Identifying genetic variants that affect drug response or play a role in disease is an important task for clinicians and researchers. Before individual variants can be explored efficiently for effect on drug response or disease relationships, specific candidate genes must be identified. While many methods rank candidate genes through the use of sequence features and network topology, only a few exploit the information contained in the biomedical literature. In this work, we train and test a classifier on known pharmacogenes from PharmGKB and present a classifier that predicts pharmacogenes on a genome-wide scale using only Gene Ontology annotations and simple features mined from the biomedical literature. Performance of F=0.86, AUC=0.860 is achieved. The top 10 predicted genes are analyzed. Additionally, a set of enriched pharmacogenic Gene Ontology concepts is produced.
Ontological concepts are useful for many different biomedical tasks. Concepts are difficult to recognize in text due to a disconnect between what is captured in an ontology and how the concepts are expressed in text. There are many recognizers for specific ontologies, but a general approach for concept recognition is an open problem.
Three dictionary-based systems (MetaMap, NCBO Annotator, and ConceptMapper) are evaluated on eight biomedical ontologies in the Colorado Richly Annotated Full-Text (CRAFT) Corpus. Over 1,000 parameter combinations are examined, and best-performing parameters for each system-ontology pair are presented.
Baselines for concept recognition by three systems on eight biomedical ontologies are established (F-measures range from 0.14–0.83). Out of the three systems we tested, ConceptMapper is generally the best-performing system; it produces the highest F-measure of seven out of eight ontologies. Default parameters are not ideal for most systems on most ontologies; by changing parameters F-measure can be increased by up to 0.4. Not only are best performing parameters presented, but suggestions for choosing the best parameters based on ontology characteristics are presented.
The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed.
BioHackathon; Bioinformatics; Semantic Web; Web services; Ontology; Visualization; Knowledge representation; Databases; Semantic interoperability; Data models; Data sharing; Data integration
This article surveys efforts on text mining of the pharmacogenomics literature, mainly from the period 2008 to 2011. Pharmacogenomics (or pharmacogenetics) is the field that studies how human genetic variation impacts drug response. Therefore, publications span the intersection of research in genotypes, phenotypes and pharmacology, a topic that has increasingly become a focus of active research in recent years. This survey covers efforts dealing with the automatic recognition of relevant named entities (e.g. genes, gene variants and proteins, diseases and other pathological phenomena, drugs and other chemicals relevant for medical treatment), as well as various forms of relations between them. A wide range of text genres is considered, such as scientific publications (abstracts, as well as full texts), patent texts and clinical narratives. We also discuss infrastructure and resources needed for advanced text analytics, e.g. document corpora annotated with corresponding semantic metadata (gold standards and training data), biomedical terminologies and ontologies providing domain-specific background knowledge at different levels of formality and specificity, software architectures for building complex and scalable text analytics pipelines and Web services grounded to them, as well as comprehensive ways to disseminate and interact with the typically huge amounts of semiformal knowledge structures extracted by text mining tools. Finally, we consider some of the novel applications that have already been developed in the field of pharmacogenomic text mining and point out perspectives for future research.
text mining; information extraction; knowledge discovery from texts; text analytics; biomedical natural language processing; pharmacogenomics; pharmacogenetics
Text mining for translational bioinformatics is a new field with tremendous research potential. It is a subfield of biomedical natural language processing that concerns itself directly with the problem of relating basic biomedical research to clinical practice, and vice versa. Applications of text mining fall both into the category of T1 translational research—translating basic science results into new interventions—and T2 translational research, or translational research for public health. Potential use cases include better phenotyping of research subjects, and pharmacogenomic research. A variety of methods for evaluating text mining applications exist, including corpora, structured test suites, and post hoc judging. Two basic principles of linguistic structure are relevant for building text mining applications. One is that linguistic structure consists of multiple levels. The other is that every level of linguistic structure is characterized by ambiguity. There are two basic approaches to text mining: rule-based, also known as knowledge-based; and machine-learning-based, also known as statistical. Many systems are hybrids of the two approaches. Shared tasks have had a strong effect on the direction of the field. Like all translational bioinformatics software, text mining software for translational bioinformatics can be considered health-critical and should be subject to the strictest standards of quality assurance and software testing.
