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  • 1
    Language: English
    In: Algorithms for Molecular Biology, May 31, 2007, Vol.2(6), p.6
    Description: Motivation Genome-wide screens for structured ncRNA genes in mammals, urochordates, and nematodes have predicted thousands of putative ncRNA genes and other structured RNA motifs. A prerequisite for their functional annotation is to determine the reading direction with high precision. Results While folding energies of an RNA and its reverse complement are similar, the differences are sufficient at least in conjunction with substitution patterns to discriminate between structured RNAs and their complements. We present here a support vector machine that reliably classifies the reading direction of a structured RNA from a multiple sequence alignment and provides a considerable improvement in classification accuracy over previous approaches. Software RNAstrand is freely available as a stand-alone tool from http://www.bioinf.uni-leipzig.de/Software/RNAstrand and is also included in the latest release of RNAz, a part of the Vienna RNA Package.
    Keywords: Rna -- Research ; Rna -- Properties ; Transcription (Genetics) -- Research ; Transcription (Genetics) -- Methods ; Translation (Genetics) -- Research ; Translation (Genetics) -- Methods
    ISSN: 1748-7188
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  • 2
    Language: English
    In: Nature, March 11, 2010, Vol.463(7286), p.250(6)
    Description: Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ~60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
    Keywords: Antisense Rna -- Analysis ; Gene Expression -- Analysis ; Transcription (Genetics) -- Analysis ; Helicobacter Pylori -- Genetic Aspects ; Helicobacter Pylori -- Physiological Aspects
    ISSN: 0028-0836
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  • 3
    In: Nature, 2010, Vol.464(7286), p.250
    Description: Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
    Keywords: Gene Expression Profiling ; Genome, Bacterial -- Genetics ; Helicobacter Infections -- Microbiology ; Helicobacter Pylori -- Genetics ; RNA, Bacterial -- Genetics;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 4
    In: Bioinformatics, 2012, Vol. 28(11), pp.1471-1479
    Description: Motivation: Tiling arrays have been a mainstay of unbiased genome-wide transcriptomics over the last decade. Currently available approaches to identify expressed or differentially expressed segments in tiling array data are limited in the recovery of the underlying gene structures and require several parameters that are intensity-related or partly dataset-specific. We have developed , a statistical approach that identifies transcribed and differentially expressed segments as significant differences from the background distribution while considering sequence-specific affinity biases and cross-hybridization. It avoids dataset-specific parameters in order to provide better comparability of different tiling array datasets, based on different technologies or array designs. detects highly and differentially expressed segments in biological data with significantly lower false discovery rates under equal sensitivities than commonly used methods. Also, it is clearly superior in the recovery of exon–intron structures. It further provides window -scores as a normalized and robust measure for visual inspection. The R package including documentation and examples is freely available at 〈p〉〈bold〉Contact:〈/bold〉 〈email〉joerg.hackermueller@ufz.de〈/email〉〈/p〉 are available at online.
    Keywords: Biology;
    ISSN: 1367-4803
    ISSN: 13674811
    E-ISSN: 1460-2059
    E-ISSN: 13674811
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  • 5
    In: Toxicological Sciences, 2017, Vol. 157(2), pp.291-304
    Description: Numerous studies have been published in the past years investigating the transcriptome of the zebrafish embryo (ZFE) upon being subjected to chemical stress. Aiming at a more mechanistic understanding of the results of such studies, knowledge about commonalities of transcript regulation in response to chemical stress is needed. Thus, our goal in this study was to identify and interpret genes and gene sets constituting a general response to chemical exposure. Therefore, we aggregated and reanalyzed published toxicogenomics data obtained with the ZFE. We found that overlap of differentially transcribed genes in response to chemical stress across independent studies is generally low and the most commonly differentially transcribed genes appear in less than 50% of all treatments across studies. However, effect size analysis revealed several genes showing a common trend of differential expression, among which genes related to calcium homeostasis emerged as key, especially in exposure settings up to 24 h post-fertilization. Additionally, we found that these and other downregulated genes are often linked to anatomical regions developing during the respective exposure period. Genes showing a trend of increased expression were, among others, linked to signaling pathways (e.g., Wnt, Fgf) as well as lysosomal structures and apoptosis. The findings of this study help to increase the understanding of chemical stress responses in the developing zebrafish embryo and provide a starting point to improve experimental designs for this model system. In future, improved time- and concentration-resolved experiments should offer better understanding of stress response patterns and access to mechanistic information.
