allows for contemporaneous multi level research including that at the genome level, transcriptome level, proteome level, the metabolome level, and the integration of these -omic studies towards gaining an understanding of biology at the systems level. This research is also having a major impact on disease research and drug discovery, particularly through pharmacogenomics studies. In this study innovative resources have been generated via the use of two case studies. One was of the Research & Development Genetics (RDG) department at AstraZeneca, Alderley Park and the other was of the Pharmacogenomics Group at the Sanger Institute in Cambridge UK. In the AstraZeneca case study senior scientists were interviewed using semi-structured interviews to determine information behaviour through the study scientific workflows. Document analysis was used to generate an understanding of the underpinning concepts and fonned one of the sources of context-dependent information on which the interview questions were based. The objectives of the Sanger Institute case study were slightly different as interviews were carried out with eight scientists together with the use of participation observation, to collect data to develop a database standard for one process of their Pharmacogenomics workflow. The results indicated that AstraZeneca would benefit through upgrading their data management solutions in the laboratory and by development of resources for the storage of data from larger scale projects such as whole genome scans. These studies will also generate very large amounts of data and the analysis of these will require more sophisticated statistical methods. At the Sanger Institute a minimum information standard was reported for the manual design of primers and included in a decision making tree developed for Polymerase Chain Reactions (PCRs). This tree also illustrates problems that can be encountered when designing primers along with procedures that can be taken to address such issues.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Enriching information extraction pipelines in clinical decision support systems

Programa Oficial de Doutoramento en Tecnoloxías da Información e as Comunicacións. 5032V01[Resumo] Os estudos sanitarios de múltiples centros son importantes para aumentar a repercusión dos resultados da investigación médica debido ao número de suxeitos que poden participar neles. Para simplificar a execución destes estudos, o proceso de intercambio de datos debería ser sinxelo, por exemplo, mediante o uso de bases de datos interoperables. Con todo, a consecución desta interoperabilidade segue sendo un tema de investigación en curso, sobre todo debido aos problemas de gobernanza e privacidade dos datos. Na primeira fase deste traballo, propoñemos varias metodoloxías para optimizar os procesos de estandarización das bases de datos sanitarias. Este traballo centrouse na estandarización de fontes de datos heteroxéneas nun esquema de datos estándar, concretamente o OMOP CDM, que foi desenvolvido e promovido pola comunidade OHDSI. Validamos a nosa proposta utilizando conxuntos de datos de pacientes con enfermidade de Alzheimer procedentes de distintas institucións. Na seguinte etapa, co obxectivo de enriquecer a información almacenada nas bases de datos de OMOP CDM, investigamos solucións para extraer conceptos clínicos de narrativas non estruturadas, utilizando técnicas de recuperación de información e de procesamento da linguaxe natural. A validación realizouse a través de conxuntos de datos proporcionados en desafíos científicos, concretamente no National NLP Clinical Challenges(n2c2). Na etapa final, propuxémonos simplificar a execución de protocolos de estudos provenientes de múltiples centros, propoñendo solucións novas para perfilar, publicar e facilitar o descubrimento de bases de datos. Algunhas das solucións desenvolvidas están a utilizarse actualmente en tres proxectos europeos destinados a crear redes federadas de bases de datos de saúde en toda Europa.[Resumen] Los estudios sanitarios de múltiples centros son importantes para aumentar la repercusión de los resultados de la investigación médica debido al número de sujetos que pueden participar en ellos. Para simplificar la ejecución de estos estudios, el proceso de intercambio de datos debería ser sencillo, por ejemplo, mediante el uso de bases de datos interoperables. Sin embargo, la consecución de esta interoperabilidad sigue siendo un tema de investigación en curso, sobre todo debido a los problemas de gobernanza y privacidad de los datos. En la primera fase de este trabajo, proponemos varias metodologías para optimizar los procesos de estandarización de las bases de datos sanitarias. Este trabajo se centró en la estandarización de fuentes de datos heterogéneas en un esquema de datos estándar, concretamente el OMOP CDM, que ha sido desarrollado y promovido por la comunidad OHDSI. Validamos nuestra propuesta utilizando conjuntos de datos de pacientes con enfermedad de Alzheimer procedentes de distintas instituciones. En la siguiente etapa, con el objetivo de enriquecer la información almacenada en las bases de datos de OMOP CDM, hemos investigado soluciones para extraer conceptos clínicos de narrativas no estructuradas, utilizando técnicas de recuperación de información y de procesamiento del lenguaje natural. La validación se realizó a través de conjuntos de datos proporcionados en desafíos científicos, concretamente en el National NLP Clinical Challenges (n2c2). En la etapa final, nos propusimos simplificar la ejecución de protocolos de estudios provenientes de múltiples centros, proponiendo soluciones novedosas para perfilar, publicar y facilitar el descubrimiento de bases de datos. Algunas de las soluciones desarrolladas se están utilizando actualmente en tres proyectos europeos destinados a crear redes federadas de bases de datos de salud en toda Europa.[Abstract] Multicentre health studies are important to increase the impact of medical research findings due to the number of subjects that they are able to engage. To simplify the execution of these studies, the data-sharing process should be effortless, for instance, through the use of interoperable databases. However, achieving this interoperability is still an ongoing research topic, namely due to data governance and privacy issues. In the first stage of this work, we propose several methodologies to optimise the harmonisation pipelines of health databases. This work was focused on harmonising heterogeneous data sources into a standard data schema, namely the OMOP CDM which has been developed and promoted by the OHDSI community. We validated our proposal using data sets of Alzheimer’s disease patients from distinct institutions. In the following stage, aiming to enrich the information stored in OMOP CDM databases, we have investigated solutions to extract clinical concepts from unstructured narratives, using information retrieval and natural language processing techniques. The validation was performed through datasets provided in scientific challenges, namely in the National NLP Clinical Challenges (n2c2). In the final stage, we aimed to simplify the protocol execution of multicentre studies, by proposing novel solutions for profiling, publishing and facilitating the discovery of databases. Some of the developed solutions are currently being used in three European projects aiming to create federated networks of health databases across Europe