Authors: Type:

2019

  • [DOI] A. Viehweger, S. Krautwurst, K. Lamkiewicz, R. Madhugiri, J. Ziebuhr, M. Hölzer, and M. Marz, “Direct rna nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis.,” Genome Res, p. 483693, 2019.
    [Bibtex]
    @Article{Viehweger:19a,
    author = {Adrian Viehweger and Sebastian Krautwurst and Kevin Lamkiewicz and Ramakanth Madhugiri and John Ziebuhr and Martin H\"{o}lzer and Manja Marz},
    title = {Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis.},
    journal = {{Genome Res}},
    year = {2019},
    pages = {483693},
    doi = {10.1101/gr.247064.118},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] A. Viehweger, S. Krautwurst, B. Koenig, and M. Marz, “Distributed representations of protein domains and genomes and their compositionality,” bioRxiv, p. 524280, 2019.
    [Bibtex]
    @Article{Viehweger:19,
    author = {Adrian Viehweger and Sebastian Krautwurst and Brigitte Koenig and Manja Marz},
    title = {Distributed representations of protein domains and genomes and their compositionality},
    journal = {{bioRxiv}},
    year = {2019},
    pages = {524280},
    doi = {10.1101/524280},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] P. Sieber, E. Barth, and M. Marz, “The landscape of the alternatively spliced transcriptome remains stable during aging across different species and tissues,” bioRxiv, p. 541417, 2019.
    [Bibtex]
    @Article{Sieber:19,
    author = {Patricia Sieber and Emanuel Barth and Manja Marz},
    title = {The landscape of the alternatively spliced transcriptome remains stable during aging across different species and tissues},
    journal = {{bioRxiv}},
    year = {2019},
    pages = {541417},
    doi = {10.1101/541417},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] C. Wegner, M. Gaspar, P. Geesink, M. Herrmann, M. Marz, and K. Küsel, “Biogeochemical regimes in shallow aquifers reflect the metabolic coupling of elements of nitrogen, sulfur and carbon.,” Appl Environ Microbiol, vol. 85, iss. 5, p. e02346-18, 2019.
    [Bibtex]
    @Article{Wegner:19,
    author = {Wegner, Carl-Eric and Gaspar, Michael and Geesink, Patricia and Herrmann, Martina and Marz, Manja and Küsel, Kirsten},
    title = {Biogeochemical regimes in shallow aquifers reflect the metabolic coupling of elements of nitrogen, sulfur and carbon.},
    journal = {{Appl Environ Microbiol}},
    year = {2019},
    volume = {85},
    number = {5},
    pages = {e02346-18},
    abstract = {Near-surface groundwaters are prone to receive (in)organic matter input from their recharge areas and are known to harbour autotrophic microbial communities linked to nitrogen and sulfur metabolism. Here, we use multi-"omic" profiling to gain holistic insights into the turnover of inorganic nitrogen compounds, carbon fixation processes and organic matter processing in groundwater. We sampled microbial biomass from two superimposed aquifers via monitoring wells that follow groundwater flow from its recharge area through differences in hydrogeochemical settings and land use. Functional profiling revealed that groundwater microbiomes are mainly driven by nitrogen (nitrification, denitrification, anammox) and to a lesser extent sulfur cycling (sulfur oxidation and sulfate reduction), dependent on local hydrochemical differences. Surprisingly, the differentiation potential of the groundwater microbiome surpasses that of hydrochemistry for individual monitoring wells. Dominated by few phyla (Bacteroidetes, Proteobacteria, Planctomycetes, Thaumarchaeota), the taxonomic profiling of groundwater metagenomes and metatranscriptomes revealed pronounced differences between merely present microbiome members and those actively participating in community gene expression and biogeochemical cycling. Unexpectedly, we observed a constitutive expression of carbohydrate-active enzymes, encoded by different microbiome members, along with the groundwater flow path. The turnover of organic carbon apparently complements for lithoautotrophic carbon assimilation pathways mainly used by the groundwater microbiome dependent on the availability of oxygen and inorganic electron donors like ammonium. Groundwater is a key resource for drinking water production and irrigation. The interplay between geological setting, hydrochemistry, carbon storage and groundwater microbiome ecosystem functioning is crucial for our understanding of these important ecosystem services. We targeted the encoded and expressed metabolic potential of groundwater microbiomes along an aquifer transect that diversifies in terms of hydrochemistry and land use. Our results showed that the groundwater microbiome has a higher spatial differentiation potential than hydrochemistry.},
    doi = {10.1128/AEM.02346-18},
    pmid = {30578263},
    }
  • [DOI] F. Mock, A. Viehweger, E. Barth, and M. Marz, “Viral host prediction with deep learning,” Biorxiv, 2019.
