A realistic assessment of methods for extracting gene/protein interactions from free text

Background: The automated extraction of gene and/or protein interactions from the literature is one of the most important targets of biomedical text mining research. In this paper we present a realistic evaluation of gene/protein interaction mining relevant to potential non-specialist users. Hence we have specifically avoided methods that are complex to install or require reimplementation, and we coupled our chosen extraction methods with a state-of-the-art biomedical named entity tagger. Results: Our results show: that performance across different evaluation corpora is extremely variable; that the use of tagged (as opposed to gold standard) gene and protein names has a significant impact on performance, with a drop in F-score of over 20 percentage points being commonplace; and that a simple keyword-based benchmark algorithm when coupled with a named entity tagger outperforms two of the tools most widely used to extract gene/protein interactions. Conclusion: In terms of availability, ease of use and performance, the potential non-specialist user community interested in automatically extracting gene and/or protein interactions from free text is poorly served by current tools and systems. The public release of extraction tools that are easy to install and use, and that achieve state-of-art levels of performance should be treated as a high priority by the biomedical text mining community

Identification of transcription factor contexts in literature using machine learning approaches

Background: Availability of information about transcription factors (TFs) is crucial for genome biology, as TFs play a central role in the regulation of gene expression. While manual literature curation is expensive and labour intensive, the development of semi-automated text mining support is hindered by unavailability of training data. There have been no studies on how existing data sources (e.g. TF-related data from the MeSH thesaurus and GO ontology) or potentially noisy example data (e.g. protein-protein interaction, PPI) could be used to provide training data for identification of TF-contexts in literature. Results: In this paper we describe a text-classification system designed to automatically recognise contexts related to transcription factors in literature. A learning model is based on a set of biological features (e.g. protein and gene names, interaction words, other biological terms) that are deemed relevant for the task. We have exploited background knowledge from existing biological resources (MeSH and GO) to engineer such features. Weak and noisy training datasets have been collected from descriptions of TF-related concepts in MeSH and GO, PPI data and data representing non-protein-function descriptions. Three machine-learning methods are investigated, along with a vote-based merging of individual approaches and/or different training datasets. The system achieved highly encouraging results, with most classifiers achieving an F-measure above 90%. Conclusions: The experimental results have shown that the proposed model can be used for identification of TF-related contexts (i.e. sentences) with high accuracy, with a significantly reduced set of features when compared to traditional bag-of-words approach. The results of considering existing PPI data suggest that there is not as high similarity between TF and PPI contexts as we have expected. We have also shown that existing knowledge sources are useful both for feature engineering and for obtaining noisy positive training data

PathBinder – text empirics and automatic extraction of biomolecular interactions

Motivation 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. Results 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. Conclusion The text empirics approach used here supports computationally friendly, performance competitive, automatic extraction of biomolecular interactions from texts

Automatic extraction of biomolecular interactions: an empirical approach

Background We describe a method for extracting data about how biomolecule pairs interact from texts. This method relies on empirically determined characteristics of sentences. The characteristics are efficient to compute, making this approach to extraction of biomolecular interactions scalable. The results of such interaction mining can support interaction network annotation, question answering, database construction, and other applications. Results We constructed a software system to search MEDLINE for sentences likely to describe interactions between given biomolecules. The system extracts a list of the interaction-indicating terms appearing in those sentences, then ranks those terms based on their likelihood of correctly characterizing how the biomolecules interact. The ranking process uses a tf-idf (term frequency-inverse document frequency) based technique using empirically derived knowledge about sentences, and was applied to the MEDLINE literature collection. Software was developed as part of the MetNet toolkit (http://www.metnetdb.org). Conclusions Specific, efficiently computable characteristics of sentences about biomolecular interactions were analyzed to better understand how to use these characteristics to extract how biomolecules interact. The text empirics method that was investigated, though arising from a classical tradition, has yet to be fully explored for the task of extracting biomolecular interactions from the literature. The conclusions we reach about the sentence characteristics investigated in this work, as well as the technique itself, could be used by other systems to provide evidence about putative interactions, thus supporting efforts to maximize the ability of hybrid systems to support such tasks as annotating and constructing interaction networks

An application in bioinformatics : a comparison of affymetrix and compugen human genome microarrays

