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1.  FACTA: a text search engine for finding associated biomedical concepts 
Bioinformatics  2008;24(21):2559-2560.
Summary: FACTA is a text search engine for MEDLINE abstracts, which is designed particularly to help users browse biomedical concepts (e.g. genes/proteins, diseases, enzymes and chemical compounds) appearing in the documents retrieved by the query. The concepts are presented to the user in a tabular format and ranked based on the co-occurrence statistics. Unlike existing systems that provide similar functionality, FACTA pre-indexes not only the words but also the concepts mentioned in the documents, which enables the user to issue a flexible query (e.g. free keywords or Boolean combinations of keywords/concepts) and receive the results immediately even when the number of the documents that match the query is very large. The user can also view snippets from MEDLINE to get textual evidence of associations between the query terms and the concepts. The concept IDs and their names/synonyms for building the indexes were collected from several biomedical databases and thesauri, such as UniProt, BioThesaurus, UMLS, KEGG and DrugBank.
Availability: The system is available at
PMCID: PMC2572701  PMID: 18772154
2.  Disambiguating the species of biomedical named entities using natural language parsers 
Bioinformatics  2010;26(5):661-667.
Motivation: Text mining technologies have been shown to reduce the laborious work involved in organizing the vast amount of information hidden in the literature. One challenge in text mining is linking ambiguous word forms to unambiguous biological concepts. This article reports on a comprehensive study on resolving the ambiguity in mentions of biomedical named entities with respect to model organisms and presents an array of approaches, with focus on methods utilizing natural language parsers.
Results: We build a corpus for organism disambiguation where every occurrence of protein/gene entity is manually tagged with a species ID, and evaluate a number of methods on it. Promising results are obtained by training a machine learning model on syntactic parse trees, which is then used to decide whether an entity belongs to the model organism denoted by a neighbouring species-indicating word (e.g. yeast). The parser-based approaches are also compared with a supervised classification method and results indicate that the former are a more favorable choice when domain portability is of concern. The best overall performance is obtained by combining the strengths of syntactic features and supervised classification.
Availability: The corpus and demo are available at, and the software is freely available as U-Compare components (Kano et al., 2009): NaCTeM Species Word Detector and NaCTeM Species Disambiguator. U-Compare is available at
PMCID: PMC2828111  PMID: 20053840
3.  Text-mining-assisted biocuration workflows in Argo 
Biocuration activities have been broadly categorized into the selection of relevant documents, the annotation of biological concepts of interest and identification of interactions between the concepts. Text mining has been shown to have a potential to significantly reduce the effort of biocurators in all the three activities, and various semi-automatic methodologies have been integrated into curation pipelines to support them. We investigate the suitability of Argo, a workbench for building text-mining solutions with the use of a rich graphical user interface, for the process of biocuration. Central to Argo are customizable workflows that users compose by arranging available elementary analytics to form task-specific processing units. A built-in manual annotation editor is the single most used biocuration tool of the workbench, as it allows users to create annotations directly in text, as well as modify or delete annotations created by automatic processing components. Apart from syntactic and semantic analytics, the ever-growing library of components includes several data readers and consumers that support well-established as well as emerging data interchange formats such as XMI, RDF and BioC, which facilitate the interoperability of Argo with other platforms or resources. To validate the suitability of Argo for curation activities, we participated in the BioCreative IV challenge whose purpose was to evaluate Web-based systems addressing user-defined biocuration tasks. Argo proved to have the edge over other systems in terms of flexibility of defining biocuration tasks. As expected, the versatility of the workbench inevitably lengthened the time the curators spent on learning the system before taking on the task, which may have affected the usability of Argo. The participation in the challenge gave us an opportunity to gather valuable feedback and identify areas of improvement, some of which have already been introduced.
Database URL:
PMCID: PMC4103424  PMID: 25037308
4.  Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases 
PLoS Computational Biology  2010;6(9):e1000943.
The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs.
