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1.  Discovering and visualizing indirect associations between biomedical concepts 
Bioinformatics  2011;27(13):i111-i119.
Motivation: Discovering useful associations between biomedical concepts has been one of the main goals in biomedical text-mining, and understanding their biomedical contexts is crucial in the discovery process. Hence, we need a text-mining system that helps users explore various types of (possibly hidden) associations in an easy and comprehensible manner.
Results: This article describes FACTA+, a real-time text-mining system for finding and visualizing indirect associations between biomedical concepts from MEDLINE abstracts. The system can be used as a text search engine like PubMed with additional features to help users discover and visualize indirect associations between important biomedical concepts such as genes, diseases and chemical compounds. FACTA+ inherits all functionality from its predecessor, FACTA, and extends it by incorporating three new features: (i) detecting biomolecular events in text using a machine learning model, (ii) discovering hidden associations using co-occurrence statistics between concepts, and (iii) visualizing associations to improve the interpretability of the output. To the best of our knowledge, FACTA+ is the first real-time web application that offers the functionality of finding concepts involving biomolecular events and visualizing indirect associations of concepts with both their categories and importance.
Availability: FACTA+ is available as a web application at, and its visualizer is available at
PMCID: PMC3117364  PMID: 21685059
2.  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
3.  Integration of metabolic databases for the reconstruction of genome-scale metabolic networks 
BMC Systems Biology  2010;4:114.
Genome-scale metabolic reconstructions have been recognised as a valuable tool for a variety of applications ranging from metabolic engineering to evolutionary studies. However, the reconstruction of such networks remains an arduous process requiring a high level of human intervention. This process is further complicated by occurrences of missing or conflicting information and the absence of common annotation standards between different data sources.
In this article, we report a semi-automated methodology aimed at streamlining the process of metabolic network reconstruction by enabling the integration of different genome-wide databases of metabolic reactions. We present results obtained by applying this methodology to the metabolic network of the plant Arabidopsis thaliana. A systematic comparison of compounds and reactions between two genome-wide databases allowed us to obtain a high-quality core consensus reconstruction, which was validated for stoichiometric consistency. A lower level of consensus led to a larger reconstruction, which has a lower quality standard but provides a baseline for further manual curation.
This semi-automated methodology may be applied to other organisms and help to streamline the process of genome-scale network reconstruction in order to accelerate the transfer of such models to applications.
PMCID: PMC2930596  PMID: 20712863
4.  PathText: a text mining integrator for biological pathway visualizations 
Bioinformatics  2010;26(12):i374-i381.
Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations.
PMCID: PMC2881405  PMID: 20529930
5.  Accelerating the annotation of sparse named entities by dynamic sentence selection 
BMC Bioinformatics  2008;9(Suppl 11):S8.
Previous studies of named entity recognition have shown that a reasonable level of recognition accuracy can be achieved by using machine learning models such as conditional random fields or support vector machines. However, the lack of training data (i.e. annotated corpora) makes it difficult for machine learning-based named entity recognizers to be used in building practical information extraction systems.
This paper presents an active learning-like framework for reducing the human effort required to create named entity annotations in a corpus. In this framework, the annotation work is performed as an iterative and interactive process between the human annotator and a probabilistic named entity tagger. Unlike active learning, our framework aims to annotate all occurrences of the target named entities in the given corpus, so that the resulting annotations are free from the sampling bias which is inevitable in active learning approaches.
We evaluate our framework by simulating the annotation process using two named entity corpora and show that our approach can reduce the number of sentences which need to be examined by the human annotator. The cost reduction achieved by the framework could be drastic when the target named entities are sparse.
PMCID: PMC2586757  PMID: 19025694
6.  How to make the most of NE dictionaries in statistical NER 
BMC Bioinformatics  2008;9(Suppl 11):S5.
