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

On the Use of Parsing for Named Entity Recognition

[Abstract] Parsing is a core natural language processing technique that can be used to obtain the structure underlying sentences in human languages. Named entity recognition (NER) is the task of identifying the entities that appear in a text. NER is a challenging natural language processing task that is essential to extract knowledge from texts in multiple domains, ranging from financial to medical. It is intuitive that the structure of a text can be helpful to determine whether or not a certain portion of it is an entity and if so, to establish its concrete limits. However, parsing has been a relatively little-used technique in NER systems, since most of them have chosen to consider shallow approaches to deal with text. In this work, we study the characteristics of NER, a task that is far from being solved despite its long history; we analyze the latest advances in parsing that make its use advisable in NER settings; we review the different approaches to NER that make use of syntactic information; and we propose a new way of using parsing in NER based on casting parsing itself as a sequence labeling task.Xunta de Galicia; ED431C 2020/11Xunta de Galicia; ED431G 2019/01This work has been funded by MINECO, AEI and FEDER of UE through the ANSWER-ASAP project (TIN2017-85160-C2-1-R); and by Xunta de Galicia through a Competitive Reference Group grant (ED431C 2020/11). CITIC, as Research Center of the Galician University System, is funded by the Consellería de Educación, Universidade e Formación Profesional of the Xunta de Galicia through the European Regional Development Fund (ERDF/FEDER) with 80%, the Galicia ERDF 2014-20 Operational Programme, and the remaining 20% from the Secretaría Xeral de Universidades (Ref. ED431G 2019/01). Carlos Gómez-Rodríguez has also received funding from the European Research Council (ERC), under the European Union’s Horizon 2020 research and innovation programme (FASTPARSE, Grant No. 714150)

