Extracting Biomolecular Interactions Using Semantic Parsing of Biomedical Text

We advance the state of the art in biomolecular interaction extraction with three contributions: (i) We show that deep, Abstract Meaning Representations (AMR) significantly improve the accuracy of a biomolecular interaction extraction system when compared to a baseline that relies solely on surface- and syntax-based features; (ii) In contrast with previous approaches that infer relations on a sentence-by-sentence basis, we expand our framework to enable consistent predictions over sets of sentences (documents); (iii) We further modify and expand a graph kernel learning framework to enable concurrent exploitation of automatically induced AMR (semantic) and dependency structure (syntactic) representations. Our experiments show that our approach yields interaction extraction systems that are more robust in environments where there is a significant mismatch between training and test conditions.Comment: Appearing in Proceedings of the Thirtieth AAAI Conference on Artificial Intelligence (AAAI-16

BioRED: A Comprehensive Biomedical Relation Extraction Dataset

Automated relation extraction (RE) from biomedical literature is critical for many downstream text mining applications in both research and real-world settings. However, most existing benchmarking datasets for bio-medical RE only focus on relations of a single type (e.g., protein-protein interactions) at the sentence level, greatly limiting the development of RE systems in biomedicine. In this work, we first review commonly used named entity recognition (NER) and RE datasets. Then we present BioRED, a first-of-its-kind biomedical RE corpus with multiple entity types (e.g., gene/protein, disease, chemical) and relation pairs (e.g., gene-disease; chemical-chemical), on a set of 600 PubMed articles. Further, we label each relation as describing either a novel finding or previously known background knowledge, enabling automated algorithms to differentiate between novel and background information. We assess the utility of BioRED by benchmarking several existing state-of-the-art methods, including BERT-based models, on the NER and RE tasks. Our results show that while existing approaches can reach high performance on the NER task (F-score of 89.3%), there is much room for improvement for the RE task, especially when extracting novel relations (F-score of 47.7%). Our experiments also demonstrate that such a comprehensive dataset can successfully facilitate the development of more accurate, efficient, and robust RE systems for biomedicine

Discovering gene functional relationships using FAUN (Feature Annotation Using Nonnegative matrix factorization)

Background Searching the enormous amount of information available in biomedical literature to extract novel functional relationships among genes remains a challenge in the field of bioinformatics. While numerous (software) tools have been developed to extract and identify gene relationships from biological databases, few effectively deal with extracting new (or implied) gene relationships, a process which is useful in interpretation of discovery-oriented genome-wide experiments. Results In this study, we develop a Web-based bioinformatics software environment called FAUN or Feature Annotation Using Nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. FAUN is tested on three manually constructed gene document collections. Its utility and performance as a knowledge discovery tool is demonstrated using a set of genes associated with Autism. Conclusions FAUN not only assists researchers to use biomedical literature efficiently, but also provides utilities for knowledge discovery. This Web-based software environment may be useful for the validation and analysis of functional associations in gene subsets identified by high-throughput experiments

Discovering gene functional relationships using a literature-based NMF model

The rapid growth of the biomedical literature and genomic information presents a major challenge for determining the functional relationships among genes. Several bioinformatics tools have been developed to extract and identify gene relationships from various biological databases. However, an intuitive user-interface tool that allows the biologist to determine functional relationships among genes is still not available. In this study, we develop a Web-based bioinformatics software environment called FAUN or Feature Annotation Using Nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. We tested FAUN on three manually constructed gene document collections, and then used it to analyze several microarray-derived gene sets obtained from studies of the developing cerebellum in normal and mutant mice. FAUN provides utilities for collaborative knowledge discovery and identification of new gene relationships from text streams and repositories (e.g., MEDLINE). It is particularly useful for the validation and analysis of gene associations suggested by microarray experimentation. The FAUN site is publicly available at http://grits.eecs.utk.edu/faun

Text Mining and Gene Expression Analysis Towards Combined Interpretation of High Throughput Data