In many databases, biocuration primarily involves literature curation, which usually involves retrieving relevant articles, extracting information that will translate into annotations and identifying new incoming literature. As the volume of biological literature increases, the use of text mining to assist in biocuration becomes increasingly relevant. A number of groups have developed tools for text mining from a computer science/linguistics perspective, and there are many initiatives to curate some aspect of biology from the literature. Some biocuration efforts already make use of a text mining tool, but there have not been many broad-based systematic efforts to study which aspects of a text mining tool contribute to its usefulness for a curation task. Here, we report on an effort to bring together text mining tool developers and database biocurators to test the utility and usability of tools. Six text mining systems presenting diverse biocuration tasks participated in a formal evaluation, and appropriate biocurators were recruited for testing. The performance results from this evaluation indicate that some of the systems were able to improve efficiency of curation by speeding up the curation task significantly (∼1.7- to 2.5-fold) over manual curation. In addition, some of the systems were able to improve annotation accuracy when compared with the performance on the manually curated set. In terms of inter-annotator agreement, the factors that contributed to significant differences for some of the systems included the expertise of the biocurator on the given curation task, the inherent difficulty of the curation and attention to annotation guidelines. After the task, annotators were asked to complete a survey to help identify strengths and weaknesses of the various systems. The analysis of this survey highlights how important task completion is to the biocurators’ overall experience of a system, regardless of the system’s high score on design, learnability and usability. In addition, strategies to refine the annotation guidelines and systems documentation, to adapt the tools to the needs and query types the end user might have and to evaluate performance in terms of efficiency, user interface, result export and traditional evaluation metrics have been analyzed during this task. This analysis will help to plan for a more intense study in BioCreative IV.
Manually annotated corpora are critical for the training and evaluation of automated methods to identify concepts in biomedical text.
This paper presents the concept annotations of the Colorado Richly Annotated Full-Text (CRAFT) Corpus, a collection of 97 full-length, open-access biomedical journal articles that have been annotated both semantically and syntactically to serve as a research resource for the biomedical natural-language-processing (NLP) community. CRAFT identifies all mentions of nearly all concepts from nine prominent biomedical ontologies and terminologies: the Cell Type Ontology, the Chemical Entities of Biological Interest ontology, the NCBI Taxonomy, the Protein Ontology, the Sequence Ontology, the entries of the Entrez Gene database, and the three subontologies of the Gene Ontology. The first public release includes the annotations for 67 of the 97 articles, reserving two sets of 15 articles for future text-mining competitions (after which these too will be released). Concept annotations were created based on a single set of guidelines, which has enabled us to achieve consistently high interannotator agreement.
As the initial 67-article release contains more than 560,000 tokens (and the full set more than 790,000 tokens), our corpus is among the largest gold-standard annotated biomedical corpora. Unlike most others, the journal articles that comprise the corpus are drawn from diverse biomedical disciplines and are marked up in their entirety. Additionally, with a concept-annotation count of nearly 100,000 in the 67-article subset (and more than 140,000 in the full collection), the scale of conceptual markup is also among the largest of comparable corpora. The concept annotations of the CRAFT Corpus have the potential to significantly advance biomedical text mining by providing a high-quality gold standard for NLP systems. The corpus, annotation guidelines, and other associated resources are freely available at http://bionlp-corpora.sourceforge.net/CRAFT/index.shtml.
Molecular biology has become heavily dependent on biological knowledge encoded in expert curated biological databases. As the volume of biological literature increases, biocurators need help in keeping up with the literature; (semi-) automated aids for biocuration would seem to be an ideal application for natural language processing and text mining. However, to date, there have been few documented successes for improving biocuration throughput using text mining. Our initial investigations took place for the workshop on ‘Text Mining for the BioCuration Workflow’ at the third International Biocuration Conference (Berlin, 2009). We interviewed biocurators to obtain workflows from eight biological databases. This initial study revealed high-level commonalities, including (i) selection of documents for curation; (ii) indexing of documents with biologically relevant entities (e.g. genes); and (iii) detailed curation of specific relations (e.g. interactions); however, the detailed workflows also showed many variabilities. Following the workshop, we conducted a survey of biocurators. The survey identified biocurator priorities, including the handling of full text indexed with biological entities and support for the identification and prioritization of documents for curation. It also indicated that two-thirds of the biocuration teams had experimented with text mining and almost half were using text mining at that time. Analysis of our interviews and survey provide a set of requirements for the integration of text mining into the biocuration workflow. These can guide the identification of common needs across curated databases and encourage joint experimentation involving biocurators, text mining developers and the larger biomedical research community.