Author Summary
The biomedical literature is an important source of knowledge on the function of genes and on the mechanisms by which these genes regulate cellular processes. Several text mining approaches have been developed to leverage this rich source of information by automatically extracting associations between concepts such as genes, diseases and drugs from a large body of text. Here, we describe a new method that extracts novel, not yet recognized associations between genes, diseases, drugs and cellular processes from the biomedical literature. Our method is built on the assumption that even if two concepts do not have a direct connection in literature, they may be functionally related if they are both connected to an overlapping set of concepts. Using this approach we predicted several novel connections between genes, diseases, drugs and pathways. Our results imply that our method is able to predict novel relationships from literature and, most importantly, that these newly identified relationships are biologically relevant. Our method can aid the drug discovery process where it can be used to find novel drug targets, increase insight in mode of action of a drug or find novel applications for known drugs.
PMCID: PMC2944780  PMID: 20885778
5.  Argo: an integrative, interactive, text mining-based workbench supporting curation 
Curation of biomedical literature is often supported by the automatic analysis of textual content that generally involves a sequence of individual processing components. Text mining (TM) has been used to enhance the process of manual biocuration, but has been focused on specific databases and tasks rather than an environment integrating TM tools into the curation pipeline, catering for a variety of tasks, types of information and applications. Processing components usually come from different sources and often lack interoperability. The well established Unstructured Information Management Architecture is a framework that addresses interoperability by defining common data structures and interfaces. However, most of the efforts are targeted towards software developers and are not suitable for curators, or are otherwise inconvenient to use on a higher level of abstraction. To overcome these issues we introduce Argo, an interoperable, integrative, interactive and collaborative system for text analysis with a convenient graphic user interface to ease the development of processing workflows and boost productivity in labour-intensive manual curation. Robust, scalable text analytics follow a modular approach, adopting component modules for distinct levels of text analysis. The user interface is available entirely through a web browser that saves the user from going through often complicated and platform-dependent installation procedures. Argo comes with a predefined set of processing components commonly used in text analysis, while giving the users the ability to deposit their own components. The system accommodates various areas and levels of user expertise, from TM and computational linguistics to ontology-based curation. One of the key functionalities of Argo is its ability to seamlessly incorporate user-interactive components, such as manual annotation editors, into otherwise completely automatic pipelines. As a use case, we demonstrate the functionality of an in-built manual annotation editor that is well suited for in-text corpus annotation tasks.
Database URL:
PMCID: PMC3308166  PMID: 22434844
6.  Dragon exploration system on marine sponge compounds interactions 
Natural products are considered a rich source of new chemical structures that may lead to the therapeutic agents in all major disease areas. About 50% of the drugs introduced in the market in the last 20 years were natural products/derivatives or natural products mimics, which clearly shows the influence of natural products in drug discovery.
In an effort to further support the research in this field, we have developed an integrative knowledge base on Marine Sponge Compounds Interactions (Dragon Exploration System on Marine Sponge Compounds Interactions - DESMSCI) as a web resource. This knowledge base provides information about the associations of the sponge compounds with different biological concepts such as human genes or proteins, diseases, as well as pathways, based on the literature information available in PubMed and information deposited in several other databases. As such, DESMSCI is aimed as a research support resource for problems on the utilization of marine sponge compounds. DESMSCI allows visualization of relationships between different chemical compounds and biological concepts through textual and tabular views, graphs and relational networks. In addition, DESMSCI has built in hypotheses discovery module that generates potentially new/interesting associations among different biomedical concepts. We also present a case study derived from the hypotheses generated by DESMSCI which provides a possible novel mode of action for variolins in Alzheimer’s disease.
DESMSCI is the first publicly available ( comprehensive resource where users can explore information, compiled by text- and data-mining approaches, on biological and chemical data related to sponge compounds.
PMCID: PMC3608955  PMID: 23415072
Sponge compounds interactions; Natural products; Text-mining; Information integration; Knowledge base
7.  AGRA: analysis of gene ranking algorithms 
Bioinformatics  2011;27(8):1185-1186.
Summary: Often, the most informative genes have to be selected from different gene sets and several computer gene ranking algorithms have been developed to cope with the problem. To help researchers decide which algorithm to use, we developed the analysis of gene ranking algorithms (AGRA) system that offers a novel technique for comparing ranked lists of genes. The most important feature of AGRA is that no previous knowledge of gene ranking algorithms is needed for their comparison. Using the text mining system finding-associated concepts with text analysis. AGRA defines what we call biomedical concept space (BCS) for each gene list and offers a comparison of the gene lists in six different BCS categories. The uploaded gene lists can be compared using two different methods. In the first method, the overlap between each pair of two gene lists of BCSs is calculated. The second method offers a text field where a specific biomedical concept can be entered. AGRA searches for this concept in each gene lists' BCS, highlights the rank of the concept and offers a visual representation of concepts ranked above and below it.
