生物医学领域本体的构建、评估与应用

介绍了本体的概念和基本特点, 总结了领域本体的一般构建流程和评估方法, 并举例说明了生物医学领域本体在生物学对象注释、富集分析、数据整合、数据库构建、图书馆建设、文本挖掘等方面的实际应用情况, 整理了目前常用的生物医学领域本体数据库、本体描述语言和本体编辑软件, 最后探讨了目前生物医学领域本体研究中普遍存在的问题和该领域未来的发展方向.     

Text mining and ontologies in biomedicine: making sense of raw text

The volume of biomedical literature is increasing at such a rate that it is becoming difficult to locate, retrieve and manage the reported information without text mining, which aims to automatically distill information, extract facts, discover implicit links and generate hypotheses relevant to user needs. Ontologies, as conceptual models, provide the necessary framework for semantic representation of textual information. The principal link between text and an ontology is terminology, which maps terms to domain-specific concepts. This paper summarises different approaches in which ontologies have been used for text-mining applications in biomedicine.     

文本挖掘在生物医学领域中的应用文献计量学分析

目的:近年来,随着生物医学领域文献数量的急骤增长,大量隐含的规律和新知被掩埋在浩如烟海的文献之中,而将文本挖掘技术应用于生物医学领域则可以对海量生物医学文献数据进行整合、分析,从而获得有价值的信息,提高人们对生物医学现象的认识。本文就我国近十年来文本挖掘技术在生物医学领域的应用现状进行文献计量学分析,旨在为我国科研工作者对该领域的进一步研究提供参考。方法:对国内正式发表的生物医学领域文本挖掘相关文献进行检索和筛选,分别从年度变化、地区分布、研究机构、期刊来源、研究领域等方面进行分析。结果:国内生物医学文本挖掘文献总量呈上升趋势,主要集中在挖掘算法的研究和文本挖掘技术在中医药及系统生物学领域的应用方面;北京、上海、广东等地的研究处于领先地位。结论:相比其他较为成熟的研究课题来说,目前文本挖掘技术在生物医学中的应用在国内还属于一个比较新的研究领域,但国内对该领域的认识正不断提高、研究正不断深入,初步形成了一批在该领域的核心研究地区、核心研究机构和核心研究领域,而对其进一步的研究,必将为生物医学领域的发展注入新的活力。     

Knowledge acquisition, semantic text mining, and security risks in health and biomedical informatics

Computational techniques have been adopted in medi-cal and biological systems for a long time. There is no doubt that the development and application of computational methods will render great help in better understanding biomedical and biological functions. Large amounts of datasets have been produced by biomedical and biological experiments and simulations. In order for researchers to gain knowledge from origi- nal data, nontrivial transformation is necessary, which is regarded as a critical link in the chain of knowledge acquisition, sharing, and reuse. Challenges that have been encountered include: how to efficiently and effectively represent human knowledge in formal computing models, how to take advantage of semantic text mining techniques rather than traditional syntactic text mining, and how to handle security issues during the knowledge sharing and reuse. This paper summarizes the state-of-the-art in these research directions. We aim to provide readers with an introduction of major computing themes to be applied to the medical and biological research.     

Integrating image data into biomedical text categorization

Categorization of biomedical articles is a central task for supporting various curation efforts. It can also form the basis for effective biomedical text mining. Automatic text classification in the biomedical domain is thus an active research area. Contests organized by the KDD Cup (2002) and the TREC Genomics track (since 2003) defined several annotation tasks that involved document classification, and provided training and test data sets. So far, these efforts focused on analyzing only the text content of documents. However, as was noted in the KDD'02 text mining contest-where figure-captions proved to be an invaluable feature for identifying documents of interest-images often provide curators with critical information. We examine the possibility of using information derived directly from image data, and of integrating it with text-based classification, for biomedical document categorization. We present a method for obtaining features from images and for using them-both alone and in combination with text-to perform the triage task introduced in the TREC Genomics track 2004. The task was to determine which documents are relevant to a given annotation task performed by the Mouse Genome Database curators. We show preliminary results, demonstrating that the method has a strong potential to enhance and complement traditional text-based categorization methods.     

