Soft tagging of overlapping high confidence gene mention variants for cross-species full-text gene normalization

Abstract Background Previously, gene normalization (GN) systems are mostly focused on disambiguation using contextual information. An effective gene mention tagger is deemed unnecessary because the subsequent steps will filter out false positives and high recall is sufficient. However, unlike similar tasks in the past BioCreative challenges, the BioCreative III GN task is particularly challenging because it is not species-specific. Required to process full-length articles, an ineffective gene mention tagger may produce a huge number of ambiguous false positives that overwhelm subsequent filtering steps while still missing many true positives. Results We present our GN system participated in the BioCreative III GN task. Our system applies a typical 2-stage approach to GN but features a soft tagging gene mention tagger that generates a set of overlapping gene mention variants with a nearly perfect recall. The overlapping gene mention variants increase the chance of precise match in the dictionary and alleviate the need of disambiguation. Our GN system achieved a precision of 0.9 (F-score 0.63) on the BioCreative III GN test corpus with the silver annotation of 507 articles. Its TAP-k scores are competitive to the best results among all participants. Conclusions We show that despite the lack of clever disambiguation in our gene normalization system, effective soft tagging of gene mention variants can indeed contribute to performance in cross-species and full-text gene normalization.</p

The gene normalization task in BioCreative III

BACKGROUND: We report the Gene Normalization (GN) challenge in BioCreative III where participating teams were asked to return a ranked list of identifiers of the genes detected in full-text articles. For training, 32 fully and 500 partially annotated articles were prepared. A total of 507 articles were selected as the test set. Due to the high annotation cost, it was not feasible to obtain gold-standard human annotations for all test articles. Instead, we developed an Expectation Maximization (EM) algorithm approach for choosing a small number of test articles for manual annotation that were most capable of differentiating team performance. Moreover, the same algorithm was subsequently used for inferring ground truth based solely on team submissions. We report team performance on both gold standard and inferred ground truth using a newly proposed metric called Threshold Average Precision (TAP-k). RESULTS: We received a total of 37 runs from 14 different teams for the task. When evaluated using the gold-standard annotations of the 50 articles, the highest TAP-k scores were 0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20), respectively. Higher TAP-k scores of 0.4916 (k=5, 10, 20) were observed when evaluated using the inferred ground truth over the full test set. When combining team results using machine learning, the best composite system achieved TAP-k scores of 0.3707 (k=5), 0.4311 (k=10), and 0.4477 (k=20) on the gold standard, representing improvements of 12.4%, 21.8%, and 26.6% over the best team results, respectively. CONCLUSIONS: By using full text and being species non-specific, the GN task in BioCreative III has moved closer to a real literature curation task than similar tasks in the past and presents additional challenges for the text mining community, as revealed in the overall team results. By evaluating teams using the gold standard, we show that the EM algorithm allows team submissions to be differentiated while keeping the manual annotation effort feasible. Using the inferred ground truth we show measures of comparative performance between teams. Finally, by comparing team rankings on gold standard vs. inferred ground truth, we further demonstrate that the inferred ground truth is as effective as the gold standard for detecting good team performance