Availability and Implementation: Available at, implemented in Java and running on the Glassfish server.
PMCID: PMC3072556  PMID: 21349873
8.  An open annotation ontology for science on web 3.0 
Journal of Biomedical Semantics  2011;2(Suppl 2):S4.
There is currently a gap between the rich and expressive collection of published biomedical ontologies, and the natural language expression of biomedical papers consumed on a daily basis by scientific researchers. The purpose of this paper is to provide an open, shareable structure for dynamic integration of biomedical domain ontologies with the scientific document, in the form of an Annotation Ontology (AO), thus closing this gap and enabling application of formal biomedical ontologies directly to the literature as it emerges.
Initial requirements for AO were elicited by analysis of integration needs between biomedical web communities, and of needs for representing and integrating results of biomedical text mining. Analysis of strengths and weaknesses of previous efforts in this area was also performed. A series of increasingly refined annotation tools were then developed along with a metadata model in OWL, and deployed for feedback and additional requirements the ontology to users at a major pharmaceutical company and a major academic center. Further requirements and critiques of the model were also elicited through discussions with many colleagues and incorporated into the work.
This paper presents Annotation Ontology (AO), an open ontology in OWL-DL for annotating scientific documents on the web. AO supports both human and algorithmic content annotation. It enables “stand-off” or independent metadata anchored to specific positions in a web document by any one of several methods. In AO, the document may be annotated but is not required to be under update control of the annotator. AO contains a provenance model to support versioning, and a set model for specifying groups and containers of annotation. AO is freely available under open source license at, and extensive documentation including screencasts is available on AO’s Google Code page: .
The Annotation Ontology meets critical requirements for an open, freely shareable model in OWL, of annotation metadata created against scientific documents on the Web. We believe AO can become a very useful common model for annotation metadata on Web documents, and will enable biomedical domain ontologies to be used quite widely to annotate the scientific literature. Potential collaborators and those with new relevant use cases are invited to contact the authors.
PMCID: PMC3102893  PMID: 21624159
9.  Concept annotation in the CRAFT corpus 
BMC Bioinformatics  2012;13:161.
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
PMCID: PMC3476437  PMID: 22776079
10.  LiverCancerMarkerRIF: a liver cancer biomarker interactive curation system combining text mining and expert annotations 
Biomarkers are biomolecules in the human body that can indicate disease states and abnormal biological processes. Biomarkers are often used during clinical trials to identify patients with cancers. Although biomedical research related to biomarkers has increased over the years and substantial effort has been expended to obtain results in these studies, the specific results obtained often contain ambiguities, and the results might contradict each other. Therefore, the information gathered from these studies must be appropriately integrated and organized to facilitate experimentation on biomarkers. In this study, we used liver cancer as the target and developed a text-mining–based curation system named LiverCancerMarkerRIF, which allows users to retrieve biomarker-related narrations and curators to curate supporting evidence on liver cancer biomarkers directly while browsing PubMed. In contrast to most of the other curation tools that require curators to navigate away from PubMed and accommodate distinct user interfaces or Web sites to complete the curation process, our system provides a user-friendly method for accessing text-mining–aided information and a concise interface to assist curators while they remain at the PubMed Web site. Biomedical text-mining techniques are applied to automatically recognize biomedical concepts such as genes, microRNA, diseases and investigative technologies, which can be used to evaluate the potential of a certain gene as a biomarker. Through the participation in the BioCreative IV user-interactive task, we examined the feasibility of using this novel type of augmented browsing-based curation method, and collaborated with curators to curate biomarker evidential sentences related to liver cancer. The positive feedback received from curators indicates that the proposed method can be effectively used for curation. A publicly available online database containing all the aforementioned information has been constructed at in an attempt to facilitate biomarker-related studies.
Database URL:
PMCID: PMC4147259  PMID: 25168057
11.  Large-Scale Event Extraction from Literature with Multi-Level Gene Normalization 
PLoS ONE  2013;8(4):e55814.
