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Automatic extension of Gene Ontology with flexible identification of candidate terms.

MOTIVATION: Gene Ontology (GO) has been manually developed to provide a controlled vocabulary for gene product attributes. It continues to evolve with new concepts that are compiled mostly from existing concepts in a compositional way. If we consider the relatively slow growth rate of GO in the face of the fast accumulation of the biological data, it is much desirable to provide an automatic means for predicting new concepts from the existing ones. RESULTS: We present a novel method that predicts more detailed concepts by utilizing syntactic relations among the existing concepts. We propose a validation measure for the automatically predicted concepts by matching the concepts to biomedical articles. We also suggest how to find a suitable direction for the extension of a constantly growing ontology such as GO. AVAILABILITY: http://autogo.biopathway.org SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Algorithms↗

siRecords: an extensive database of mammalian siRNAs with efficacy ratings.

UNLABELLED: Short interfering RNAs (siRNAs) have been gaining popularity as the gene knock-down tool of choice by many researchers because of the clean nature of their workings as well as the technical simplicity and cost efficiency in their applications. We have constructed siRecords, a database of siRNAs experimentally tested by researchers with consistent efficacy ratings. This database will help siRNA researchers develop more reliable siRNA design rules; in the mean time, siRecords will benefit experimental researchers directly by providing them with information about the siRNAs that have been experimentally tested against the genes of their interest. Currently, more than 4100 carefully annotated siRNA sequences obtained from more than 1200 published siRNA studies are hosted in siRecords. This database will continue to expand as more experimentally tested siRNAs are published. AVAILABILITY: The siRecords database can be accessed at http://siRecords.umn.edu/siRecords/

Abstracting and Indexing↗

Functional bioinformatics for Arabidopsis thaliana.

MOTIVATION: The genome of Arabidopsis thaliana, which has the best understood plant genome, still has approximately one-third of its genes with no functional annotation at all from either MIPS or TAIR. We have applied our Data Mining Prediction (DMP) method to the problem of predicting the functional classes of these protein sequences. This method is based on using a hybrid machine-learning/data-mining method to identify patterns in the bioinformatic data about sequences that are predictive of function. We use data about sequence, predicted secondary structure, predicted structural domain, InterPro patterns, sequence similarity profile and expressions data. RESULTS: We predicted the functional class of a high percentage of the Arabidopsis genes with currently unknown function. These predictions are interpretable and have good test accuracies. We describe in detail seven of the rules produced.

Algorithms↗

Graph-based analysis and visualization of experimental results with ONDEX.

MOTIVATION: Assembling the relevant information needed to interpret the output from high-throughput, genome scale, experiments such as gene expression microarrays is challenging. Analysis reveals genes that show statistically significant changes in expression levels, but more information is needed to determine their biological relevance. The challenge is to bring these genes together with biological information distributed across hundreds of databases or buried in the scientific literature (millions of articles). Software tools are needed to automate this task which at present is labor-intensive and requires considerable informatics and biological expertise. RESULTS: This article describes ONDEX and how it can be applied to the task of interpreting gene expression results. ONDEX is a database system that combines the features of semantic database integration and text mining with methods for graph-based analysis. An overview of the ONDEX system is presented, concentrating on recently developed features for graph-based analysis and visualization. A case study is used to show how ONDEX can help to identify causal relationships between stress response genes and metabolic pathways from gene expression data. ONDEX also discovered functional annotations for most of the genes that emerged as significant in the microarray experiment, but were previously of unknown function.

Algorithms↗

Annotating proteins by mining protein interaction networks.

MOTIVATION: In general, most accurate gene/protein annotations are provided by curators. Despite having lesser evidence strengths, it is inevitable to use computational methods for fast and a priori discovery of protein function annotations. This paper considers the problem of assigning Gene Ontology (GO) annotations to partially annotated or newly discovered proteins. RESULTS: We present a data mining technique that computes the probabilistic relationships between GO annotations of proteins on protein-protein interaction data, and assigns highly correlated GO terms of annotated proteins to non-annotated proteins in the target set. In comparison with other techniques, probabilistic suffix tree and correlation mining techniques produce the highest prediction accuracy of 81% precision with the recall at 45%. AVAILABILITY: Code is available upon request. Results and used materials are available online at http://kirac.case.edu/PROTAN.

Amino Acid Sequence↗

Integrating image data into biomedical text categorization.

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

Artificial Intelligence↗

Accessing bioscience images from abstract sentences.