Utilização de dados estruturados na resposta a perguntas relacionadas com saúde

The current standard way of searching for information is through the usage of some kind of search engine. Even though there has been progress, it still is mainly based on the retrieval of a list of documents in which the words you searched for appear. Since the users goal is to find an answer to a question, having to look through multiple documents hoping that one of them have the information they are looking for is not very efficient. The aim of this thesis is to improve that process of searching for information, in this case of medical knowledge in two different ways, the first one is replacing the usual keywords used in search engines for something that is more natural to humans, a question in its natural form. The second one is to make use of the additional information that is present in a question format to provide the user an answer for that same question instead of a list of documents where those keywords are present. Since social media are the place where people replace the queries used on a search engine for questions that are usually answered by humans, it seems the natural place to look for the questions that we aim to provide with automatic answers. The first step to provide an answer to those questions will be to classify them in order to find what kind of information should be present in its answer. The second step is to identify the keywords that would be present if this was to be searched through the currently standard way. Having the keywords identified and knowing what kind of information the question aims to retrieve, it is now possible to map it into a query format and retrieve the information needed to provide an answer.Atualmente a forma mais comum de procurar informação é através da utilização de um motor de busca. Apesar de haver progresso os seus resultados continuam a ser maioritariamente baseados na devolução de uma lista de documentos onde estão presentes as palavras utilizadas na pesquisa, tendo o utilizador posteriormente que percorrer um conjunto dos documentos apresentados na esperança de obter a informação que procura. Para além de ser uma forma menos natural de procurar informação também é menos eficiente. O objetivo para esta tese é melhorar esse processo de procura de informação, sendo neste caso o foco a área da saúde. Estas melhorias aconteceriam de duas formas diferentes, sendo a primeira a substituição da query normalmente utilizada em motores de busca, por algo que nos é mais natural - uma pergunta. E a segunda seria aproveitar a informação adicional a que temos acesso apenas no formato de pergunta, para fornecer os dados necessários à sua resposta em vez de uma lista de documentos onde um conjunto de palavras-chave estão presentes. Sendo as redes sociais o local onde a busca por informação acontece através da utilização de perguntas, em substituição do que seria normal num motor de busca, pelo facto de a resposta nestas plataformas ser normalmente respondida por humanos e não máquinas. Parece assim ser o local natural para a recolha de perguntas para as quais temos o objetivo de fornecer uma ferramenta para a obtenção automática de uma resposta. O primeiro passo para ser possível fornecer esta resposta será a classificação das perguntas em diferentes tipos, tornando assim possível identificar qual a informação que se pretende obter. O segundo passo será identificar e categorizar as palavras de contexto biomédico presentes no texto fornecido, que seriam aquelas utilizadas caso a procura estivesse a ser feita utilizando as ferramentas convencionais. Tendo as palavras-chave sido identificadas e sabendo qual o tipo de informação que deverá estar presente na sua resposta. É agora possível mapear esta informação para um formato conhecido pelos computadores (query) e assim obter a informação pretendida.Mestrado em Engenharia Informátic

Optimizing text mining methods for improving biomedical natural language processing

The overwhelming amount and the increasing rate of publication in the biomedical domain make it difficult for life sciences researchers to acquire and maintain all information that is necessary for their research. Pubmed (the primary citation database for the biomedical literature) currently contains over 21 million article abstracts and more than one million of them were published in 2020 alone. Even though existing article databases provide capable keyword search services, typical everyday-life queries usually return thousands of relevant articles. For instance, a cancer research scientist may need to acquire a complete list of genes that interact with BRCA1 (breast cancer 1) gene. The PubMed keyword search for BRCA1 returns over 16,500 article abstracts, making manual inspection of the retrieved documents impractical. Missing even one of the interacting gene partners in this scenario may jeopardize successful development of a potential new drug or vaccine. Although manually curated databases of biomolecular interactions exist, they are usually not up-to-date and they require notable human effort to maintain. To summarize, new discoveries are constantly being shared within the community via scientific publishing, but unfortunately the probability of missing vital information for research in life sciences is increasing. In response to this problem, the biomedical natural language processing (BioNLP) community of researchers has emerged and strives to assist life sciences researchers by building modern language processing and text mining tools that can be applied at large-scale and scan the whole publicly available literature and extract, classify, and aggregate the information found within, thus keeping life sciences researchers always up-to-date with the recent relevant discoveries and facilitating their research in numerous fields such as molecular biology, biomedical engineering, bioinformatics, genetics engineering and biochemistry. My research has almost exclusively focused on biomedical relation and event extraction tasks. These foundational information extraction tasks deal with automatic detection of biological processes, interactions and relations described in the biomedical literature. Precisely speaking, biomedical relation and event extraction systems can scan through a vast amount of biomedical texts and automatically detect and extract the semantic relations of biomedical named entities (e.g. genes, proteins, chemical compounds, and diseases). The structured outputs of such systems (i.e., the extracted relations or events) can be stored as relational databases or molecular interaction networks which can easily be queried, filtered, analyzed, visualized and integrated with other structured data sources. Extracting biomolecular interactions has always been the primary interest of BioNLP researcher because having knowledge about such interactions is crucially important in various research areas including precision medicine, drug discovery, drug repurposing, hypothesis generation, construction and curation of signaling pathways, and protein function and structure prediction. State-of-the-art relation and event extraction methods are based on supervised machine learning, requiring manually annotated data for training. Manual annotation for the biomedical domain requires domain expertise and it is time-consuming. Hence, having minimal training data for building information extraction systems is a common case in the biomedical domain. This demands development of methods that can make the most out of available training data and this thesis gathers all my research efforts and contributions in that direction. It is worth mentioning that biomedical natural language processing has undergone a revolution since I started my research in this field almost ten years ago. As a member of the BioNLP community, I have witnessed the emergence, improvement– and in some cases, the disappearance–of many methods, each pushing the performance of the best previous method one step further. I can broadly divide the last ten years into three periods. Once I started my research, feature-based methods that relied on heavy feature engineering were dominant and popular. Then, significant advancements in the hardware technology, as well as several breakthroughs in the algorithms and methods enabled machine learning practitioners to seriously utilize artificial neural networks for real-world applications. In this period, convolutional, recurrent, and attention-based neural network models became dominant and superior. Finally, the introduction of transformer-based language representation models such as BERT and GPT impacted the field and resulted in unprecedented performance improvements on many data sets. When reading this thesis, I demand the reader to take into account the course of history and judge the methods and results based on what could have been done in that particular period of the history