This paper reports on a shared task involving the assignment of emotions to suicide notes. Two features distinguished this task from previous shared tasks in the biomedical domain. One is that it resulted in the corpus of fully anonymized clinical text and annotated suicide notes. This resource is permanently available and will (we hope) facilitate future research. The other key feature of the task is that it required categorization with respect to a large set of labels. The number of participants was larger than in any previous biomedical challenge task. We describe the data production process and the evaluation measures, and give a preliminary analysis of the results. Many systems performed at levels approaching the inter-coder agreement, suggesting that human-like performance on this task is within the reach of currently available technologies.
Sentiment analysis; suicide; suicide notes; natural language processing; computational linguistics; shared task; challenge 2011
The contents of parentheses in biomedical text have many potential uses in text mining applications. However, making use of them requires the ability to determine what class of contents they are. A system that automatically classifies parenthesized text into one of 20 categories is presented and evaluated here. It performs at a micro-averaged accuracy of 68% and a macro-averaged accuracy of 60% on an annotated corpus. The application is available as a Java class and as a Perl module.
An increase in work on the full text of journal articles and the growth of PubMedCentral have the opportunity to create a major paradigm shift in how biomedical text mining is done. However, until now there has been no comprehensive characterization of how the bodies of full text journal articles differ from the abstracts that until now have been the subject of most biomedical text mining research.
We examined the structural and linguistic aspects of abstracts and bodies of full text articles, the performance of text mining tools on both, and the distribution of a variety of semantic classes of named entities between them. We found marked structural differences, with longer sentences in the article bodies and much heavier use of parenthesized material in the bodies than in the abstracts. We found content differences with respect to linguistic features. Three out of four of the linguistic features that we examined were statistically significantly differently distributed between the two genres. We also found content differences with respect to the distribution of semantic features. There were significantly different densities per thousand words for three out of four semantic classes, and clear differences in the extent to which they appeared in the two genres. With respect to the performance of text mining tools, we found that a mutation finder performed equally well in both genres, but that a wide variety of gene mention systems performed much worse on article bodies than they did on abstracts. POS tagging was also more accurate in abstracts than in article bodies.
Aspects of structure and content differ markedly between article abstracts and article bodies. A number of these differences may pose problems as the text mining field moves more into the area of processing full-text articles. However, these differences also present a number of opportunities for the extraction of data types, particularly that found in parenthesized text, that is present in article bodies but not in article abstracts.
We introduce a system developed for the BioCreativeII.5 community evaluation of information extraction of proteins and protein interactions. The paper focuses primarily on the gene normalization task of recognizing protein mentions in text and mapping them to the appropriate database identifiers based on contextual clues. We outline a “fuzzy” dictionary lookup approach to protein mention detection that matches regularized text to similarly-regularized dictionary entries. We describe several different strategies for gene normalization that focus on species or organism mentions in the text, both globally throughout the document and locally in the immediate vicinity of a protein mention, and present the results of experimentation with a series of system variations that explore the effectiveness of the various normalization strategies, as well as the role of external knowledge sources. While our system was neither the best nor the worst performing system in the evaluation, the gene normalization strategies show promise and the system affords the opportunity to explore some of the variables affecting performance on the BCII.5 tasks.
biomedical natural language processing; information extraction; gene normalization; text mining
The Comparative Toxicogenomics Database (CTD) is a publicly available resource that promotes understanding about the etiology of environmental diseases. It provides manually curated chemical-gene/protein interactions and chemical- and gene-disease relationships from the peer-reviewed, published literature. The goals of the research reported here were to establish a baseline analysis of current CTD curation, develop a text-mining prototype from readily available open source components, and evaluate its potential value in augmenting curation efficiency and increasing data coverage.