Images (e.g., figures) are important experimental results that are typically reported in bioscience full-text articles. Biologists need to access images to validate research facts and to formulate or to test novel research hypotheses. On the other hand, biologists live in an age of information explosion. As thousands of biomedical articles are published every day, systems that help biologists efficiently access images in literature would greatly facilitate biomedical research. We hypothesize that much of image content reported in a full-text article can be summarized by the sentences in the abstract of the article. In our study, more than one hundred biologists had tested this hypothesis and more than 40 biologists had evaluated a novel user-interface BioEx that allows biologists to access images directly from abstract sentences. Our results show that 87.8% biologists were in favor of BioEx over two other baseline user-interfaces. We further developed systems that explored hierarchical clustering algorithms to automatically identify abstract sentences that summarize the images. One of the systems achieves a precision of 100% that corresponds to a recall of 4.6%.

Abstracting and Indexing↗

A top-level ontology of functions and its application in the Open Biomedical Ontologies.

MOTIVATION: A clear understanding of functions in biology is a key component in accurate modelling of molecular, cellular and organismal biology. Using the existing biomedical ontologies it has been impossible to capture the complexity of the community's knowledge about biological functions. RESULTS: We present here a top-level ontological framework for representing knowledge about biological functions. This framework lends greater accuracy, power and expressiveness to biomedical ontologies by providing a means to capture existing functional knowledge in a more formal manner. An initial major application of the ontology of functions is the provision of a principled way in which to curate functional knowledge and annotations in biomedical ontologies. Further potential applications include the facilitation of ontology interoperability and automated reasoning. A major advantage of the proposed implementation is that it is an extension to existing biomedical ontologies, and can be applied without substantial changes to these domain ontologies. AVAILABILITY: The Ontology of Functions (OF) can be downloaded in OWL format from http://onto.eva.mpg.de/. Additionally, a UML profile and supplementary information and guides for using the OF can be accessed from the same website.

Biomedical Engineering↗

Combination of text-mining algorithms increases the performance.

MOTIVATION: Recently, several information extraction systems have been developed to retrieve relevant information out of biomedical text. However, these methods represent individual efforts. In this paper, we show that by combining different algorithms and their outcome, the results improve significantly. For this reason, CONAN has been created, a system which combines different programs and their outcome. Its methods include tagging of gene/protein names, finding interaction and mutation data, tagging of biological concepts and linking to MeSH and Gene Ontology terms. RESULTS: In this paper, we will present data that show that combining different text-mining algorithms significantly improves the results. Not only is CONAN a full-scale approach that will ultimately cover all of PubMed/MEDLINE, we also show that this universality has no effect on quality: our system performs as well as or better than existing systems. AVAILABILITY: The LDD corpus presented is available by request to the author. The system will be available shortly. For information and updates on CONAN please visit http://www.cs.uu.nl/people/rainer/conan.html.

Abstracting and Indexing↗

Substring selection for biomedical document classification.

MOTIVATION: Attribute selection is a critical step in development of document classification systems. As a standard practice, words are stemmed and the most informative ones are used as attributes in classification. Owing to high complexity of biomedical terminology, general-purpose stemming algorithms are often conservative and could also remove informative stems. This can lead to accuracy reduction, especially when the number of labeled documents is small. To address this issue, we propose an algorithm that omits stemming and, instead, uses the most discriminative substrings as attributes. RESULTS: The approach was tested on five annotated sets of abstracts from iProLINK that report on the experimental evidence about five types of protein post-translational modifications. The experiments showed that Naive Bayes and support vector machine classifiers perform consistently better [with area under the ROC curve (AUC) accuracy in range 0.92-0.97] when using the proposed attribute selection than when using attributes obtained by the Porter stemmer algorithm (AUC in 0.86-0.93 range). The proposed approach is particularly useful when labeled datasets are small.

Abstracting and Indexing↗

Text similarity: an alternative way to search MEDLINE.

MOTIVATION: The most widely used literature search techniques, such as those offered by NCBI's PubMed system, require significant effort on the part of the searcher, and inexperienced searchers do not use these systems as effectively as experienced users. Improved literature search engines can save researchers time and effort by making it easier to locate the most important and relevant literature. RESULTS: We have created and optimized a new, hybrid search system for Medline that takes natural text as input and then delivers results with high precision and recall. The combination of a fast, low-sensitivity weighted keyword-based first pass algorithm to cast a wide net to gather an initial set of literature, followed by a unique sentence-alignment based similarity algorithm to rank order those results was developed that is sensitive, fast and easy to use. Several text similarity search algorithms, both standard and novel, were implemented and tested in order to determine which obtained the best results in information retrieval exercises. AVAILABILITY: Literature searching algorithms are implemented in a system called eTBLAST, freely accessible over the web at http://invention.swmed.edu. A variety of other derivative systems and visualization tools provides the user with an enhanced experience and additional capabilities. CONTACT: Harold.Garner@UTSouthwestern.edu.

Abstracting and Indexing↗

AliBaba: PubMed as a graph.