Microarrays can capture gene expression activity for thousands of genes simultaneously and thus make it possible to analyze cell physiology and disease processes on molecular level. The interpretation of microarray gene expression experiments profits from knowledge on the analyzed genes and proteins and the biochemical networks in which they play a role. The trend is towards the development of data analysis methods that integrate diverse data types. Currently, the most comprehensive biomedical knowledge source is a large repository of free text articles. Text mining makes it possible to automatically extract and use information from texts. This thesis addresses two key aspects, biomedical text mining and gene expression data analysis, with the focus on providing high-quality methods and data that contribute to the development of integrated analysis approaches. The work is structured in three parts. Each part begins by providing the relevant background, and each chapter describes the developed methods as well as applications and results. Part I deals with biomedical text mining: Chapter 2 summarizes the relevant background of text mining; it describes text mining fundamentals, important text mining tasks, applications and particularities of text mining in the biomedical domain, and evaluation issues. In Chapter 3, a method for generating high-quality gene and protein name dictionaries is described. The analysis of the generated dictionaries revealed important properties of individual nomenclatures and the used databases (Fundel and Zimmer, 2006). The dictionaries are publicly available via a Wiki, a web service, and several client applications (Szugat et al., 2005). In Chapter 4, methods for the dictionary-based recognition of gene and protein names in texts and their mapping onto unique database identifiers are described. These methods make it possible to extract information from texts and to integrate text-derived information with data from other sources. Three named entity identification systems have been set up, two of them building upon the previously existing tool ProMiner (Hanisch et al., 2003). All of them have shown very good performance in the BioCreAtIvE challenges (Fundel et al., 2005a; Hanisch et al., 2005; Fundel and Zimmer, 2007). In Chapter 5, a new method for relation extraction (Fundel et al., 2007) is presented. It was applied on the largest collection of biomedical literature abstracts, and thus a comprehensive network of human gene and protein relations has been generated. A classification approach (Küffner et al., 2006) can be used to specify relation types further; e. g., as activating, direct physical, or gene regulatory relation. Part II deals with gene expression data analysis: Gene expression data needs to be processed so that differentially expressed genes can be identified. Gene expression data processing consists of several sequential steps. Two important steps are normalization, which aims at removing systematic variances between measurements, and quantification of differential expression by p-value and fold change determination. Numerous methods exist for these tasks. Chapter 6 describes the relevant background of gene expression data analysis; it presents the biological and technical principles of microarrays and gives an overview of the most relevant data processing steps. Finally, it provides a short introduction to osteoarthritis, which is in the focus of the analyzed gene expression data sets. In Chapter 7, quality criteria for the selection of normalization methods are described, and a method for the identification of differentially expressed genes is proposed, which is appropriate for data with large intensity variances between spots representing the same gene (Fundel et al., 2005b). Furthermore, a system is described that selects an appropriate combination of feature selection method and classifier, and thus identifies genes which lead to good classification results and show consistent behavior in different sample subgroups (Davis et al., 2006). The analysis of several gene expression data sets dealing with osteoarthritis is described in Chapter 8. This chapter contains the biomedical analysis of relevant disease processes and distinct disease stages (Aigner et al., 2006a), and a comparison of various microarray platforms and osteoarthritis models. Part III deals with integrated approaches and thus provides the connection between parts I and II: Chapter 9 gives an overview of different types of integrated data analysis approaches, with a focus on approaches that integrate gene expression data with manually compiled data, large-scale networks, or text mining. In Chapter 10, a method for the identification of genes which are consistently regulated and have a coherent literature background (Küffner et al., 2005) is described. This method indicates how gene and protein name identification and gene expression data can be integrated to return clusters which contain genes that are relevant for the respective experiment together with literature information that supports interpretation. Finally, in Chapter 11 ideas on how the described methods can contribute to current research and possible future directions are presented

Doctor of Philosophy

dissertationMedical knowledge learned in medical school can become quickly outdated given the tremendous growth of the biomedical literature. It is the responsibility of medical practitioners to continuously update their knowledge with recent, best available clinical evidence to make informed decisions about patient care. However, clinicians often have little time to spend on reading the primary literature even within their narrow specialty. As a result, they often rely on systematic evidence reviews developed by medical experts to fulfill their information needs. At the present, systematic reviews of clinical research are manually created and updated, which is expensive, slow, and unable to keep up with the rapidly growing pace of medical literature. This dissertation research aims to enhance the traditional systematic review development process using computer-aided solutions. The first study investigates query expansion and scientific quality ranking approaches to enhance literature search on clinical guideline topics. The study showed that unsupervised methods can improve retrieval performance of a popular biomedical search engine (PubMed). The proposed methods improve the comprehensiveness of literature search and increase the ratio of finding relevant studies with reduced screening effort. The second and third studies aim to enhance the traditional manual data extraction process. The second study developed a framework to extract and classify texts from PDF reports. This study demonstrated that a rule-based multipass sieve approach is more effective than a machine-learning approach in categorizing document-level structures and iv that classifying and filtering publication metadata and semistructured texts enhances the performance of an information extraction system. The proposed method could serve as a document processing step in any text mining research on PDF documents. The third study proposed a solution for the computer-aided data extraction by recommending relevant sentences and key phrases extracted from publication reports. This study demonstrated that using a machine-learning classifier to prioritize sentences for specific data elements performs equally or better than an abstract screening approach, and might save time and reduce errors in the full-text screening process. In summary, this dissertation showed that there are promising opportunities for technology enhancement to assist in the development of systematic reviews. In this modern age when computing resources are getting cheaper and more powerful, the failure to apply computer technologies to assist and optimize the manual processes is a lost opportunity to improve the timeliness of systematic reviews. This research provides methodologies and tests hypotheses, which can serve as the basis for further large-scale software engineering projects aimed at fully realizing the prospect of computer-aided systematic reviews

