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  • 1
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    Weighted enrichment method for prediction of transcription regulators from transcriptome and global chromatin immunoprecipitation data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-21
    Description: Predicting responsible transcription regulators on the basis of transcriptome data is one of the most promising computational approaches to understanding cellular processes and characteristics. Here, we present a novel method employing vast amounts of chromatin immunoprecipitation (ChIP) experimental data to address this issue. Global high-throughput ChIP data was collected to construct a comprehensive database, containing 8 578 738 binding interactions of 454 transcription regulators. To incorporate information about heterogeneous frequencies of transcription factor (TF)-binding events, we developed a flexible framework for gene set analysis employing the weighted t -test procedure, namely weighted parametric gene set analysis (wPGSA). Using transcriptome data as an input, wPGSA predicts the activities of transcription regulators responsible for observed gene expression. Validation of wPGSA with published transcriptome data, including that from over-expressed TFs, showed that the method can predict activities of various TFs, regardless of cell type and conditions, with results totally consistent with biological observations. We also applied wPGSA to other published transcriptome data and identified potential key regulators of cell reprogramming and influenza virus pathogenesis, generating compelling hypotheses regarding underlying regulatory mechanisms. This flexible framework will contribute to uncovering the dynamic and robust architectures of biological regulation, by incorporating high-throughput experimental data in the form of weights.
    Keywords: Genomics, Transcriptome Mapping - Monitoring Gene Expression
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Cell line name recognition in support of the identification of synthetic lethality in cancer from text (2016)
    Oxford University Press
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    Publication Date: 2016-01-10
    Description: Motivation: The recognition and normalization of cell line names in text is an important task in biomedical text mining research, facilitating for instance the identification of synthetically lethal genes from the literature. While several tools have previously been developed to address cell line recognition, it is unclear whether available systems can perform sufficiently well in realistic and broad-coverage applications such as extracting synthetically lethal genes from the cancer literature. In this study, we revisit the cell line name recognition task, evaluating both available systems and newly introduced methods on various resources to obtain a reliable tagger not tied to any specific subdomain. In support of this task, we introduce two text collections manually annotated for cell line names: the broad-coverage corpus Gellus and CLL, a focused target domain corpus. Results: We find that the best performance is achieved using NERsuite, a machine learning system based on Conditional Random Fields, trained on the Gellus corpus and supported with a dictionary of cell line names. The system achieves an F-score of 88.46% on the test set of Gellus and 85.98% on the independently annotated CLL corpus. It was further applied at large scale to 24 302 102 unannotated articles, resulting in the identification of 5 181 342 cell line mentions, normalized to 11 755 unique cell line database identifiers. Availability and implementation: The manually annotated datasets, the cell line dictionary, derived corpora, NERsuite models and the results of the large-scale run on unannotated texts are available under open licenses at http://turkunlp.github.io/Cell-line-recognition/ . Contact: sukaew@utu.fi
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 3
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    Event extraction across multiple levels of biological organization (2012)
    Oxford University Press
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    Publication Date: 2012-09-08
    Description: Motivation: Event extraction using expressive structured representations has been a significant focus of recent efforts in biomedical information extraction. However, event extraction resources and methods have so far focused almost exclusively on molecular-level entities and processes, limiting their applicability. Results: We extend the event extraction approach to biomedical information extraction to encompass all levels of biological organization from the molecular to the whole organism. We present the ontological foundations, target types and guidelines for entity and event annotation and introduce the new multi-level event extraction (MLEE) corpus, manually annotated using a structured representation for event extraction. We further adapt and evaluate named entity and event extraction methods for the new task, demonstrating that both can be achieved with performance broadly comparable with that for established molecular entity and event extraction tasks. Availability: The resources and methods introduced in this study are available from http://nactem.ac.uk/MLEE/ . Contact: pyysalos@cs.man.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    The influence of meteorology and phenology on net ecosystem exchange in an eastern Siberian boreal larch forest (2016)
    Oxford University Press
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    Publication Date: 2016-09-21