UNLABELLED: The biomedical literature contains a wealth of information on associations between many different types of objects, such as protein-protein interactions, gene-disease associations and subcellular locations of proteins. When searching such information using conventional search engines, e.g. PubMed, users see the data only one-abstract at a time and 'hidden' in natural language text. AliBaba is an interactive tool for graphical summarization of search results. It parses the set of abstracts that fit a PubMed query and presents extracted information on biomedical objects and their relationships as a graphical network. AliBaba extracts associations between cells, diseases, drugs, proteins, species and tissues. Several filter options allow for a more focused search. Thus, researchers can grasp complex networks described in various articles at a glance. AVAILABILITY: http://alibaba.informatik.hu-berlin.de/

Abstracting and Indexing↗

OSIRIS: a tool for retrieving literature about sequence variants.

UNLABELLED: Sequence variants, in particular single nucleotide polymorphisms (SNPs), are key elements for the identification of genes associated with complex diseases and with particular drug responses. The search for literature about sequence variation is hampered by the large number of allelic variants reported for many genes and by the variability in both gene and sequence variants nomenclatures. We describe OSIRIS, a search tool that integrates different sources of information with the aim to retrieve literature about sequence variation of a gene. In addition, it provides a method to link a dbSNP entry with the articles referring to it. AVAILABILITY: OSIRIS is available for public use at http://ibi.imim.es/

Abstracting and Indexing↗

ADAM: another database of abbreviations in MEDLINE.

MOTIVATION: Abbreviations are an important type of terminology in the biomedical domain. Although several groups have already created databases of biomedical abbreviations, these are either not public, or are not comprehensive, or focus exclusively on acronym-type abbreviations. We have created another abbreviation database, ADAM, which covers commonly used abbreviations and their definitions (or long-forms) within MEDLINE titles and abstracts, including both acronym and non-acronym abbreviations. RESULTS: A model of recognizing abbreviations and their long-forms from titles and abstracts of MEDLINE (2006 baseline) was employed. After grouping morphological variants, 59 405 abbreviation/long-form pairs were identified. ADAM shows high precision (97.4%) and includes most of the frequently used abbreviations contained in the Unified Medical Language System (UMLS) Lexicon and the Stanford Abbreviation Database. Conversely, one-third of abbreviations in ADAM are novel insofar as they are not included in either database. About 19% of the novel abbreviations are non-acronym-type and these cover at least seven different types of short-form/long-form pairs. AVAILABILITY: A free, public query interface to ADAM is available at http://arrowsmith.psych.uic.edu, and the entire database can be downloaded as a text file.

Animals↗

Building an abbreviation dictionary using a term recognition approach.

MOTIVATION: Acronyms result from a highly productive type of term variation and trigger the need for an acronym dictionary to establish associations between acronyms and their expanded forms. RESULTS: We propose a novel method for recognizing acronym definitions in a text collection. Assuming a word sequence co-occurring frequently with a parenthetical expression to be a potential expanded form, our method identifies acronym definitions in a similar manner to the statistical term recognition task. Applied to the whole MEDLINE (7 811 582 abstracts), the implemented system extracted 886 755 acronym candidates and recognized 300 954 expanded forms in reasonable time. Our method outperformed base-line systems, achieving 99% precision and 82-95% recall on our evaluation corpus that roughly emulates the whole MEDLINE. AVAILABILITY AND SUPPLEMENTARY INFORMATION: The implementations and supplementary information are available at our web site: http://www.chokkan.org/research/acromine/

Abbreviations as Topic↗

Using GOstats to test gene lists for GO term association.

MOTIVATION: Functional analyses based on the association of Gene Ontology (GO) terms to genes in a selected gene list are useful bioinformatic tools and the GOstats package has been widely used to perform such computations. In this paper we report significant improvements and extensions such as support for conditional testing. RESULTS: We discuss the capabilities of GOstats, a Bioconductor package written in R, that allows users to test GO terms for over or under-representation using either a classical hypergeometric test or a conditional hypergeometric that uses the relationships among GO terms to decorrelate the results. AVAILABILITY: GOstats is available as an R package from the Bioconductor project: http://bioconductor.org

Algorithms↗

Scanning an individual monitoring database for multiple occurrences using bi-gram analysis.

Maintaining the integrity of the databases is one of the important aspects of quality assurance at individual monitoring services and national dose registers. This paper presents a method for finding and preventing the occurrence of duplicate entries in the databases that can occur, e.g. because of a variable spelling or misspelling of the name. The method is based on bi-gram text analysis techniques. The methods can also be used for retrieving dose data in historical databases in the framework of dose reconstruction efforts of persons of whom the spelling of the name as originally entered, possibly decades ago, is uncertain.

Algorithms↗