Data-efficient methods for information extraction

Strukturierte Wissensrepräsentationssysteme wie Wissensdatenbanken oder Wissensgraphen bieten Einblicke in Entitäten und Beziehungen zwischen diesen Entitäten in der realen Welt. Solche Wissensrepräsentationssysteme können in verschiedenen Anwendungen der natürlichen Sprachverarbeitung eingesetzt werden, z. B. bei der semantischen Suche, der Beantwortung von Fragen und der Textzusammenfassung. Es ist nicht praktikabel und ineffizient, diese Wissensrepräsentationssysteme manuell zu befüllen. In dieser Arbeit entwickeln wir Methoden, um automatisch benannte Entitäten und Beziehungen zwischen den Entitäten aus Klartext zu extrahieren. Unsere Methoden können daher verwendet werden, um entweder die bestehenden unvollständigen Wissensrepräsentationssysteme zu vervollständigen oder ein neues strukturiertes Wissensrepräsentationssystem von Grund auf zu erstellen. Im Gegensatz zu den gängigen überwachten Methoden zur Informationsextraktion konzentrieren sich unsere Methoden auf das Szenario mit wenigen Daten und erfordern keine große Menge an kommentierten Daten. Im ersten Teil der Arbeit haben wir uns auf das Problem der Erkennung von benannten Entitäten konzentriert. Wir haben an der gemeinsamen Aufgabe von Bacteria Biotope 2019 teilgenommen. Die gemeinsame Aufgabe besteht darin, biomedizinische Entitätserwähnungen zu erkennen und zu normalisieren. Unser linguistically informed Named-Entity-Recognition-System besteht aus einem Deep-Learning-basierten Modell, das sowohl verschachtelte als auch flache Entitäten extrahieren kann; unser Modell verwendet mehrere linguistische Merkmale und zusätzliche Trainingsziele, um effizientes Lernen in datenarmen Szenarien zu ermöglichen. Unser System zur Entitätsnormalisierung verwendet String-Match, Fuzzy-Suche und semantische Suche, um die extrahierten benannten Entitäten mit den biomedizinischen Datenbanken zu verknüpfen. Unser System zur Erkennung von benannten Entitäten und zur Entitätsnormalisierung erreichte die niedrigste Slot-Fehlerrate von 0,715 und belegte den ersten Platz in der gemeinsamen Aufgabe. Wir haben auch an zwei gemeinsamen Aufgaben teilgenommen: Adverse Drug Effect Span Detection (Englisch) und Profession Span Detection (Spanisch); beide Aufgaben sammeln Daten von der Social Media Plattform Twitter. Wir haben ein Named-Entity-Recognition-Modell entwickelt, das die Eingabedarstellung des Modells durch das Stapeln heterogener Einbettungen aus verschiedenen Domänen verbessern kann; unsere empirischen Ergebnisse zeigen komplementäres Lernen aus diesen heterogenen Einbettungen. Unser Beitrag belegte den 3. Platz in den beiden gemeinsamen Aufgaben. Im zweiten Teil der Arbeit untersuchten wir Strategien zur Erweiterung synthetischer Daten, um ressourcenarme Informationsextraktion in spezialisierten Domänen zu ermöglichen. Insbesondere haben wir backtranslation an die Aufgabe der Erkennung von benannten Entitäten auf Token-Ebene und der Extraktion von Beziehungen auf Satzebene angepasst. Wir zeigen, dass die Rückübersetzung sprachlich vielfältige und grammatikalisch kohärente synthetische Sätze erzeugen kann und als wettbewerbsfähige Erweiterungsstrategie für die Aufgaben der Erkennung von benannten Entitäten und der Extraktion von Beziehungen dient. Bei den meisten realen Aufgaben zur Extraktion von Beziehungen stehen keine kommentierten Daten zur Verfügung, jedoch ist häufig ein großer unkommentierter Textkorpus vorhanden. Bootstrapping-Methoden zur Beziehungsextraktion können mit diesem großen Korpus arbeiten, da sie nur eine Handvoll Startinstanzen benötigen. Bootstrapping-Methoden neigen jedoch dazu, im Laufe der Zeit Rauschen zu akkumulieren (bekannt als semantische Drift), und dieses Phänomen hat einen drastischen negativen Einfluss auf die endgültige Genauigkeit der Extraktionen. Wir entwickeln zwei Methoden zur Einschränkung des Bootstrapping-Prozesses, um die semantische Drift bei der Extraktion von Beziehungen zu minimieren. Unsere Methoden nutzen die Graphentheorie und vortrainierte Sprachmodelle, um verrauschte Extraktionsmuster explizit zu identifizieren und zu entfernen. Wir berichten über die experimentellen Ergebnisse auf dem TACRED-Datensatz für vier Relationen. Im letzten Teil der Arbeit demonstrieren wir die Anwendung der Domänenanpassung auf die anspruchsvolle Aufgabe der mehrsprachigen Akronymextraktion. Unsere Experimente zeigen, dass die Domänenanpassung die Akronymextraktion in wissenschaftlichen und juristischen Bereichen in sechs Sprachen verbessern kann, darunter auch Sprachen mit geringen Ressourcen wie Persisch und Vietnamesisch.The structured knowledge representation systems such as knowledge base or knowledge graph can provide insights regarding entities and relationship(s) among these entities in the real-world, such knowledge representation systems can be employed in various natural language processing applications such as semantic search, question answering and text summarization. It is infeasible and inefficient to manually populate these knowledge representation systems. In this work, we develop methods to automatically extract named entities and relationships among the entities from plain text and hence our methods can be used to either complete the existing incomplete knowledge representation systems to create a new structured knowledge representation system from scratch. Unlike mainstream supervised methods for information extraction, our methods focus on the low-data scenario and do not require a large amount of annotated data. In the first part of the thesis, we focused on the problem of named entity recognition. We participated in the shared task of Bacteria Biotope 2019, the shared task consists of recognizing and normalizing the biomedical entity mentions. Our linguistically informed named entity recognition system consists of a deep learning based model which can extract both nested and flat entities; our model employed several linguistic features and auxiliary training objectives to enable efficient learning in data-scarce scenarios. Our entity normalization system employed string match, fuzzy search and semantic search to link the extracted named entities to the biomedical databases. Our named entity recognition and entity normalization system achieved the lowest slot error rate of 0.715 and ranked first in the shared task. We also participated in two shared tasks of Adverse Drug Effect Span detection (English) and Profession Span Detection (Spanish); both of these tasks collect data from the social media platform Twitter. We developed a named entity recognition model which can improve the input representation of the model by stacking heterogeneous embeddings from a diverse domain(s); our empirical results demonstrate complementary learning from these heterogeneous embeddings. Our submission ranked 3rd in both of the shared tasks. In the second part of the thesis, we explored synthetic data augmentation strategies to address low-resource information extraction in specialized domains. Specifically, we adapted backtranslation to the token-level task of named entity recognition and sentence-level task of relation extraction. We demonstrate that backtranslation can generate linguistically diverse and grammatically coherent synthetic sentences and serve as a competitive augmentation strategy for the task of named entity recognition and relation extraction. In most of the real-world relation extraction tasks, the annotated data is not available, however, quite often a large unannotated text corpus is available. Bootstrapping methods for relation extraction can operate on this large corpus as they only require a handful of seed instances. However, bootstrapping methods tend to accumulate noise over time (known as semantic drift) and this phenomenon has a drastic negative impact on the final precision of the extractions. We develop two methods to constrain the bootstrapping process to minimise semantic drift for relation extraction; our methods leverage graph theory and pre-trained language models to explicitly identify and remove noisy extraction patterns. We report the experimental results on the TACRED dataset for four relations. In the last part of the thesis, we demonstrate the application of domain adaptation to the challenging task of multi-lingual acronym extraction. Our experiments demonstrate that domain adaptation can improve acronym extraction within scientific and legal domains in 6 languages including low-resource languages such as Persian and Vietnamese