Prototype text-mining applications were developed and evaluated using a CTD data set consisting of manually curated molecular interactions and relationships from 1,600 documents. Preliminary results indicated that the prototype found 80% of the gene, chemical, and disease terms appearing in curated interactions. These terms were used to re-rank documents for curation, resulting in increases in mean average precision (63% for the baseline vs. 73% for a rule-based re-ranking), and in the correlation coefficient of rank vs. number of curatable interactions per document (baseline 0.14 vs. 0.38 for the rule-based re-ranking).
This text-mining project is unique in its integration of existing tools into a single workflow with direct application to CTD. We performed a baseline assessment of the inter-curator consistency and coverage in CTD, which allowed us to measure the potential of these integrated tools to improve prioritization of journal articles for manual curation. Our study presents a feasible and cost-effective approach for developing a text mining solution to enhance manual curation throughput and efficiency.
Recent years have seen an increased amount of natural language processing (NLP) work on full text biomedical journal publications. Much of this work is done with Open Access journal articles. Such work assumes that Open Access articles are representative of biomedical publications in general and that methods developed for analysis of Open Access full text publications will generalize to the biomedical literature as a whole. If this assumption is wrong, the cost to the community will be large, including not just wasted resources, but also flawed science. This paper examines that assumption.
We collected two sets of documents, one consisting only of Open Access publications and the other consisting only of traditional journal publications. We examined them for differences in surface linguistic structures that have obvious consequences for the ease or difficulty of natural language processing and for differences in semantic content as reflected in lexical items. Regarding surface linguistic structures, we examined the incidence of conjunctions, negation, passives, and pronominal anaphora, and found that the two collections did not differ. We also examined the distribution of sentence lengths and found that both collections were characterized by the same mode. Regarding lexical items, we found that the Kullback-Leibler divergence between the two collections was low, and was lower than the divergence between either collection and a reference corpus. Where small differences did exist, log likelihood analysis showed that they were primarily in the area of formatting and in specific named entities.
We did not find structural or semantic differences between the Open Access and traditional journal collections.
Motivation: It is important for the quality of biological ontologies that similar concepts be expressed consistently, or univocally. Univocality is relevant for the usability of the ontology for humans, as well as for computational tools that rely on regularity in the structure of terms. However, in practice terms are not always expressed consistently, and we must develop methods for identifying terms that are not univocal so that they can be corrected.
Results: We developed an automated transformation-based clustering methodology for detecting terms that use different linguistic conventions for expressing similar semantics. These term sets represent occurrences of univocality violations. Our method was able to identify 67 examples of univocality violations in the Gene Ontology.
Availability: The identified univocality violations are available upon request. We are preparing a release of an open source version of the software to be available at http://bionlp.sourceforge.net.
Summary: Due to the increasing number of text mining resources (tools and corpora) available to biologists, interoperability issues between these resources are becoming significant obstacles to using them effectively. UIMA, the Unstructured Information Management Architecture, is an open framework designed to aid in the construction of more interoperable tools. U-Compare is built on top of the UIMA framework, and provides both a concrete framework for out-of-the-box text mining and a sophisticated evaluation platform allowing users to run specific tools on any target text, generating both detailed statistics and instance-based visualizations of outputs. U-Compare is a joint project, providing the world's largest, and still growing, collection of UIMA-compatible resources. These resources, originally developed by different groups for a variety of domains, include many famous tools and corpora. U-Compare can be launched straight from the web, without needing to be manually installed. All U-Compare components are provided ready-to-use and can be combined easily via a drag-and-drop interface without any programming. External UIMA components can also simply be mixed with U-Compare components, without distinguishing between locally and remotely deployed resources.
A Gene Reference Into Function (GeneRIF) is a concise phrase describing a function of a gene in the Entrez Gene database. Applying techniques from the area of natural language processing known as automatic summarization, it is possible to link the Entrez Gene database, the Gene Ontology, and the biomedical literature. A system was implemented that automatically suggests a sentence from a PubMed/MEDLINE abstract as a candidate GeneRIF by exploiting a gene’s GO annotations along with location features and cue words. Results suggest that the method can significantly increase the number of GeneRIF annotations in Entrez Gene, and that it produces qualitatively more useful GeneRIFs than other methods.