Text mining for the life sciences aims to aid database curation, knowledge summarization and information retrieval through the automated processing of biomedical texts. To provide comprehensive coverage and enable full integration with existing biomolecular database records, it is crucial that text mining tools scale up to millions of articles and that their analyses can be unambiguously linked to information recorded in resources such as UniProt, KEGG, BioGRID and NCBI databases. In this study, we investigate how fully automated text mining of complex biomolecular events can be augmented with a normalization strategy that identifies biological concepts in text, mapping them to identifiers at varying levels of granularity, ranging from canonicalized symbols to unique gene and proteins and broad gene families. To this end, we have combined two state-of-the-art text mining components, previously evaluated on two community-wide challenges, and have extended and improved upon these methods by exploiting their complementary nature. Using these systems, we perform normalization and event extraction to create a large-scale resource that is publicly available, unique in semantic scope, and covers all 21.9 million PubMed abstracts and 460 thousand PubMed Central open access full-text articles. This dataset contains 40 million biomolecular events involving 76 million gene/protein mentions, linked to 122 thousand distinct genes from 5032 species across the full taxonomic tree. Detailed evaluations and analyses reveal promising results for application of this data in database and pathway curation efforts. The main software components used in this study are released under an open-source license. Further, the resulting dataset is freely accessible through a novel API, providing programmatic and customized access ( Finally, to allow for large-scale bioinformatic analyses, the entire resource is available for bulk download from, under the Creative Commons – Attribution – Share Alike (CC BY-SA) license.
PMCID: PMC3629104  PMID: 23613707
12.  Processing biological literature with customizable Web services supporting interoperable formats 
Web services have become a popular means of interconnecting solutions for processing a body of scientific literature. This has fuelled research on high-level data exchange formats suitable for a given domain and ensuring the interoperability of Web services. In this article, we focus on the biological domain and consider four interoperability formats, BioC, BioNLP, XMI and RDF, that represent domain-specific and generic representations and include well-established as well as emerging specifications. We use the formats in the context of customizable Web services created in our Web-based, text-mining workbench Argo that features an ever-growing library of elementary analytics and capabilities to build and deploy Web services straight from a convenient graphical user interface. We demonstrate a 2-fold customization of Web services: by building task-specific processing pipelines from a repository of available analytics, and by configuring services to accept and produce a combination of input and output data interchange formats. We provide qualitative evaluation of the formats as well as quantitative evaluation of automatic analytics. The latter was carried out as part of our participation in the fourth edition of the BioCreative challenge. Our analytics built into Web services for recognizing biochemical concepts in BioC collections achieved the highest combined scores out of 10 participating teams.
Database URL:
PMCID: PMC4086403  PMID: 25006225
13.  The Protein-Protein Interaction tasks of BioCreative III: classification/ranking of articles and linking bio-ontology concepts to full text 
BMC Bioinformatics  2011;12(Suppl 8):S3.
Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them.
A total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35%) the macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of 55%.
The results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heterogeneity and different granularity of method term concepts encountered in the ontology. However, combining the sophisticated techniques developed by the participants with supporting evidence strings derived from the articles for human interpretation could result in practical modules for biological annotation workflows.
PMCID: PMC3269938  PMID: 22151929
Natural language processing (NLP) is a high throughput technology because it can process vast quantities of text within a reasonable time period. It has the potential to substantially facilitate biomedical research by extracting, linking, and organizing massive amounts of information that occur in biomedical journal articles as well as in textual fields of biological databases. Until recently, much of the work in biological NLP and text mining has revolved around recognizing the occurrence of biomolecular entities in articles, and in extracting particular relationships among the entities. Now, researchers have recognized a need to link the extracted information to ontologies or knowledge bases, which is a more difficult task. One such knowledge base is Gene Ontology annotations (GOA), which significantly increases semantic computations over the function, cellular components and processes of genes. For multicellular organisms, these annotations can be refined with phenotypic context, such as the cell type, tissue, and organ because establishing phenotypic contexts in which a gene is expressed is a crucial step for understanding the development and the molecular underpinning of the pathophysiology of diseases. In this paper, we propose a system, PhenoGO, which automatically augments annotations in GOA with additional context. PhenoGO utilizes an existing NLP system, called BioMedLEE, an existing knowledge-based phenotype organizer system (PhenOS) in conjunction with MeSH indexing and established biomedical ontologies. More specifically, PhenoGO adds phenotypic contextual information to existing associations between gene products and GO terms as specified in GOA. The system also maps the context to identifiers that are associated with different biomedical ontologies, including the UMLS, Cell Ontology, Mouse Anatomy, NCBI taxonomy, GO, and Mammalian Phenotype Ontology. In addition, PhenoGO was evaluated for coding of anatomical and cellular information and assigning the coded phenotypes to the correct GOA; results obtained show that PhenoGO has a precision of 91% and recall of 92%, demonstrating that the PhenoGO NLP system can accurately encode a large number of anatomical and cellular ontologies to GO annotations. The PhenoGO Database may be accessed at the following URL:
PMCID: PMC2906243  PMID: 17094228
15.  PosMed: ranking genes and bioresources based on Semantic Web Association Study 
Nucleic Acids Research  2013;41(Web Server issue):W109-W114.