    Description: Aims Boreal forests play an important role in the global carbon cycle. Compared with the boreal forests in North America and Europe, relatively few research studies have been conducted in Siberian boreal forests. Knowledge related to the role of Siberian forests in the global carbon balance is thus essential for a full understanding of global carbon cycle. Methods This study investigated the net ecosystem exchange (NEE) during growing season (May–September) in an eastern Siberian boreal larch forest for a 3-year period in 2004–2006 with contrasting meteorological conditions. Important Findings The study found that the forest served as a carbon sink during all of the 3 studied years; in addition, the meteorological conditions essentially influenced the specific annual value of the strength of the carbon sinks in each year. Although 2005 was the warmest year and much wetter than 2004, 2005 also featured the greatest amount of ecosystem respiration, which resulted in a minimum value of NEE. The study also found that the phenological changes observed during the three study years had a relatively small effect on annual NEE. Leaf expansion was 26 days earlier in 2005 than in the other 2 years, which resulted in a longer growing season in 2005. However, the NEE in 2005 was counterbalanced by the large rate of ecosystem respiration that was caused by the higher temperatures in the year. This study showed that meteorological variables had larger influences on the interannual variations in NEE for a Siberian boreal larch forest, as compared with phenological changes. The overall results of this study will improve our understanding of the carbon balance of Siberian boreal larch forests and thus can help to forecast the response of these forests to future climate change.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct, catalysed by human DNA polymerases (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-20
    Description: Many chronic inflammatory conditions are associated with an increased risk of cancer development. At the site of inflammation, cellular DNA is damaged by hypochlorous acid (HOCl), a potent oxidant generated by myeloperoxidase. 8-Chloro-2'-deoxyguanosine (8-Cl-dG) is a major DNA adduct formed by HOCl and has been detected from the liver DNA and urine of rats administered lipopolysaccharide in an inflammation model. Thus, the 8-Cl-dG lesion may be associated with the carcinogenesis of inflamed tissues. In this study, we explored the miscoding properties of the 8-Cl-dG adduct generated by human DNA polymerases (pols). Site-specifically modified oligodeoxynucleotide containing a single 8-Cl-dG was prepared and used as a template in primer extension reactions catalysed by human pol α, or . Primer extension reactions catalysed by pol α and in the presence of all four dNTPs were slightly retarded at the 8-Cl-dG site, while pol readily bypassed the lesion. The fully extended products were analysed to quantify the miscoding frequency and specificity of 8-Cl-dG using two-phased polyacrylamide gel electrophoresis (PAGE). During the primer extension reaction in the presence of four dNTPs, pol promoted one-base deletion (6.4%), accompanied by the misincorporation of 2'-deoxyguanosine monophosphate (5.5%), dAMP (3.7%), and dTMP (3.5%) opposite the lesion. Pol α and , on the other hand, exclusively incorporated dCMP opposite the lesion. The steady-state kinetic studies supported the results obtained from the two-phased PAGE assay. These results indicate that 8-Cl-dG is a mutagenic lesion; the miscoding frequency and specificity varies depending on the DNA polymerase used. Thus, HOCl-induced 8-Cl-dG adduct may be involved in inflammation-driven carcinogenesis.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text (2013)
    Oxford University Press
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    Publication Date: 2013-06-24
    Description: Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/ . Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 7
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    Heat and Noxious Chemical Sensor, Chicken TRPA1, as a Target of Bird Repellents and Identification of Its Structural Determinants by Multispecies Functional Comparison (2014)
    Oxford University Press
    Details
    Publication Date: 2014-02-27
    Description: Nociceptive receptors enable animals to sense tissue-damaging stimuli, thus playing crucial roles in survival. Due to evolutionary diversification, responses of nociceptive receptors to specific stimuli can vary among species. Multispecies functional comparisons of nociceptive receptors help elucidate their evolutionary process and molecular basis for activation. The transient receptor potential ankyrin 1 (TRPA1) ion channel serves as a nociceptive receptor for chemical and thermal stimuli that is heat-activated in reptiles and frogs while potentially cold-activated in rodents. Here, we characterized channel properties of avian TRPA1 in chicken. Chicken TRPA1 was activated by noxious chemicals that also activate TRPA1 in other vertebrates. Regarding thermal sensitivity, chicken TRPA1 was activated by heat stimulation, but not cold, thus thermal sensitivity of avian TRPA1 does not coincide with rodent TRPA1, although both are homeotherms. Furthermore, in chicken sensory neurons, TRPA1 was highly coexpressed with TRPV1, another nociceptive heat and chemical receptor, similar to mammals and frogs. These results suggest that TRPA1 acted as a noxious chemical and heat receptor, and was coexpressed with TRPV1 in the ancestral terrestrial vertebrate. The acquisition of TRPV1 as a novel heat receptor in the ancestral terrestrial vertebrate is likely to have affected the functional evolution of TRPA1 regarding thermal sensitivity and led to the diversification among diverse vertebrate species. Additionally, we found for the first time that chicken TRPA1 is activated by methyl anthranilate (MA) and its structurally related chemicals used as nonlethal bird repellents. MA-induced responses were abolished by a TRPA1 antagonist in somatosensory neurons, indicating that TRPA1 acts as a MA receptor in chicken. Furthermore, TRPA1 responses to MA varied among five diverse vertebrate species. Utilizing species diversity and mutagenesis experiments, three amino acids were identified as critical residues for MA-induced activation of chicken TRPA1.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Mutagenicity of UV-irradiated maltol in Salmonella typhimurium (2006)
    Oxford University Press
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    Publication Date: 2006-12-08
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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     -Glucosidase as a reporter for the gene expression studies in Thermus thermophilus and constitutive expression of DNA repair genes (2006)
    Oxford University Press
    Details
    Publication Date: 2006-05-30
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    GENIA corpus--a semantically annotated corpus for bio-textmining (2003)
    Oxford University Press
    Details
    Publication Date: 2003-07-03
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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