    [Bibtex]
    @article {Mock:19,
    author = {Mock, Florian and Viehweger, Adrian and Barth, Emanuel and Marz, Manja},
    title = {Viral host prediction with Deep Learning},
    elocation-id = {575571},
    year = {2019},
    doi = {10.1101/575571},
    publisher = {Cold Spring Harbor Laboratory},
    abstract = {Zoonosis, the natural transmission of infections from animal to human, is a far-reaching global problem. The recent outbreaks of Zika virus and Ebola virus are examples of viral zoonosis, which occur more frequently due to globalization. In case of a virus outbreak, it is helpful to know which host organism was the original carrier of the virus. Once the reservoir or intermediate host is known, it can be isolated to prevent further spreading of the viral infection. Recent approaches aim to predict a viral host based on the viral genome, often in combination with the potential host genome and using arbitrary selected features. This methods have a clear limitation in either the amount of different hosts they can predict or the accuracy of the prediction. Here, we present a fast and accurate deep learning approach for viral host prediction, which is based on the viral genome sequence only. To assure a high prediction accuracy we developed an effective selection approach for the training data, to avoid biases due to a highly unbalanced number of known sequences per virus-host combinations. We tested our deep neural network on three different virus species (influenza A virus, rabies lyssavirus, rotavirus A) and reached for each virus species a AUC between 0.94 and 0.98, outperforming previous approaches and allowing highly accurate predictions while only using fractions of the viral genome sequences. We show that deep neural networks are suitable to predict the host of a virus, even with a limited amount of sequences and highly unbalanced available data. The deep neural networks trained for this approach build the core of the virus host predicting tool VIDHOP (VIrus Deep learning HOst Prediction).},
    journal = {bioRxiv}
    }
  • [DOI] G. Gerresheim, J. Bathke, A. Michel, D. Andreev, L. Shalamova, O. Rossbach, P. Hu, D. Glebe, M. Fricke, M. Marz, A. Goesmann, S. Kiniry, P. Baranov, I. Shatsky, and M. Niepmann, “Cellular gene expression during hepatitis C virus replication as revealed by ribosome profiling,” Int J Mol Sci, vol. 20, iss. 6, p. 1321, 2019.
    [Bibtex]
    @Article{Gerresheim:19,
    author = {Gesche Gerresheim and Jochen Bathke and Audrey Michel and Dmitri Andreev and Lyudmila Shalamova and Oliver Rossbach and Pan Hu and Dieter Glebe and Markus Fricke and Manja Marz and Alexander Goesmann and Stephen Kiniry and Pavel Baranov and Ivan Shatsky and Michael Niepmann},
    title = {Cellular Gene Expression during Hepatitis {C} Virus Replication as Revealed by Ribosome Profiling},
    journal = {{Int J Mol Sci}},
    year = {2019},
    volume = {20},
    number = {6},
    pages = {1321},
    doi = {10.3390/ijms20061321},
    publisher = {{MDPI} {AG}},
    }
  • [DOI] F. Hufsky, B. Ibrahim, S. Modha, M. R. J. Clokie, S. Deinhardt-Emmer, B. E. Dutilh, S. Lycett, P. Simmonds, V. Thiel, A. Abroi, E. M. Adriaenssens, M. Escalera-Zamudio, J. N. Kelly, K. Lamkiewicz, L. Lu, J. Susat, T. Sicheritz, D. L. Robertson, and M. Marz, “The third annual meeting of the European Virus Bioinformatics Center,” Viruses, vol. 11, iss. 5, p. 420, 2019.