A re-evaluation of biomedical named entity-term relations

Text mining can support the interpretation of the enormous quantity of textual data produced in biomedical field. Recent developments in biomedical text mining include advances in the reliability of the recognition of named entities (NEs) such as specific genes and proteins, as well as movement toward richer representations of the associations of NEs. We argue that this shift in representation should be accompanied by the adoption of a more detailed model of the relations holding between NEs and other relevant domain terms. As a step toward this goal, we study NE-term relations with the aim of defining a detailed, broadly applicable set of relation types based on accepted domain standard concepts for use in corpus annotation and domain information extraction approaches.     

Hairpins in bookstacks: information retrieval from biomedical text

Current advances in high-throughput biology are accompanied by a tremendous increase in the number of related publications. Much biomedical information is reported in the vast amount of literature. The ability to rapidly and effectively survey the literature is necessary for both the design and the interpretation of large-scale experiments, and for curation of structured biomedical knowledge in public databases. Given the millions of published documents, the field of information retrieval, which is concerned with the automatic identification of relevant documents from large text collections, has much to offer. This paper introduces the basics of information retrieval, discusses its applications in biomedicine, and presents traditional and non-traditional ways in which it can be used.     

The landscape for epigenetic/epigenomic biomedical resources

Recent advances in molecular biology and computational power have seen the biomedical sector enter a new era, with corresponding development of Bioinformatics as a major discipline. Generation of enormous amounts of data has driven the need for more advanced storage solutions and shared access through a range of public repositories. The number of such biomedical resources is increasing constantly and mining these large and diverse data sets continues to present real challenges. This paper attempts a general overview of currently available resources, together with remarks on their data mining and analysis capabilities. Of interest here is the recent shift in focus from genetic to epigenetic/epigenomic research and the emergence and extension of resource provision to support this both at local and global scale. Biomedical text and numerical data mining are both considered, the first dealing with automated methods for analyzing research content and information extraction, and the second (broadly) with pattern recognition and prediction. Any summary and selection of resources is inherently limited, given the spectrum available, but the aim is to provide a guideline for the assessment and comparison of currently available provision, particularly as this relates to epigenetics/epigenomics.     

The landscape for epigenetic/epigenomic biomedical resources

Recent advances in molecular biology and computational power have seen the biomedical sector enter a new era, with corresponding development of Bioinformatics as a major discipline. Generation of enormous amounts of data has driven the need for more advanced storage solutions and shared access through a range of public repositories. The number of such biomedical resources is increasing constantly and mining these large and diverse data sets continues to present real challenges. This paper attempts a general overview of currently available resources, together with remarks on their data mining and analysis capabilities. Of interest here is the recent shift in focus from genetic to epigenetic/epigenomic research and the emergence and extension of resource provision to support this both at local and global scale. Biomedical text and numerical data mining are both considered, the first dealing with automated methods for analyzing research content and information extraction, and the second (broadly) with pattern recognition and prediction. Any summary and selection of resources is inherently limited, given the spectrum available, but the aim is to provide a guideline for the assessment and comparison of currently available provision, particularly as this relates to epigenetics/epigenomics.     

New directions in biomedical text annotation: definitions, guidelines and corpus construction

Background  

While biomedical text mining is emerging as an important research area, practical results have proven difficult to achieve. We believe that an important first step towards more accurate text-mining lies in the ability to identify and characterize text that satisfies various types of information needs. We report here the results of our inquiry into properties of scientific text that have sufficient generality to transcend the confines of a narrow subject area, while supporting practical mining of text for factual information. Our ultimate goal is to annotate a significant corpus of biomedical text and train machine learning methods to automatically categorize such text along certain dimensions that we have defined.     