Positional MEDLINE (PosMed; is a powerful Semantic Web Association Study engine that ranks biomedical resources such as genes, metabolites, diseases and drugs, based on the statistical significance of associations between user-specified phenotypic keywords and resources connected directly or inferentially through a Semantic Web of biological databases such as MEDLINE, OMIM, pathways, co-expressions, molecular interactions and ontology terms. Since 2005, PosMed has long been used for in silico positional cloning studies to infer candidate disease-responsible genes existing within chromosomal intervals. PosMed is redesigned as a workbench to discover possible functional interpretations for numerous genetic variants found from exome sequencing of human disease samples. We also show that the association search engine enhances the value of mouse bioresources because most knockout mouse resources have no phenotypic annotation, but can be associated inferentially to phenotypes via genes and biomedical documents. For this purpose, we established text-mining rules to the biomedical documents by careful human curation work, and created a huge amount of correct linking between genes and documents. PosMed associates any phenotypic keyword to mouse resources with 20 public databases and four original data sets as of May 2013.
PMCID: PMC3692089  PMID: 23761449
16.  User centered and ontology based information retrieval system for life sciences 
BMC Bioinformatics  2012;13(Suppl 1):S4.
Because of the increasing number of electronic resources, designing efficient tools to retrieve and exploit them is a major challenge. Some improvements have been offered by semantic Web technologies and applications based on domain ontologies. In life science, for instance, the Gene Ontology is widely exploited in genomic applications and the Medical Subject Headings is the basis of biomedical publications indexation and information retrieval process proposed by PubMed. However current search engines suffer from two main drawbacks: there is limited user interaction with the list of retrieved resources and no explanation for their adequacy to the query is provided. Users may thus be confused by the selection and have no idea on how to adapt their queries so that the results match their expectations.
This paper describes an information retrieval system that relies on domain ontology to widen the set of relevant documents that is retrieved and that uses a graphical rendering of query results to favor user interactions. Semantic proximities between ontology concepts and aggregating models are used to assess documents adequacy with respect to a query. The selection of documents is displayed in a semantic map to provide graphical indications that make explicit to what extent they match the user's query; this man/machine interface favors a more interactive and iterative exploration of data corpus, by facilitating query concepts weighting and visual explanation. We illustrate the benefit of using this information retrieval system on two case studies one of which aiming at collecting human genes related to transcription factors involved in hemopoiesis pathway.
The ontology based information retrieval system described in this paper (OBIRS) is freely available at: This environment is a first step towards a user centred application in which the system enlightens relevant information to provide decision help.
PMCID: PMC3434427  PMID: 22373375
17.  Alkemio: association of chemicals with biomedical topics by text and data mining 
Nucleic Acids Research  2014;42(Web Server issue):W422-W429.
The PubMed® database of biomedical citations allows the retrieval of scientific articles studying the function of chemicals in biology and medicine. Mining millions of available citations to search reported associations between chemicals and topics of interest would require substantial human time. We have implemented the Alkemio text mining web tool and SOAP web service to help in this task. The tool uses biomedical articles discussing chemicals (including drugs), predicts their relatedness to the query topic with a naïve Bayesian classifier and ranks all chemicals by P-values computed from random simulations. Benchmarks on seven human pathways showed good retrieval performance (areas under the receiver operating characteristic curves ranged from 73.6 to 94.5%). Comparison with existing tools to retrieve chemicals associated to eight diseases showed the higher precision and recall of Alkemio when considering the top 10 candidate chemicals. Alkemio is a high performing web tool ranking chemicals for any biomedical topics and it is free to non-commercial users. Availability:∼medlineranker/cms/alkemio.