    [Bibtex]
    @Article{Hufsky:19,
    author = {Franziska Hufsky and Bashar Ibrahim and Sejal Modha and Martha R. J. Clokie and Stefanie Deinhardt-Emmer and Bas E. Dutilh and Samantha Lycett and Peter Simmonds and Volker Thiel and Aare Abroi and Evelien M. Adriaenssens and Marina Escalera-Zamudio and Jenna Nicole Kelly and Kevin Lamkiewicz and Lu Lu and Julian Susat and Thomas Sicheritz and David L. Robertson and Manja Marz},
    title = {The Third Annual Meeting of the {E}uropean {V}irus {B}ioinformatics {C}enter},
    journal = {Viruses},
    year = {2019},
    volume = {11},
    number = {5},
    pages = {420},
    doi = {10.3390/v11050420},
    publisher = {{MDPI} {AG}},
    }
  • [DOI] M. Hölzer and M. Marz, “De novo transcriptome assembly: a comprehensive cross-species comparison of short-read RNA-seq assemblers,” GigaScience, vol. 8, iss. 5, 2019.
    [Bibtex]
    @Article{Hölzer:19,
    author = {Martin Hölzer and Manja Marz},
    title = {{De novo} transcriptome assembly: A comprehensive cross-species comparison of short-read {RNA}-Seq assemblers},
    journal = {{GigaScience}},
    year = {2019},
    volume = {8},
    number = {5},
    doi = {10.1093/gigascience/giz039},
    publisher = {Oxford University Press ({OUP})},
    }
  • [DOI] S. Peter, M. Hölzer, K. Lamkiewicz, P. S. di Fenizio, H. A. Hwaeer, M. Marz, S. Schuster, P. Dittrich, and B. Ibrahim, “Structure and hierarchy of influenza virus models revealed by reaction network analysis,” Viruses, vol. 11, iss. 5, p. 449, 2019.
    [Bibtex]
    @Article{Peter:19,
    author = {Stephan Peter and Martin Hölzer and Kevin Lamkiewicz and Pietro Speroni di Fenizio and Hassan Al Hwaeer and Manja Marz and Stefan Schuster and Peter Dittrich and Bashar Ibrahim},
    title = {Structure and Hierarchy of Influenza Virus Models Revealed by Reaction Network Analysis},
    journal = {Viruses},
    year = {2019},
    volume = {11},
    number = {5},
    pages = {449},
    doi = {10.3390/v11050449},
    publisher = {{MDPI} {AG}},
    }
  • [DOI] R. Kallies, M. Hölzer, R. Brizola Toscan, U. Nunes da Rocha, J. Anders, M. Marz, and A. Chatzinotas, “Evaluation of sequencing library preparation protocols for viral metagenomic analysis from pristine aquifer groundwaters.,” Viruses, vol. 11, 2019.
    [Bibtex]
    @Article{Kallies:19,
    author = {Kallies, René and Hölzer, Martin and Brizola Toscan, Rodolfo and Nunes da Rocha, Ulisses and Anders, John and Marz, Manja and Chatzinotas, Antonis},
    title = {Evaluation of Sequencing Library Preparation Protocols for Viral Metagenomic Analysis from Pristine Aquifer Groundwaters.},
    journal = {Viruses},
    year = {2019},
    volume = {11},
    abstract = {Viral ecology of terrestrial habitats is yet-to be extensively explored, in particular the terrestrial subsurface. One problem in obtaining viral sequences from groundwater aquifer samples is the relatively low amount of virus particles. As a result, the amount of extracted DNA may not be sufficient for direct sequencing of such samples. Here we compared three DNA amplification methods to enrich viral DNA from three pristine limestone aquifer assemblages of the Hainich Critical Zone Exploratory to evaluate potential bias created by the different amplification methods as determined by viral metagenomics. Linker amplification shotgun libraries resulted in lowest redundancy among the sequencing reads and showed the highest diversity, while multiple displacement amplification produced the highest number of contigs with the longest average contig size, suggesting a combination of these two methods is suitable for the successful enrichment of viral DNA from pristine groundwater samples. In total, we identified 27,173, 5,886 and 32,613 viral contigs from the three samples from which 11.92 to 18.65% could be assigned to taxonomy using blast. Among these, members of the order were the most abundant group (52.20 to 69.12%) dominated by and . Those, and the high number of unknown viral sequences, substantially expand the known virosphere.},
    doi = {10.3390/v11060484},
    issue = {6},
    keywords = {AquaDiva; aquifer; groundwater; sequencing library preparation; viral metagenome},
    pmid = {31141902},
    }
  • [DOI] A. Dukhovny, K. Lamkiewicz, Q. Chen, M. Fricke, N. Jabrane-Ferrat, M. Marz, J. U. Jung, and E. H. Sklan, “A CRISPR activation screen identifies genes protecting from Zika virus infection,” J Virol, 2019.