The fully automated construction of metabolic pathways using text mining and knowledge-based constraints

Understanding metabolic pathways is one of the most important fields in bioscience in the post-genomic era, but curating metabolic pathways requires considerable man-power. As such there is a lack of reliable experimentally verified metabolic pathways in databases and databases are forced to predict all but the most immediately useful pathways by inheriting annotations from other organisms where the pathway has been curated. Due to the lack of curated data there has been no large scale study to assess the accuracy of current methods for inheriting metabolic pathway annotations. In this thesis I describe the development of the Literature Metabolic Pathway Extraction Tool (LiMPET), a text-mining tool designed for the automated extraction of metabolic pathways from article abstracts and full-text open-access articles. I propose the use of LiMPET by metabolic pathway curators to increase the rate of curation and by individual researchers interested in a particular pathway. The mining of metabolic pathways from the literature has been largely neglected by the textmining community. The work described in this thesis shows the tractability of the problem, however, and it is my hope that it attracts more research into the area

Semi-automated Ontology Generation for Biocuration and Semantic Search

Background: In the life sciences, the amount of literature and experimental data grows at a tremendous rate. In order to effectively access and integrate these data, biomedical ontologies – controlled, hierarchical vocabularies – are being developed. Creating and maintaining such ontologies is a difficult, labour-intensive, manual process. Many computational methods which can support ontology construction have been proposed in the past. However, good, validated systems are largely missing. Motivation: The biocuration community plays a central role in the development of ontologies. Any method that can support their efforts has the potential to have a huge impact in the life sciences. Recently, a number of semantic search engines were created that make use of biomedical ontologies for document retrieval. To transfer the technology to other knowledge domains, suitable ontologies need to be created. One area where ontologies may prove particularly useful is the search for alternative methods to animal testing, an area where comprehensive search is of special interest to determine the availability or unavailability of alternative methods. Results: The Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG) developed in this thesis is a system which supports the creation and extension of ontologies by semi-automatically generating terms, definitions, and parent-child relations from text in PubMed, the web, and PDF repositories. The system is seamlessly integrated into OBO-Edit and Protégé, two widely used ontology editors in the life sciences. DOG4DAG generates terms by identifying statistically significant noun-phrases in text. For definitions and parent-child relations it employs pattern-based web searches. Each generation step has been systematically evaluated using manually validated benchmarks. The term generation leads to high quality terms also found in manually created ontologies. Definitions can be retrieved for up to 78% of terms, child ancestor relations for up to 54%. No other validated system exists that achieves comparable results. To improve the search for information on alternative methods to animal testing an ontology has been developed that contains 17,151 terms of which 10% were newly created and 90% were re-used from existing resources. This ontology is the core of Go3R, the first semantic search engine in this field. When a user performs a search query with Go3R, the search engine expands this request using the structure and terminology of the ontology. The machine classification employed in Go3R is capable of distinguishing documents related to alternative methods from those which are not with an F-measure of 90% on a manual benchmark. Approximately 200,000 of the 19 million documents listed in PubMed were identified as relevant, either because a specific term was contained or due to the automatic classification. The Go3R search engine is available on-line under www.Go3R.org

