Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Visualizing a Field of Research: A Methodology of Systematic Scientometric Reviews

Systematic scientometric reviews, empowered by scientometric and visual analytic techniques, offer opportunities to improve the timeliness, accessibility, and reproducibility of conventional systematic reviews. While increasingly accessible science mapping tools enable end users to visualize the structure and dynamics of a research field, a common bottleneck in the current practice is the construction of a collection of scholarly publications as the input of the subsequent scientometric analysis and visualization. End users often have to face a dilemma in the preparation process: the more they know about a knowledge domain, the easier it is for them to find the relevant data to meet their needs adequately; the little they know, the harder the problem is. What can we do to avoid missing something valuable but beyond our initial description? In this article, we introduce a flexible and generic methodology, cascading citation expansion, to increase the quality of constructing a bibliographic dataset for systematic reviews. Furthermore, the methodology simplifies the conceptualization of globalism and localism in science mapping and unifies them on a consistent and continuous spectrum. We demonstrate an application of the methodology to the research of literature-based discovery and compare five datasets constructed based on three use scenarios, namely a conventional keyword-based search (one dataset), an expansion process starting with a groundbreaking article of the knowledge domain (two datasets), and an expansion process starting with a recently published review article by a prominent expert in the domain (two datasets). The unique coverage of each of the datasets is inspected through network visualization overlays with reference to other datasets in a broad and integrated context.Comment: 17 figures, 3 table

Automatically Identifying Gene/Protein Terms in MEDLINE Abstracts

Motivation. Natural language processing (NLP) techniques are used to extract information automatically from computer-readable literature. In biology, the identification of terms corresponding to biological substances (e.g., genes and proteins) is a necessary step that precedes the application of other NLP systems that extract biological information (e.g., protein–protein interactions, gene regulation events, and biochemical pathways). We have developed GPmarkup (for “gene/protein-full name mark up”), a software system that automatically identifies gene/protein terms (i.e., symbols or full names) in MEDLINE abstracts. As a part of marking up process, we also generated automatically a knowledge source of paired gene/protein symbols and full names (e.g., LARD for lymphocyte associated receptor of death) from MEDLINE. We found that many of the pairs in our knowledge source do not appear in the current GenBank database. Therefore our methods may also be used for automatic lexicon generation. Results. GPmarkup has 73% recall and 93% precision in identifying and marking up gene/protein terms in MEDLINE abstracts.Availability: A random sample of gene/protein symbols and full names and a sample set of marked up abstracts can be viewed at http://www.cpmc.columbia.edu/homepages/yuh9001/GPmarkup/

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

Understanding PubMed Search Results using Topic Models and Interactive Information Visualization

With data increasing exponentially, extracting and understanding information, themes and relationships from larger collections of documents is becoming more and more important to researchers in many areas. PubMed, which comprises more than 25 million citations, uses Medical Subject Headings (MeSH) to index articles to better facilitate their management, searching and indexing. However, researchers are still challenged to find and then get a meaningful overview of a set of documents in a specific area of interest. This is due in part to several limitations of MeSH terms, including: the need to monitor and expand the vocabulary; the lack of concept coverage for newly developing areas; human inconsistency in assigning codes; and the time required to manually index an exponentially growing corpus. Another reason for this challenge is that neither PubMed itself nor its related Web tools can help users see high level themes and hidden semantic structures in the biomedical literature. Topic models are a class of statistical machine learning algorithms that when given a set of natural language documents, extract the semantic themes (topics) from the set of documents, describe the topics for each document, and the semantic similarity of topics and documents. Researchers have shown that these latent themes can help humans better understand and search documents. Unlike MeSH terms, which are created based on important concepts throughout the literature, topics extracted from a subset of documents are specific to those documents. Thus they can find document-specific themes that may not exist in MeSH terms. Such themes may give a subject area-specific set of themes for browsing search results, and provide a broader overview of the search results. This first part of this dissertation presents the TopicalMeSH representation, which exploits the ‘correspondence’ between topics generated using latent Dirichlet allocation (LDA) and MeSH terms to create new document representations that combine MeSH terms and latent topic vectors. In an evaluation with 15 systematic drug review corpora, TopicalMeSH performed better than MeSH in both document retrieval and classification tasks. The second part of this work introduces the “Hybrid Topic”, an alternative LDA approach that uses a ‘bag-of-MeSH&words’ approach, instead of just ‘bag-of-words’, to test whether the addition of labels (e.g. MeSH descriptors) can improve the quality and facilitate the interpretation of LDA-generated topics. An evaluation of this approach on the quality and interpretability of topics in both a general corpus and a specialized corpus demonstrated that the coherence of ‘hybrid topics’ is higher than that of regular bag-of-words topics in both specialized and general copora. The last part of this dissertation presents a visualization tool based on the ‘hybrid topics’ model that could allow users to interactively use topic models and MeSH terms to efficiently and effectively retrieve relevant information from tons of PubMed search results. A preliminary user study has been conducted with 6 participants. All of them agree that this tool can quickly help them understand PubMed search results and identify target articles