A text mining analysis of the climate change literature in industrial ecology

The literature on climate change research has evolved tremendously since the 1990s. The goal of this study is to use text mining to review the climate change literature and study the evolution of the main trends over time. Specific keywords from articles published in the special issue “ Industrial Ecology for Climate Change Adaptation and Resilience” in the Journal of Industrial Ecology are first selected. Details of over 35,000 publications containing these keywords are downloaded from the Web of Science from 1990 to 2018. The number of publications and co‐occurrence of keywords are analyzed. Moreover, latent Dirichlet allocation (LDA)—a probabilistic approach that can retrieve topics from large and unstructured text documents—is applied on the abstracts to uncover the main topics (consisting of new terms) that naturally emerge from them. The evolution in time of the importance of some emerging topics is then analyzed on the basis of their relative frequency. Overall, a rapid growth in climate change publications is observed. Terms such as “climate change adaptation” appear on the rise, whereas other terms are declining such as “pollution.” Moreover, several terms tend to co‐occur frequently, such as “climate change adaptation” and “resilience.” The database collected and the LiTCoF (Literature Topic Co‐occurrence and Frequency) Python‐based tool developed for this study are also made openly accessible. This article met the requirements for a gold – gold JIE data openness badge described http://jie.click/badges .     

Functional gene clustering via gene annotation sentences, MeSH and GO keywords from biomedical literature

Gene function annotation remains a key challenge in modern biology. This is especially true for high-throughput techniques such as gene expression experiments. Vital information about genes is available electronically from biomedical literature in the form of full texts and abstracts. In addition, various publicly available databases (such as GenBank, Gene Ontology and Entrez) provide access to gene-related information at different levels of biological organization, granularity and data format. This information is being used to assess and interpret the results from high-throughput experiments. To improve keyword extraction for annotational clustering and other types of analyses, we have developed a novel text mining approach, which is based on keywords identified at the level of gene annotation sentences (in particular sentences characterizing biological function) instead of entire abstracts. Further, to improve the expressiveness and usefulness of gene annotation terms, we investigated the combination of sentence-level keywords with terms from the Medical Subject Headings (MeSH) and Gene Ontology (GO) resources. We find that sentence-level keywords combined with MeSH terms outperforms the typical 'baseline' set-up (term frequencies at the level of abstracts) by a significant margin, whereas the addition of GO terms improves matters only marginally. We validated our approach on the basis of a manually annotated corpus of 200 abstracts generated on the basis of 2 cancer categories and 10 genes per category. We applied the method in the context of three sets of differentially expressed genes obtained from pediatric brain tumor samples. This analysis suggests novel interpretations of discovered gene expression patterns.     

A comparative study of cells in inflammation,EAE and MS using biomedical literature data mining

Summary Biomedical literature and database annotations, available in electronic forms, contain a vast amount of knowledge resulting from global research. Users, attempting to utilize the current state-of-the-art research results are frequently overwhelmed by the volume of such information, making it difficult and time-consuming to locate the relevant knowledge. Literature mining, data mining, and domain specific knowledge integration techniques can be effectively used to provide a user-centric view of the information in a real-world biological problem setting. Bioinformatics tools that are based on real-world problems can provide varying levels of information content, bridging the gap between biomedical and bioinformatics research. We have developed a user-centric bioinformatics research tool, called BioMap, that can provide a customized, adaptive view of the information and knowledge space. BioMap was validated by using inflammatory diseases as a problem domain to identify and elucidate the associations among cells and cellular components involved in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). The BioMap system was able to demonstrate the associations between cells directly excavated from biomedical literature for inflammation, EAE and MS. These association graphs followed the scale-free network behavior (average γ = 2.1) that are commonly found in biological networks.     

A cascaded approach to normalising gene mentions in biomedical literature

Linking gene and protein names mentioned in the literature to unique identifiers in referent genomic databases is an essential step in accessing and integrating knowledge in the biomedical domain. However, it remains a challenging task due to lexical and terminological variation, and ambiguity of gene name mentions in documents. We present a generic and effective rule-based approach to link gene mentions in the literature to referent genomic databases, where pre-processing of both gene synonyms in the databases and gene mentions in text are first applied. The mapping method employs a cascaded approach, which combines exact, exact-like and token-based approximate matching by using flexible representations of a gene synonym dictionary and gene mentions generated during the pre-processing phase. We also consider multi-gene name mentions and permutation of components in gene names. A systematic evaluation of the suggested methods has identified steps that are beneficial for improving either precision or recall in gene name identification. The results of the experiments on the BioCreAtIvE2 data sets (identification of human gene names) demonstrated that our methods achieved highly encouraging results with F-measure of up to 81.20%.     

Conceptual biology,hypothesis discovery,and text mining: Swanson's legacy

Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.     