    Keywords: Meta - Analysis ; Microarray ; Stress Response ; Transcriptome ; Toxicogenomics ; Zebrafish Embryo
    ISSN: 1096-6080
    E-ISSN: 1096-0929
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(9), p.e106076
    Description: Breast cancer, the second leading cause of cancer death in women, is a highly heterogeneous disease, characterized by distinct genomic and transcriptomic profiles. Transcriptome analyses prevalently assessed protein-coding genes; however, the majority of the mammalian genome is expressed in numerous non-coding transcripts. Emerging evidence supports that many of these non-coding RNAs are specifically expressed during development, tumorigenesis, and metastasis. The focus of this study was to investigate the expression features and molecular characteristics of long non-coding RNAs (lncRNAs) in breast cancer. We investigated 26 breast tumor and 5 normal tissue samples utilizing a custom expression microarray enclosing probes for mRNAs as well as novel and previously identified lncRNAs. We identified more than 19,000 unique regions significantly differentially expressed between normal versus breast tumor tissue, half of these regions were non-coding without any evidence for functional open reading frames or sequence similarity to known proteins. The identified non-coding regions were primarily located in introns (53%) or in the intergenic space (33%), frequently orientated in antisense-direction of protein-coding genes (14%), and commonly distributed at promoter-, transcription factor binding-, or enhancer-sites. Analyzing the most diverse mRNA breast cancer subtypes Basal-like versus Luminal A and B resulted in 3,025 significantly differentially expressed unique loci, including 682 (23%) for non-coding transcripts. A notable number of differentially expressed protein-coding genes displayed non-synonymous expression changes compared to their nearest differentially expressed lncRNA, including an antisense lncRNA strongly anticorrelated to the mRNA coding for histone deacetylase 3 (HDAC3), which was investigated in more detail. Previously identified chromatin-associated lncRNAs (CARs) were predominantly downregulated in breast tumor samples, including CARs located in the protein-coding genes for CALD1, FTX, and HNRNPH1. In conclusion, a number of differentially expressed lncRNAs have been identified with relation to cancer-related protein-coding genes.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: Journal of Biotechnology, Nov 10, Vol.189, p.154(3)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jbiotec.2014.09.012 Byline: Christian Arnold, Fabian Externbrink, Jorg Hackermuller, Kristin Reiche Abstract: * We revisit custom expression microarray design in the face of complex transcriptomes. * We provide target selection methods accounting for different transcript biotypes. * We reduce cross-hybridization effects of probes to even yet unannotated targets. * We provide our selection methods as a freely available web server. Author Affiliation: (a) Bioinformatics Group, Department for Computer Science, University of Leipzig, Leipzig, Germany (b) Young Investigators Group, Bioinformatics and Transcriptomics, Department Proteomics, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany (c) RNomics Group, Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology - IZI, Leipzig, Germany Article History: Received 20 February 2014; Revised 2 September 2014; Accepted 17 September 2014
    ISSN: 0168-1656
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: Cytokine, 2011, Vol.56(1), pp.81-81
    Keywords: Medicine ; Biology
    ISSN: 1043-4666
    E-ISSN: 1096-0023
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  • 9
    Language: English
    In: The Journal of Urology, April 2016, Vol.195(4), pp.e10-e10
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2016.02.1875 Byline: Friedemann Horn, Sabina Christ-Breulmann, Sven-Holger Puppel, Tilo Buschmann, Kristin Reiche, Michael Specht, Catharina Bertram, Maik Friedrich, Stefanie Binder, Conny Blumert, Jorg Hackermuller, Markus Kreuz, Markus Loffler Author Affiliation: Leipzig, Germany Article Note: (footnote) Source of Funding: Fraunhofer Future Foundation
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 10
    Language: English
    In: Algorithms for Molecular Biology, April 20, 2013, Vol.8(1)
    Description: Background The search for distant homologs has become an import issue in genome annotation. A particular difficulty is posed by divergent homologs that have lost recognizable sequence similarity. This same problem also arises in the recognition of novel members of large classes of RNAs such as snoRNAs or microRNAs that consist of families unrelated by common descent. Current homology search tools for structured RNAs are either based entirely on sequence similarity (such as blast or hmmer) or combine sequence and secondary structure. The most prominent example of the latter class of tools is Infernal. Alternatives are descriptor-based methods. In most practical applications published to-date, however, the information contained in covariance models or manually prescribed search patterns is dominated by sequence information. Here we ask two related questions: (1) Is secondary structure alone informative for homology search and the detection of novel members of RNA classes? (2) To what extent is the thermodynamic propensity of the target sequence to fold into the correct secondary structure helpful for this task? Results Sequence-structure alignment can be used as an alternative search strategy. In this scenario, the query consists of a base pairing probability matrix, which can be derived either from a single sequence or from a multiple alignment representing a set of known representatives. Sequence information can be optionally added to the query. The target sequence is pre-processed to obtain local base pairing probabilities. As a search engine we devised a semi-global scanning variant of LocARNA's algorithm for sequence-structure alignment. The LocARNAscan tool is optimized for speed and low memory consumption. In benchmarking experiments on artificial data we observe that the inclusion of thermodynamic stability is helpful, albeit only in a regime of extremely low sequence information in the query. We observe, furthermore, that the sensitivity is bounded in particular by the limited accuracy of the predicted local structures of the target sequence. Conclusions Although we demonstrate that a purely structure-based homology search is feasible in principle, it is unlikely to outperform tools such as Infernal in most application scenarios, where a substantial amount of sequence information is typically available. The LocARNAscan approach will profit, however, from high throughput methods to determine RNA secondary structure. In transcriptome-wide applications, such methods will provide accurate structure annotations on the target side. Availability Source code of the free software LocARNAscan 1.0 and supplementary data are available athttp://www.bioinf.uni-leipzig.de/Software/LocARNAscan.
    Keywords: Thermodynamics – Analysis ; Genomes – Analysis ; RNA – Analysis ; Genomics – Analysis
    ISSN: 1748-7188
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