One, no one and one hundred thousand events: Defining and processing events in an inter-disciplinary perspective

We present an overview of event definition and processing spanning 25 years of research in NLP. We first provide linguistic background to the notion of event, and then present past attempts to formalize this concept in annotation standards to foster the development of benchmarks for event extraction systems. This ranges from MUC-3 in 1991 to the Time and Space Track challenge at SemEval 2015. Besides, we shed light on other disciplines in which the notion of event plays a crucial role, with a focus on the historical domain. Our goal is to provide a comprehensive study on event definitions and investigate which potential past efforts in the NLP community may have in a different research domain. We present the results of a questionnaire, where the notion of event for historians is put in relation to the NLP perspective

Knowledge representation and text mining in biomedical, healthcare, and political domains

Knowledge representation and text mining can be employed to discover new knowledge and develop services by using the massive amounts of text gathered by modern information systems. The applied methods should take into account the domain-specific nature of knowledge. This thesis explores knowledge representation and text mining in three application domains. Biomolecular events can be described very precisely and concisely with appropriate representation schemes. Protein–protein interactions are commonly modelled in biological databases as binary relationships, whereas the complex relationships used in text mining are rich in information. The experimental results of this thesis show that complex relationships can be reduced to binary relationships and that it is possible to reconstruct complex relationships from mixtures of linguistically similar relationships. This encourages the extraction of complex relationships from the scientific literature even if binary relationships are required by the application at hand. The experimental results on cross-validation schemes for pair-input data help to understand how existing knowledge regarding dependent instances (such those concerning protein–protein pairs) can be leveraged to improve the generalisation performance estimates of learned models. Healthcare documents and news articles contain knowledge that is more difficult to model than biomolecular events and tend to have larger vocabularies than biomedical scientific articles. This thesis describes an ontology that models patient education documents and their content in order to improve the availability and quality of such documents. The experimental results of this thesis also show that the Recall-Oriented Understudy for Gisting Evaluation measures are a viable option for the automatic evaluation of textual patient record summarisation methods and that the area under the receiver operating characteristic curve can be used in a large-scale sentiment analysis. The sentiment analysis of Reuters news corpora suggests that the Western mainstream media portrays China negatively in politics-related articles but not in general, which provides new evidence to consider in the debate over the image of China in the Western media