When term ambiguity and variability are very high, dictionary-based Named Entity Recognition (NER) is not an ideal solution even though large-scale terminological resources are available. Many researches on statistical NER have tried to cope with these problems. However, it is not straightforward how to exploit existing and additional Named Entity (NE) dictionaries in statistical NER. Presumably, addition of NEs to an NE dictionary leads to better performance. However, in reality, the retraining of NER models is required to achieve this. We chose protein name recognition as a case study because it most suffers the problems related to heavy term variation and ambiguity.
We have established a novel way to improve the NER performance by adding NEs to an NE dictionary without retraining. In our approach, first, known NEs are identified in parallel with Part-of-Speech (POS) tagging based on a general word dictionary and an NE dictionary. Then, statistical NER is trained on the POS/PROTEIN tagger outputs with correct NE labels attached.
We evaluated performance of our NER on the standard JNLPBA-2004 data set. The F-score on the test set has been improved from 73.14 to 73.78 after adding protein names appearing in the training data to the POS tagger dictionary without any model retraining. The performance further increased to 78.72 after enriching the tagging dictionary with test set protein names.
Our approach has demonstrated high performance in protein name recognition, which indicates how to make the most of known NEs in statistical NER.
PMCID: PMC2586754  PMID: 19025691
7.  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
8.  Normalizing biomedical terms by minimizing ambiguity and variability 
BMC Bioinformatics  2008;9(Suppl 3):S2.
One of the difficulties in mapping biomedical named entities, e.g. genes, proteins, chemicals and diseases, to their concept identifiers stems from the potential variability of the terms. Soft string matching is a possible solution to the problem, but its inherent heavy computational cost discourages its use when the dictionaries are large or when real time processing is required. A less computationally demanding approach is to normalize the terms by using heuristic rules, which enables us to look up a dictionary in a constant time regardless of its size. The development of good heuristic rules, however, requires extensive knowledge of the terminology in question and thus is the bottleneck of the normalization approach.
We present a novel framework for discovering a list of normalization rules from a dictionary in a fully automated manner. The rules are discovered in such a way that they minimize the ambiguity and variability of the terms in the dictionary. We evaluated our algorithm using two large dictionaries: a human gene/protein name dictionary built from BioThesaurus and a disease name dictionary built from UMLS.
The experimental results showed that automatically discovered rules can perform comparably to carefully crafted heuristic rules in term mapping tasks, and the computational overhead of rule application is small enough that a very fast implementation is possible. This work will help improve the performance of term-concept mapping tasks in biomedical information extraction especially when good normalization heuristics for the target terminology are not fully known.
PMCID: PMC2352870  PMID: 18426547
9.  Automatic recognition of topic-classified relations between prostate cancer and genes using MEDLINE abstracts 
BMC Bioinformatics  2006;7(Suppl 3):S4.
Automatic recognition of relations between a specific disease term and its relevant genes or protein terms is an important practice of bioinformatics. Considering the utility of the results of this approach, we identified prostate cancer and gene terms with the ID tags of public biomedical databases. Moreover, considering that genetics experts will use our results, we classified them based on six topics that can be used to analyze the type of prostate cancers, genes, and their relations.
We developed a maximum entropy-based named entity recognizer and a relation recognizer and applied them to a corpus-based approach. We collected prostate cancer-related abstracts from MEDLINE, and constructed an annotated corpus of gene and prostate cancer relations based on six topics by biologists. We used it to train the maximum entropy-based named entity recognizer and relation recognizer.
Topic-classified relation recognition achieved 92.1% precision for the relation (an increase of 11.0% from that obtained in a baseline experiment). For all topics, the precision was between 67.6 and 88.1%.
A series of experimental results revealed two important findings: a carefully designed relation recognition system using named entity recognition can improve the performance of relation recognition, and topic-classified relation recognition can be effectively addressed through a corpus-based approach using manual annotation and machine learning techniques.
PMCID: PMC1764448  PMID: 17134477

Results 1-9 (9)