Like the primary scientific literature, GeneRIFs exhibit both growth and obsolescence. NLM’s control over the contents of the Entrez Gene database provides a mechanism for dealing with obsolete data: GeneRIFs are removed from the database when they are found to be of low quality. However, the rapid and extensive growth of Entrez Gene makes manual location of low-quality GeneRIFs problematic. This paper presents a system that takes advantage of the summary-like quality of GeneRIFs to detect low-quality GeneRIFs via a summary revision approach, achieving precision of 89% and recall of 77%. Aspects of the system have been adopted by NLM as a quality assurance mechanism.
This paper presents data on alternations in the argument structure of common domain-specific verbs and their associated verbal nominalizations in the PennBioIE corpus. Alternation is the term in theoretical linguistics for variations in the surface syntactic form of verbs, e.g. the different forms of stimulate in FSH stimulates follicular development and follicular development is stimulated by FSH. The data is used to assess the implications of alternations for biomedical text mining systems and to test the fit of the sublanguage model to biomedical texts.
We examined 1,872 tokens of the ten most common domain-specific verbs or their zero-related nouns in the PennBioIE corpus and labelled them for the presence or absence of three alternations. We then annotated the arguments of 746 tokens of the nominalizations related to these verbs and counted alternations related to the presence or absence of arguments and to the syntactic position of non-absent arguments. We found that alternations are quite common both for verbs and for nominalizations. We also found a previously undescribed alternation involving an adjectival present participle.
We found that even in this semantically restricted domain, alternations are quite common, and alternations involving nominalizations are exceptionally diverse. Nonetheless, the sublanguage model applies to biomedical language. We also report on a previously undescribed alternation involving an adjectival present participle.
Reliable information extraction applications have been a long sought goal of the biomedical text mining community, a goal that if reached would provide valuable tools to benchside biologists in their increasingly difficult task of assimilating the knowledge contained in the biomedical literature. We present an integrated approach to concept recognition in biomedical text. Concept recognition provides key information that has been largely missing from previous biomedical information extraction efforts, namely direct links to well defined knowledge resources that explicitly cement the concept's semantics. The BioCreative II tasks discussed in this special issue have provided a unique opportunity to demonstrate the effectiveness of concept recognition in the field of biomedical language processing.
Through the modular construction of a protein interaction relation extraction system, we present several use cases of concept recognition in biomedical text, and relate these use cases to potential uses by the benchside biologist.
Current information extraction technologies are approaching performance standards at which concept recognition can begin to deliver high quality data to the benchside biologist. Our system is available as part of the BioCreative Meta-Server project and on the internet .
The goal of the gene normalization task is to link genes or gene products mentioned in the literature to biological databases. This is a key step in an accurate search of the biological literature. It is a challenging task, even for the human expert; genes are often described rather than referred to by gene symbol and, confusingly, one gene name may refer to different genes (often from different organisms). For BioCreative II, the task was to list the Entrez Gene identifiers for human genes or gene products mentioned in PubMed/MEDLINE abstracts. We selected abstracts associated with articles previously curated for human genes. We provided 281 expert-annotated abstracts containing 684 gene identifiers for training, and a blind test set of 262 documents containing 785 identifiers, with a gold standard created by expert annotators. Inter-annotator agreement was measured at over 90%.
Twenty groups submitted one to three runs each, for a total of 54 runs. Three systems achieved F-measures (balanced precision and recall) between 0.80 and 0.81. Combining the system outputs using simple voting schemes and classifiers obtained improved results; the best composite system achieved an F-measure of 0.92 with 10-fold cross-validation. A 'maximum recall' system based on the pooled responses of all participants gave a recall of 0.97 (with precision 0.23), identifying 763 out of 785 identifiers.
Major advances for the BioCreative II gene normalization task include broader participation (20 versus 8 teams) and a pooled system performance comparable to human experts, at over 90% agreement. These results show promise as tools to link the literature with biological databases.