Semi-automated Ontology Generation for Biocuration and Semantic Search

Background: In the life sciences, the amount of literature and experimental data grows at a tremendous rate. In order to effectively access and integrate these data, biomedical ontologies – controlled, hierarchical vocabularies – are being developed. Creating and maintaining such ontologies is a difficult, labour-intensive, manual process. Many computational methods which can support ontology construction have been proposed in the past. However, good, validated systems are largely missing. Motivation: The biocuration community plays a central role in the development of ontologies. Any method that can support their efforts has the potential to have a huge impact in the life sciences. Recently, a number of semantic search engines were created that make use of biomedical ontologies for document retrieval. To transfer the technology to other knowledge domains, suitable ontologies need to be created. One area where ontologies may prove particularly useful is the search for alternative methods to animal testing, an area where comprehensive search is of special interest to determine the availability or unavailability of alternative methods. Results: The Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG) developed in this thesis is a system which supports the creation and extension of ontologies by semi-automatically generating terms, definitions, and parent-child relations from text in PubMed, the web, and PDF repositories. The system is seamlessly integrated into OBO-Edit and Protégé, two widely used ontology editors in the life sciences. DOG4DAG generates terms by identifying statistically significant noun-phrases in text. For definitions and parent-child relations it employs pattern-based web searches. Each generation step has been systematically evaluated using manually validated benchmarks. The term generation leads to high quality terms also found in manually created ontologies. Definitions can be retrieved for up to 78% of terms, child ancestor relations for up to 54%. No other validated system exists that achieves comparable results. To improve the search for information on alternative methods to animal testing an ontology has been developed that contains 17,151 terms of which 10% were newly created and 90% were re-used from existing resources. This ontology is the core of Go3R, the first semantic search engine in this field. When a user performs a search query with Go3R, the search engine expands this request using the structure and terminology of the ontology. The machine classification employed in Go3R is capable of distinguishing documents related to alternative methods from those which are not with an F-measure of 90% on a manual benchmark. Approximately 200,000 of the 19 million documents listed in PubMed were identified as relevant, either because a specific term was contained or due to the automatic classification. The Go3R search engine is available on-line under www.Go3R.org

Discovering lesser known molecular players and mechanistic patterns in Alzheimer's disease using an integrative disease modelling approach

Convergence of exponentially advancing technologies is driving medical research with life changing discoveries. On the contrary, repeated failures of high-profile drugs to battle Alzheimer's disease (AD) has made it one of the least successful therapeutic area. This failure pattern has provoked researchers to grapple with their beliefs about Alzheimer's aetiology. Thus, growing realisation that Amyloid-β and tau are not 'the' but rather 'one of the' factors necessitates the reassessment of pre-existing data to add new perspectives. To enable a holistic view of the disease, integrative modelling approaches are emerging as a powerful technique. Combining data at different scales and modes could considerably increase the predictive power of the integrative model by filling biological knowledge gaps. However, the reliability of the derived hypotheses largely depends on the completeness, quality, consistency, and context-specificity of the data. Thus, there is a need for agile methods and approaches that efficiently interrogate and utilise existing public data. This thesis presents the development of novel approaches and methods that address intrinsic issues of data integration and analysis in AD research. It aims to prioritise lesser-known AD candidates using highly curated and precise knowledge derived from integrated data. Here much of the emphasis is put on quality, reliability, and context-specificity. This thesis work showcases the benefit of integrating well-curated and disease-specific heterogeneous data in a semantic web-based framework for mining actionable knowledge. Furthermore, it introduces to the challenges encountered while harvesting information from literature and transcriptomic resources. State-of-the-art text-mining methodology is developed to extract miRNAs and its regulatory role in diseases and genes from the biomedical literature. To enable meta-analysis of biologically related transcriptomic data, a highly-curated metadata database has been developed, which explicates annotations specific to human and animal models. Finally, to corroborate common mechanistic patterns — embedded with novel candidates — across large-scale AD transcriptomic data, a new approach to generate gene regulatory networks has been developed. The work presented here has demonstrated its capability in identifying testable mechanistic hypotheses containing previously unknown or emerging knowledge from public data in two major publicly funded projects for Alzheimer's, Parkinson's and Epilepsy diseases

The fully automated construction of metabolic pathways using text mining and knowledge-based constraints

Understanding metabolic pathways is one of the most important fields in bioscience in the post-genomic era, but curating metabolic pathways requires considerable man-power. As such there is a lack of reliable experimentally verified metabolic pathways in databases and databases are forced to predict all but the most immediately useful pathways by inheriting annotations from other organisms where the pathway has been curated. Due to the lack of curated data there has been no large scale study to assess the accuracy of current methods for inheriting metabolic pathway annotations. In this thesis I describe the development of the Literature Metabolic Pathway Extraction Tool (LiMPET), a text-mining tool designed for the automated extraction of metabolic pathways from article abstracts and full-text open-access articles. I propose the use of LiMPET by metabolic pathway curators to increase the rate of curation and by individual researchers interested in a particular pathway. The mining of metabolic pathways from the literature has been largely neglected by the textmining community. The work described in this thesis shows the tractability of the problem, however, and it is my hope that it attracts more research into the area