PMCID: PMC4086102  PMID: 24838570
18.  PathBinder – text empirics and automatic extraction of biomolecular interactions 
BMC Bioinformatics  2009;10(Suppl 11):S18.
The increasingly large amount of free, online biological text makes automatic interaction extraction correspondingly attractive. Machine learning is one strategy that works by uncovering and using useful properties that are implicit in the text. However these properties are usually not reported in the literature explicitly. By investigating specific properties of biological text passages in this paper, we aim to facilitate an alternative strategy, the use of text empirics, to support mining of biomedical texts for biomolecular interactions. We report on our application of this approach, and also report some empirical findings about an important class of passages. These may be useful to others who may also wish to use the empirical properties we describe.
We manually analyzed syntactic and semantic properties of sentences likely to describe interactions between biomolecules. The resulting empirical data were used to design an algorithm for the PathBinder system to extract biomolecular interactions from texts. PathBinder searches PubMed for sentences describing interactions between two given biomolecules. PathBinder then uses probabilistic methods to combine evidence from multiple relevant sentences in PubMed to assess the relative likelihood of interaction between two arbitrary biomolecules. A biomolecular interaction network was constructed based on those likelihoods.
The text empirics approach used here supports computationally friendly, performance competitive, automatic extraction of biomolecular interactions from texts.
PMCID: PMC3226189  PMID: 19811683
19.  Are figure legends sufficient? Evaluating the contribution of associated text to biomedical figure comprehension 
Biomedical scientists need to access figures to validate research facts and to formulate or to test novel research hypotheses. However, figures are difficult to comprehend without associated text (e.g., figure legend and other reference text). We are developing automated systems to extract the relevant explanatory information along with figures extracted from full text articles. Such systems could be very useful in improving figure retrieval and in reducing the workload of biomedical scientists, who otherwise have to retrieve and read the entire full-text journal article to determine which figures are relevant to their research. As a crucial step, we studied the importance of associated text in biomedical figure comprehension.
Twenty subjects evaluated three figure-text combinations: figure+legend, figure+legend+title+abstract, and figure+full-text. Using a Likert scale, each subject scored each figure+text according to the extent to which the subject thought he/she understood the meaning of the figure and the confidence in providing the assigned score. Additionally, each subject entered a free text summary for each figure-text. We identified missing information using indicator words present within the text summaries. Both the Likert scores and the missing information were statistically analyzed for differences among the figure-text types. We also evaluated the quality of text summaries with the text-summarization evaluation method the ROUGE score.
Our results showed statistically significant differences in figure comprehension when varying levels of text were provided. When the full-text article is not available, presenting just the figure+legend left biomedical researchers lacking 39–68% of the information about a figure as compared to having complete figure comprehension; adding the title and abstract improved the situation, but still left biomedical researchers missing 30% of the information. When the full-text article is available, figure comprehension increased to 86–97%; this indicates that researchers felt that only 3–14% of the necessary information for full figure comprehension was missing when full text was available to them. Clearly there is information in the abstract and in the full text that biomedical scientists deem important for understanding the figures that appear in full-text biomedical articles.
We conclude that the texts that appear in full-text biomedical articles are useful for understanding the meaning of a figure, and an effective figure-mining system needs to unlock the information beyond figure legend. Our work provides important guidance to the figure mining systems that extract information only from figure and figure legend.
PMCID: PMC2631451  PMID: 19126221
20.  Integration and publication of heterogeneous text-mined relationships on the Semantic Web 
Journal of Biomedical Semantics  2011;2(Suppl 2):S10.
Advances in Natural Language Processing (NLP) techniques enable the extraction of fine-grained relationships mentioned in biomedical text. The variability and the complexity of natural language in expressing similar relationships causes the extracted relationships to be highly heterogeneous, which makes the construction of knowledge bases difficult and poses a challenge in using these for data mining or question answering.
We report on the semi-automatic construction of the PHARE relationship ontology (the PHArmacogenomic RElationships Ontology) consisting of 200 curated relations from over 40,000 heterogeneous relationships extracted via text-mining. These heterogeneous relations are then mapped to the PHARE ontology using synonyms, entity descriptions and hierarchies of entities and roles. Once mapped, relationships can be normalized and compared using the structure of the ontology to identify relationships that have similar semantics but different syntax. We compare and contrast the manual procedure with a fully automated approach using WordNet to quantify the degree of integration enabled by iterative curation and refinement of the PHARE ontology. The result of such integration is a repository of normalized biomedical relationships, named PHARE-KB, which can be queried using Semantic Web technologies such as SPARQL and can be visualized in the form of a biological network.