The human genome microarrays from Compugen® and Affymetrix® were compared in the context of the emerging field of computational biology. The two premier database servers for genomic sequence data, the National Center for Biotechnology Information and the European Bioinformatics Institute, were described in detail. The various databases and data mining tools available through these data servers were also discussed. Microarrays were examined from a historical perspective and their main current applications-expression analysis, mutation analysis, and comparative genomic hybridization-were discussed. The two main types of microarrays, cDNA spotted microarrays and high-density spotted microarrays were analyzed by exploring the human genome microarray from Compugen® and the HGU133 Set from Affymetrix® respectively. Array design issues, sequence collection and analysis, and probe selection processes for the two representative types of arrays were described. The respective chip design of the two types of microarrays was also analyzed. It was found that the human genome microarray from Compugen 0 contains probes that interrogate 1,119,840 bases corresponding to 18,664 genes, while the HG-U133 Set from Affymetrix® contains probes that interrogate only 825,000 bases corresponding to 33,000 genes. Based on this, the efficiency of the 25-mer probes of the HG-U133 Set from Affymetrix® compared to the 60-mer probes of the microarray from Compugen® was questioned

Benchmarking natural-language parsers for biological applications using dependency graphs

BACKGROUND: Interest is growing in the application of syntactic parsers to natural language processing problems in biology, but assessing their performance is difficult because differences in linguistic convention can falsely appear to be errors. We present a method for evaluating their accuracy using an intermediate representation based on dependency graphs, in which the semantic relationships important in most information extraction tasks are closer to the surface. We also demonstrate how this method can be easily tailored to various application-driven criteria. RESULTS: Using the GENIA corpus as a gold standard, we tested four open-source parsers which have been used in bioinformatics projects. We first present overall performance measures, and test the two leading tools, the Charniak-Lease and Bikel parsers, on subtasks tailored to reflect the requirements of a system for extracting gene expression relationships. These two tools clearly outperform the other parsers in the evaluation, and achieve accuracy levels comparable to or exceeding native dependency parsers on similar tasks in previous biological evaluations. CONCLUSION: Evaluating using dependency graphs allows parsers to be tested easily on criteria chosen according to the semantics of particular biological applications, drawing attention to important mistakes and soaking up many insignificant differences that would otherwise be reported as errors. Generating high-accuracy dependency graphs from the output of phrase-structure parsers also provides access to the more detailed syntax trees that are used in several natural-language processing techniques

Text Mining and Gene Expression Analysis Towards Combined Interpretation of High Throughput Data

Microarrays can capture gene expression activity for thousands of genes simultaneously and thus make it possible to analyze cell physiology and disease processes on molecular level. The interpretation of microarray gene expression experiments profits from knowledge on the analyzed genes and proteins and the biochemical networks in which they play a role. The trend is towards the development of data analysis methods that integrate diverse data types. Currently, the most comprehensive biomedical knowledge source is a large repository of free text articles. Text mining makes it possible to automatically extract and use information from texts. This thesis addresses two key aspects, biomedical text mining and gene expression data analysis, with the focus on providing high-quality methods and data that contribute to the development of integrated analysis approaches. The work is structured in three parts. Each part begins by providing the relevant background, and each chapter describes the developed methods as well as applications and results. Part I deals with biomedical text mining: Chapter 2 summarizes the relevant background of text mining; it describes text mining fundamentals, important text mining tasks, applications and particularities of text mining in the biomedical domain, and evaluation issues. In Chapter 3, a method for generating high-quality gene and protein name dictionaries is described. The analysis of the generated dictionaries revealed important properties of individual nomenclatures and the used databases (Fundel and Zimmer, 2006). The dictionaries are publicly available via a Wiki, a web service, and several client applications (Szugat et al., 2005). In Chapter 4, methods for the dictionary-based recognition of gene and protein names in texts and their mapping onto unique database identifiers are described. These methods make it possible to extract information from texts and to integrate text-derived information with data from other sources. Three named entity identification systems have been set up, two of them building upon the previously existing tool ProMiner (Hanisch et al., 2003). All of them have shown very good performance in the BioCreAtIvE challenges (Fundel et al., 2005a; Hanisch et al., 2005; Fundel and Zimmer, 2007). In Chapter 5, a new method for relation extraction (Fundel et al., 2007) is presented. It was applied on the largest collection of biomedical literature abstracts, and thus a comprehensive network of human gene and protein relations has been generated. A classification approach (Küffner et al., 2006) can be used to specify relation types further; e. g., as activating, direct physical, or gene regulatory relation. Part II deals with gene expression data analysis: Gene expression data needs to be processed so that differentially expressed genes can be identified. Gene expression data processing consists of several sequential steps. Two important steps are normalization, which aims at removing systematic variances between measurements, and quantification of differential expression by p-value and fold change determination. Numerous methods exist for these tasks. Chapter 6 describes the relevant background of gene expression data analysis; it presents the biological and technical principles of microarrays and gives an overview of the most relevant data processing steps. Finally, it provides a short introduction to osteoarthritis, which is in the focus of the analyzed gene expression data sets. In Chapter 7, quality criteria for the selection of normalization methods are described, and a method for the identification of differentially expressed genes is proposed, which is appropriate for data with large intensity variances between spots representing the same gene (Fundel et al., 2005b). Furthermore, a system is described that selects an appropriate combination of feature selection method and classifier, and thus identifies genes which lead to good classification results and show consistent behavior in different sample subgroups (Davis et al., 2006). The analysis of several gene expression data sets dealing with osteoarthritis is described in Chapter 8. This chapter contains the biomedical analysis of relevant disease processes and distinct disease stages (Aigner et al., 2006a), and a comparison of various microarray platforms and osteoarthritis models. Part III deals with integrated approaches and thus provides the connection between parts I and II: Chapter 9 gives an overview of different types of integrated data analysis approaches, with a focus on approaches that integrate gene expression data with manually compiled data, large-scale networks, or text mining. In Chapter 10, a method for the identification of genes which are consistently regulated and have a coherent literature background (Küffner et al., 2005) is described. This method indicates how gene and protein name identification and gene expression data can be integrated to return clusters which contain genes that are relevant for the respective experiment together with literature information that supports interpretation. Finally, in Chapter 11 ideas on how the described methods can contribute to current research and possible future directions are presented