Neural information extraction from natural language text

Natural language processing (NLP) deals with building computational techniques that allow computers to automatically analyze and meaningfully represent human language. With an exponential growth of data in this digital era, the advent of NLP-based systems has enabled us to easily access relevant information via a wide range of applications, such as web search engines, voice assistants, etc. To achieve it, a long-standing research for decades has been focusing on techniques at the intersection of NLP and machine learning. In recent years, deep learning techniques have exploited the expressive power of Artificial Neural Networks (ANNs) and achieved state-of-the-art performance in a wide range of NLP tasks. Being one of the vital properties, Deep Neural Networks (DNNs) can automatically extract complex features from the input data and thus, provide an alternative to the manual process of handcrafted feature engineering. Besides ANNs, Probabilistic Graphical Models (PGMs), a coupling of graph theory and probabilistic methods have the ability to describe causal structure between random variables of the system and capture a principled notion of uncertainty. Given the characteristics of DNNs and PGMs, they are advantageously combined to build powerful neural models in order to understand the underlying complexity of data. Traditional machine learning based NLP systems employed shallow computational methods (e.g., SVM or logistic regression) and relied on handcrafting features which is time-consuming, complex and often incomplete. However, deep learning and neural network based methods have recently shown superior results on various NLP tasks, such as machine translation, text classification, namedentity recognition, relation extraction, textual similarity, etc. These neural models can automatically extract an effective feature representation from training data. This dissertation focuses on two NLP tasks: relation extraction and topic modeling. The former aims at identifying semantic relationships between entities or nominals within a sentence or document. Successfully extracting the semantic relationships greatly contributes in building structured knowledge bases, useful in downstream NLP application areas of web search, question-answering, recommendation engines, etc. On other hand, the task of topic modeling aims at understanding the thematic structures underlying in a collection of documents. Topic modeling is a popular text-mining tool to automatically analyze a large collection of documents and understand topical semantics without actually reading them. In doing so, it generates word clusters (i.e., topics) and document representations useful in document understanding and information retrieval, respectively. Essentially, the tasks of relation extraction and topic modeling are built upon the quality of representations learned from text. In this dissertation, we have developed task-specific neural models for learning representations, coupled with relation extraction and topic modeling tasks in the realms of supervised and unsupervised machine learning paradigms, respectively. More specifically, we make the following contributions in developing neural models for NLP tasks: 1. Neural Relation Extraction: Firstly, we have proposed a novel recurrent neural network based architecture for table-filling in order to jointly perform entity and relation extraction within sentences. Then, we have further extended our scope of extracting relationships between entities across sentence boundaries, and presented a novel dependency-based neural network architecture. The two contributions lie in the supervised paradigm of machine learning. Moreover, we have contributed in building a robust relation extractor constrained by the lack of labeled data, where we have proposed a novel weakly-supervised bootstrapping technique. Given the contributions, we have further explored interpretability of the recurrent neural networks to explain their predictions for the relation extraction task. 2. Neural Topic Modeling: Besides the supervised neural architectures, we have also developed unsupervised neural models to learn meaningful document representations within topic modeling frameworks. Firstly, we have proposed a novel dynamic topic model that captures topics over time. Next, we have contributed in building static topic models without considering temporal dependencies, where we have presented neural topic modeling architectures that also exploit external knowledge, i.e., word embeddings to address data sparsity. Moreover, we have developed neural topic models that incorporate knowledge transfers using both the word embeddings and latent topics from many sources. Finally, we have shown improving neural topic modeling by introducing language structures (e.g., word ordering, local syntactic and semantic information, etc.) that deals with bag-of-words issues in traditional topic models. The class of proposed neural NLP models in this section are based on techniques at the intersection of PGMs, deep learning and ANNs. Here, the task of neural relation extraction employs neural networks to learn representations typically at the sentence level, without access to the broader document context. However, topic models have access to statistical information across documents. Therefore, we advantageously combine the two complementary learning paradigms in a neural composite model, consisting of a neural topic and a neural language model that enables us to jointly learn thematic structures in a document collection via the topic model, and word relations within a sentence via the language model. Overall, our research contributions in this dissertation extend NLP-based systems for relation extraction and topic modeling tasks with state-of-the-art performances