The PHARE ontology serves as a common semantic framework to integrate more than 40,000 relationships pertinent to pharmacogenomics. The PHARE ontology forms the foundation of a knowledge base named PHARE-KB. Once populated with relationships, PHARE-KB (i) can be visualized in the form of a biological network to guide human tasks such as database curation and (ii) can be queried programmatically to guide bioinformatics applications such as the prediction of molecular interactions. PHARE is available at
PMCID: PMC3102890  PMID: 21624156
21.  Rewriting and suppressing UMLS terms for improved biomedical term identification 
Identification of terms is essential for biomedical text mining.. We concentrate here on the use of vocabularies for term identification, specifically the Unified Medical Language System (UMLS). To make the UMLS more suitable for biomedical text mining we implemented and evaluated nine term rewrite and eight term suppression rules. The rules rely on UMLS properties that have been identified in previous work by others, together with an additional set of new properties discovered by our group during our work with the UMLS. Our work complements the earlier work in that we measure the impact on the number of terms identified by the different rules on a MEDLINE corpus. The number of uniquely identified terms and their frequency in MEDLINE were computed before and after applying the rules. The 50 most frequently found terms together with a sample of 100 randomly selected terms were evaluated for every rule.
Five of the nine rewrite rules were found to generate additional synonyms and spelling variants that correctly corresponded to the meaning of the original terms and seven out of the eight suppression rules were found to suppress only undesired terms. Using the five rewrite rules that passed our evaluation, we were able to identify 1,117,772 new occurrences of 14,784 rewritten terms in MEDLINE. Without the rewriting, we recognized 651,268 terms belonging to 397,414 concepts; with rewriting, we recognized 666,053 terms belonging to 410,823 concepts, which is an increase of 2.8% in the number of terms and an increase of 3.4% in the number of concepts recognized. Using the seven suppression rules, a total of 257,118 undesired terms were suppressed in the UMLS, notably decreasing its size. 7,397 terms were suppressed in the corpus.
We recommend applying the five rewrite rules and seven suppression rules that passed our evaluation when the UMLS is to be used for biomedical term identification in MEDLINE. A software tool to apply these rules to the UMLS is freely available at
PMCID: PMC2895736  PMID: 20618981
22.  Pharmspresso: a text mining tool for extraction of pharmacogenomic concepts and relationships from full text 
BMC Bioinformatics  2009;10(Suppl 2):S6.
Pharmacogenomics studies the relationship between genetic variation and the variation in drug response phenotypes. The field is rapidly gaining importance: it promises drugs targeted to particular subpopulations based on genetic background. The pharmacogenomics literature has expanded rapidly, but is dispersed in many journals. It is challenging, therefore, to identify important associations between drugs and molecular entities – particularly genes and gene variants, and thus these critical connections are often lost. Text mining techniques can allow us to convert the free-style text to a computable, searchable format in which pharmacogenomic concepts (such as genes, drugs, polymorphisms, and diseases) are identified, and important links between these concepts are recorded. Availability of full text articles as input into text mining engines is key, as literature abstracts often do not contain sufficient information to identify these pharmacogenomic associations.
Thus, building on a tool called Textpresso, we have created the Pharmspresso tool to assist in identifying important pharmacogenomic facts in full text articles. Pharmspresso parses text to find references to human genes, polymorphisms, drugs and diseases and their relationships. It presents these as a series of marked-up text fragments, in which key concepts are visually highlighted. To evaluate Pharmspresso, we used a gold standard of 45 human-curated articles. Pharmspresso identified 78%, 61%, and 74% of target gene, polymorphism, and drug concepts, respectively.
Pharmspresso is a text analysis tool that extracts pharmacogenomic concepts from the literature automatically and thus captures our current understanding of gene-drug interactions in a computable form. We have made Pharmspresso available at .
PMCID: PMC2646239  PMID: 19208194
23.  Combining Position Weight Matrices and Document-Term Matrix for Efficient Extraction of Associations of Methylated Genes and Diseases from Free Text 
PLoS ONE  2013;8(10):e77848.