New data analytics and visualization methods in personal data mining, cancer data analysis and sports data visualization

In this dissertation, we discuss a reading profiling system, a biological data visualization system and a sports visualization system. Self-tracking is getting increasingly popular in the field of personal informatics. Reading profiling can be used as a personal data collection method. We present UUAT, an unintrusive user attention tracking system. In UUAT, we used user interaction data to develop technologies that help to pinpoint a users reading region (RR). Based on computed RR and user interaction data, UUAT can identify a readers reading struggle or interest. A biomarker is a measurable substance that may be used as an indicator of a particular disease. We developed CancerVis for visual and interactive analysis of cancer data and demonstrate how to apply this platform in cancer biomarker research. CancerVis provides interactive multiple views from different perspectives of a dataset. The views are synchronized so that users can easily link them to a same data entry. Furthermore, CancerVis supports data mining practice in cancer biomarker, such as visualization of optimal cutpoints and cutthrough exploration. Tennis match summarization helps after-live sports consumers assimilate an interested match. We developed TennisVis, a comprehensive match summarization and visualization platform. TennisVis offers chart- graph for a client to quickly get match facts. Meanwhile, TennisVis offers various queries of tennis points to satisfy diversified client preferences (such as volley shot, many-shot rally) of tennis fans. Furthermore, TennisVis offers video clips for every single tennis point and a recommendation rating is computed for each tennis play. A case study shows that TennisVis identifies more than 75% tennis points in full time match

Computational and experimental analysis of TAL effector-DNA binding

TAL effectors, from the plant-pathogenic bacterial genus Xanthomonas, are DNA binding proteins that can be engineered to bind to almost any sequence of interest. The DNA target of the TAL effector is encoded by a modular central repeat region, with each repeat specifying a single binding site nucleotide. TAL effectors can be targeted to novel DNA sequences by assembling the corresponding repeat sequence. Therefore, custom TAL effectors have become important tools for manipulating gene expression and creating site-specific DNA modifications. This dissertation explores TAL effector-DNA binding through computational and experimental analyses. I identified positional and composition biases in known TAL effector-target pairs and proposed guidelines for designing custom TAL effectors and TAL effector nucleases (TALENs). Using these guidelines, I created a software tool for TAL effector design. We expanded this tool into a suite of tools for TAL effector/TALEN design and target site prediction. Target site predictions can be used to estimate potential off-target binding of custom TAL effector constructs or to identify unknown targets of natural TAL effectors. Next, I present a case study in engineering disease resist rice plants. Inserting multiple TAL effector binding elements (EBEs) into the promoter of a rice resistance gene conferred resistance to diverse strains of Xanthomonas oryzae. Analysis of the EBE sequences revealed that TAL effectors have evolved to target specific host regulatory sequences, and caution is warranted when introducing such sequences into the promoter of an executor resistance gene. Finally, I examine the role of the TAL effector N terminus in DNA binding. Most natural TAL effector binding sites are preceded by a T at the 5\u27 end (T0). Structural data suggests T0 is encoded by tryptophan 232 (W232) in the cryptic -1st repeat. We show that substitutions for W232 alter TAL effector activity and specificity for T0. However, we find that the TAL effector-T0 interaction is complex and may depend on other residues in the -1st repeat, the 0th cryptic repeat, or repeat sequence context. Better understanding of TAL effector-DNA binding will improve TAL effector design and target prediction and enhance understanding of the role of TAL effectors in plant disease