Identification of Informativeness in Text using Natural Language Stylometry

In this age of information overload, one experiences a rapidly growing over-abundance of written text. To assist with handling this bounty, this plethora of texts is now widely used to develop and optimize statistical natural language processing (NLP) systems. Surprisingly, the use of more fragments of text to train these statistical NLP systems may not necessarily lead to improved performance. We hypothesize that those fragments that help the most with training are those that contain the desired information. Therefore, determining informativeness in text has become a central issue in our view of NLP. Recent developments in this field have spawned a number of solutions to identify informativeness in text. Nevertheless, a shortfall of most of these solutions is their dependency on the genre and domain of the text. In addition, most of them are not efficient regardless of the natural language processing problem areas. Therefore, we attempt to provide a more general solution to this NLP problem. This thesis takes a different approach to this problem by considering the underlying theme of a linguistic theory known as the Code Quantity Principle. This theory suggests that humans codify information in text so that readers can retrieve this information more efficiently. During the codification process, humans usually change elements of their writing ranging from characters to sentences. Examples of such elements are the use of simple words, complex words, function words, content words, syllables, and so on. This theory suggests that these elements have reasonable discriminating strength and can play a key role in distinguishing informativeness in natural language text. In another vein, Stylometry is a modern method to analyze literary style and deals largely with the aforementioned elements of writing. With this as background, we model text using a set of stylometric attributes to characterize variations in writing style present in it. We explore their effectiveness to determine informativeness in text. To the best of our knowledge, this is the first use of stylometric attributes to determine informativeness in statistical NLP. In doing so, we use texts of different genres, viz., scientific papers, technical reports, emails and newspaper articles, that are selected from assorted domains like agriculture, physics, and biomedical science. The variety of NLP systems that have benefitted from incorporating these stylometric attributes somewhere in their computational realm dealing with this set of multifarious texts suggests that these attributes can be regarded as an effective solution to identify informativeness in text. In addition to the variety of text genres and domains, the potential of stylometric attributes is also explored in some NLP application areas---including biomedical relation mining, automatic keyphrase indexing, spam classification, and text summarization---where performance improvement is both important and challenging. The success of the attributes in all these areas further highlights their usefulness

Deep Neural Architectures for End-to-End Relation Extraction

The rapid pace of scientific and technological advancements has led to a meteoric growth in knowledge, as evidenced by a sharp increase in the number of scholarly publications in recent years. PubMed, for example, archives more than 30 million biomedical articles across various domains and covers a wide range of topics including medicine, pharmacy, biology, and healthcare. Social media and digital journalism have similarly experienced their own accelerated growth in the age of big data. Hence, there is a compelling need for ways to organize and distill the vast, fragmented body of information (often unstructured in the form of natural human language) so that it can be assimilated, reasoned about, and ultimately harnessed. Relation extraction is an important natural language task toward that end. In relation extraction, semantic relationships are extracted from natural human language in the form of (subject, object, predicate) triples such that subject and object are mentions of discrete concepts and predicate indicates the type of relation between them. The difficulty of relation extraction becomes clear when we consider the myriad of ways the same relation can be expressed in natural language. Much of the current works in relation extraction assume that entities are known at extraction time, thus treating entity recognition as an entirely separate and independent task. However, recent studies have shown that entity recognition and relation extraction, when modeled together as interdependent tasks, can lead to overall improvements in extraction accuracy. When modeled in such a manner, the task is referred to as end-to-end relation extraction. In this work, we present four studies that introduce incrementally sophisticated architectures designed to tackle the task of end-to-end relation extraction. In the first study, we present a pipeline approach for extracting protein-protein interactions as affected by particular mutations. The pipeline system makes use of recurrent neural networks for protein detection, lexicons for gene normalization, and convolutional neural networks for relation extraction. In the second study, we show that a multi-task learning framework, with parameter sharing, can achieve state-of-the-art results for drug-drug interaction extraction. At its core, the model uses graph convolutions, with a novel attention-gating mechanism, over dependency parse trees. In the third study, we present a more efficient and general-purpose end-to-end neural architecture designed around the idea of the table-filling paradigm; for an input sentence of length n, all entities and relations are extracted in a single pass of the network in an indirect fashion by populating the cells of a corresponding n by n table using metric-based features. We show that this approach excels in both the general English and biomedical domains with extraction times that are up to an order of magnitude faster compared to the prior best. In the fourth and last study, we present an architecture for relation extraction that, in addition to being end-to-end, is able to handle cross-sentence and N-ary relations. Overall, our work contributes to the advancement of modern information extraction by exploring end-to-end solutions that are fast, accurate, and generalizable to many high-value domains