BCC-NER: bidirectional,contextual clues named entity tagger for gene/protein mention recognition

Tagging biomedical entities such as gene, protein, cell, and cell-line is the first step and an important pre-requisite in biomedical literature mining. In this paper, we describe our hybrid named entity tagging approach namely BCC-NER (bidirectional, contextual clues named entity tagger for gene/protein mention recognition). BCC-NER is deployed with three modules. The first module is for text processing which includes basic NLP pre-processing, feature extraction, and feature selection. The second module is for training and model building with bidirectional conditional random fields (CRF) to parse the text in both directions (forward and backward) and integrate the backward and forward trained models using margin-infused relaxed algorithm (MIRA). The third and final module is for post-processing to achieve a better performance, which includes surrounding text features, parenthesis mismatching, and two-tier abbreviation algorithm. The evaluation results on BioCreative II GM test corpus of BCC-NER achieve a precision of 89.95, recall of 84.15 and overall F-score of 86.95, which is higher than the other currently available open source taggers.     

A web service for biomedical term look-up

Recent years have seen a huge increase in the amount of biomedical information that is available in electronic format. Consequently, for biomedical researchers wishing to relate their experimental results to relevant data lurking somewhere within this expanding universe of on-line information, the ability to access and navigate biomedical information sources in an efficient manner has become increasingly important. Natural language and text processing techniques can facilitate this task by making the information contained in textual resources such as MEDLINE more readily accessible and amenable to computational processing. Names of biological entities such as genes and proteins provide critical links between different biomedical information sources and researchers' experimental data. Therefore, automatic identification and classification of these terms in text is an essential capability of any natural language processing system aimed at managing the wealth of biomedical information that is available electronically. To support term recognition in the biomedical domain, we have developed Termino, a large-scale terminological resource for text processing applications, which has two main components: first, a database into which very large numbers of terms can be loaded from resources such as UMLS, and stored together with various kinds of relevant information; second, a finite state recognizer, for fast and efficient identification and mark-up of terms within text. Since many biomedical applications require this functionality, we have made Termino available to the community as a web service, which allows for its integration into larger applications as a remotely located component, accessed through a standardized interface over the web.     

一种基于MeSH主题词的临床?鄄组学关系挖掘方法

癌症的发生发展与机体内基因的改变有密切联系,在临床上表现为症状或检测指标的异常．通过挖掘分析临床表现与基因改变之间的关系,可为癌症早期诊断和精准治疗提供临床决策支持．从文献数据出发,利用结论性数据挖掘基因与临床表现的关系具有重要意义．本文提出一种基于医学主题词(Medical Subject Headings,MeSH)的生物医学实体关系挖掘方法．该方法利用PubMed中提供的文献信息,借用向量空间模型思想,使用MeSH主题词矢量表达待研究实体,引入文献相互引用因素对结果进行修正,将关系挖掘转化为矢量间的数学运算,实现定量分析．本文将该方法应用于结直肠癌临床表现和基因关系的研究中,得到与结直肠癌相关的203个基因和对应的临床-基因462个关系．通过结合使用基因功能和通路分析工具g:Profiler和KEGG等,对结果进行分析验证．结果表明,基于MeSH主题词的文献挖掘方法,避免传统“共现”方法对发现潜在关系的限制和复杂语义分析带来的大量计算,为生物实体之间潜在关系的挖掘提供一种新的思路和方法．     

Machine learning and word sense disambiguation in the biomedical domain: design and evaluation issues

Background  

Word sense disambiguation (WSD) is critical in the biomedical domain for improving the precision of natural language processing (NLP), text mining, and information retrieval systems because ambiguous words negatively impact accurate access to literature containing biomolecular entities, such as genes, proteins, cells, diseases, and other important entities. Automated techniques have been developed that address the WSD problem for a number of text processing situations, but the problem is still a challenging one. Supervised WSD machine learning (ML) methods have been applied in the biomedical domain and have shown promising results, but the results typically incorporate a number of confounding factors, and it is problematic to truly understand the effectiveness and generalizability of the methods because these factors interact with each other and affect the final results. Thus, there is a need to explicitly address the factors and to systematically quantify their effects on performance.