In a number of diseases, certain genes are reported to be strongly methylated and thus can serve as diagnostic markers in many cases. Scientific literature in digital form is an important source of information about methylated genes implicated in particular diseases. The large volume of the electronic text makes it difficult and impractical to search for this information manually.
We developed a novel text mining methodology based on a new concept of position weight matrices (PWMs) for text representation and feature generation. We applied PWMs in conjunction with the document-term matrix to extract with high accuracy associations between methylated genes and diseases from free text. The performance results are based on large manually-classified data. Additionally, we developed a web-tool, DEMGD, which automates extraction of these associations from free text. DEMGD presents the extracted associations in summary tables and full reports in addition to evidence tagging of text with respect to genes, diseases and methylation words. The methodology we developed in this study can be applied to similar association extraction problems from free text.
The new methodology developed in this study allows for efficient identification of associations between concepts. Our method applied to methylated genes in different diseases is implemented as a Web-tool, DEMGD, which is freely available at The data is available for online browsing and download.
PMCID: PMC3797705  PMID: 24147091
24.  Information Exploration System for Sickle Cell Disease and Repurposing of Hydroxyfasudil 
PLoS ONE  2013;8(6):e65190.
Sickle cell disease (SCD) is a fatal monogenic disorder with no effective cure and thus high rates of morbidity and sequelae. Efforts toward discovery of disease modifying drugs and curative strategies can be augmented by leveraging the plethora of information contained in available biomedical literature. To facilitate research in this direction we have developed a resource, Dragon Exploration System for Sickle Cell Disease (DESSCD) ( that aims to promote the easy exploration of SCD-related data.
The Dragon Exploration System (DES), developed based on text mining and complemented by data mining, processed 419,612 MEDLINE abstracts retrieved from a PubMed query using SCD-related keywords. The processed SCD-related data has been made available via the DESSCD web query interface that enables: a/information retrieval using specified concepts, keywords and phrases, and b/the generation of inferred association networks and hypotheses. The usefulness of the system is demonstrated by: a/reproducing a known scientific fact, the “Sickle_Cell_Anemia–Hydroxyurea” association, and b/generating novel and plausible “Sickle_Cell_Anemia–Hydroxyfasudil” hypothesis. A PCT patent (PCT/US12/55042) has been filed for the latter drug repurposing for SCD treatment.
We developed the DESSCD resource dedicated to exploration of text-mined and data-mined information about SCD. No similar SCD-related resource exists. Thus, we anticipate that DESSCD will serve as a valuable tool for physicians and researchers interested in SCD.
PMCID: PMC3677893  PMID: 23762313
25.  Detecting causality from online psychiatric texts using inter-sentential language patterns 
Online psychiatric texts are natural language texts expressing depressive problems, published by Internet users via community-based web services such as web forums, message boards and blogs. Understanding the cause-effect relations embedded in these psychiatric texts can provide insight into the authors’ problems, thus increasing the effectiveness of online psychiatric services.
Previous studies have proposed the use of word pairs extracted from a set of sentence pairs to identify cause-effect relations between sentences. A word pair is made up of two words, with one coming from the cause text span and the other from the effect text span. Analysis of the relationship between these words can be used to capture individual word associations between cause and effect sentences. For instance, (broke up, life) and (boyfriend, meaningless) are two word pairs extracted from the sentence pair: “I broke up with my boyfriend. Life is now meaningless to me”. The major limitation of word pairs is that individual words in sentences usually cannot reflect the exact meaning of the cause and effect events, and thus may produce semantically incomplete word pairs, as the previous examples show. Therefore, this study proposes the use of inter-sentential language patterns such as ≪broke up, boyfriend>,
Performance was evaluated on a corpus of texts collected from PsychPark (, a virtual psychiatric clinic maintained by a group of volunteer professionals from the Taiwan Association of Mental Health Informatics. Experimental results show that the use of inter-sentential language patterns outperformed the use of word pairs proposed in previous studies.
This study demonstrates the acquisition of inter-sentential language patterns for causality detection from online psychiatric texts. Such semantically more complete and precise features can improve causality detection performance.
PMCID: PMC3441867  PMID: 22809317
Causality detection; Inter-sentential language patterns; Biomedical text mining; Natural language processing

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