Text Mining for Pathway Curation

Biolog:innen untersuchen häufig Pathways, Netzwerke von Interaktionen zwischen Proteinen und Genen mit einer spezifischen Funktion. Neue Erkenntnisse über Pathways werden in der Regel zunächst in Publikationen veröffentlicht und dann in strukturierter Form in Lehrbüchern, Datenbanken oder mathematischen Modellen weitergegeben. Deren Kuratierung kann jedoch aufgrund der hohen Anzahl von Publikationen sehr aufwendig sein. In dieser Arbeit untersuchen wir wie Text Mining Methoden die Kuratierung unterstützen können. Wir stellen PEDL vor, ein Machine-Learning-Modell zur Extraktion von Protein-Protein-Assoziationen (PPAs) aus biomedizinischen Texten. PEDL verwendet Distant Supervision und vortrainierte Sprachmodelle, um eine höhere Genauigkeit als vergleichbare Methoden zu erreichen. Eine Evaluation durch Expert:innen bestätigt die Nützlichkeit von PEDLs für Pathway-Kurator:innen. Außerdem stellen wir PEDL+ vor, ein Kommandozeilen-Tool, mit dem auch Nicht-Expert:innen PPAs effizient extrahieren können. Drei Kurator:innen bewerten 55,6 % bis 79,6 % der von PEDL+ gefundenen PPAs als nützlich für ihre Arbeit. Die große Anzahl von PPAs, die durch Text Mining identifiziert werden, kann für Forscher:innen überwältigend sein. Um hier Abhilfe zu schaffen, stellen wir PathComplete vor, ein Modell, das nützliche Erweiterungen eines Pathways vorschlägt. Es ist die erste Pathway-Extension-Methode, die auf überwachtem maschinellen Lernen basiert. Unsere Experimente zeigen, dass PathComplete wesentlich genauer ist als existierende Methoden. Schließlich schlagen wir eine Methode vor, um Pathways mit komplexen Ereignisstrukturen zu erweitern. Hier übertrifft unsere neue Methode zur konditionalen Graphenmodifikation die derzeit beste Methode um 13-24% Genauigkeit in drei Benchmarks. Insgesamt zeigen unsere Ergebnisse, dass Deep Learning basierte Informationsextraktion eine vielversprechende Grundlage für die Unterstützung von Pathway-Kurator:innen ist.Biological knowledge often involves understanding the interactions between molecules, such as proteins and genes, that form functional networks called pathways. New knowledge about pathways is typically communicated through publications and later condensed into structured formats such as textbooks, pathway databases or mathematical models. However, curating updated pathway models can be labour-intensive due to the growing volume of publications. This thesis investigates text mining methods to support pathway curation. We present PEDL (Protein-Protein-Association Extraction with Deep Language Models), a machine learning model designed to extract protein-protein associations (PPAs) from biomedical text. PEDL uses distant supervision and pre-trained language models to achieve higher accuracy than the state of the art. An expert evaluation confirms its usefulness for pathway curators. We also present PEDL+, a command-line tool that allows non-expert users to efficiently extract PPAs. When applied to pathway curation tasks, 55.6% to 79.6% of PEDL+ extractions were found useful by curators. The large number of PPAs identified by text mining can be overwhelming for researchers. To help, we present PathComplete, a model that suggests potential extensions to a pathway. It is the first method based on supervised machine learning for this task, using transfer learning from pathway databases. Our evaluations show that PathComplete significantly outperforms existing methods. Finally, we generalise pathway extension from PPAs to more realistic complex events. Here, our novel method for conditional graph modification outperforms the current best by 13-24% accuracy on three benchmarks. We also present a new dataset for event-based pathway extension. Overall, our results show that deep learning-based information extraction is a promising basis for supporting pathway curators