    [Bibtex]
    @Article{Dukhovny:19,
    author = {Dukhovny, Anna and Lamkiewicz, Kevin and Chen, Qian and Fricke, Markus and Jabrane-Ferrat, Nabila and Marz, Manja and Jung, Jae U. and Sklan, Ella H.},
    title = {A {CRISPR} activation screen identifies genes protecting from {Z}ika virus infection},
    journal = {{J Virol}},
    year = {2019},
    abstract = {Zika virus (ZIKV) is an arthropod borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barr{\'e} syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection we used a genome scale CRISPR activation screen. Our highly ranking hits included a short list of interferon stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted IFNL2 and IFI6 as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing sgRNAs for both of these genes displayed lower levels of cell death compared to controls. Furthermore, the identified genes were significantly induced in ZIKV infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiates CRISPR activation screens as a tool to identify host factors impeding pathogen infection.IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barr{\'e} syndrome, neuropathy and myelitis. Vertical transmission of ZIKV can cause fetus demise, still birth or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.},
    doi = {10.1128/JVI.00211-19},
    elocation-id = {JVI.00211-19},
    eprint = {https://jvi.asm.org/content/early/2019/05/23/JVI.00211-19.full.pdf},
    publisher = {American Society for Microbiology Journals},
    url = {https://jvi.asm.org/content/early/2019/05/23/JVI.00211-19},
    }
  • [DOI] M. Hölzer, A. Schoen, J. Wulle, M. A. Müller, C. Drosten, M. Marz, and F. Weber, “Virus- and interferon alpha-induced transcriptomes of cells from the microbat Myotis daubentonii,” iScience, vol. 19, pp. 647-661, 2019.
    [Bibtex]
    @Article{Hölzer:19a,
    author = {Martin Hölzer and Andreas Schoen and Julia Wulle and Marcel A. Müller and Christian Drosten and Manja Marz and Friedemann Weber},
    title = {Virus- and interferon alpha-induced transcriptomes of cells from the microbat {Myotis daubentonii}},
    journal = {{iScience}},
    year = {2019},
    volume = {19},
    pages = {647-661},
    doi = {10.1016/j.isci.2019.08.016},
    publisher = {Elsevier {BV}},
    }
  • [DOI] D. M. Morales-Prieto, E. Barth, J. M. Murrieta-Coxca, R. R. Favaro, R. N. Gutiérrez-Samudio, W. Chaiwangyen, S. Ospina-Prieto, B. Gruhn, E. Schleußner, M. Marz, and U. R. Markert, “Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines.,” Placenta, vol. 88, p. 20–27, 2019.
    [Bibtex]
    @Article{Morales-Prieto:19,
    author = {Morales-Prieto, Diana M and Barth, Emanuel and Murrieta-Coxca, Jose Martín and Favaro, Rodolfo R and Gutiérrez-Samudio, Ruby N and Chaiwangyen, Wittaya and Ospina-Prieto, Stephanie and Gruhn, Bernd and Schleußner, Ekkehard and Marz, Manja and Markert, Udo R},
    title = {Identification of {miRNAs} and associated pathways regulated by {L}eukemia {I}nhibitory {F}actor in trophoblastic cell lines.},
    journal = {Placenta},
    year = {2019},
    volume = {88},
    pages = {20--27},
    abstract = {Leukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways. Low density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR. A similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target. Dissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.},
    doi = {10.1016/j.placenta.2019.09.005},
    keywords = {Cell lines; LIF; Placenta; Pregnancy; Trophoblast; miR-21; microRNA},
    pmid = {31586768},
    }
  • [DOI] E. Barth, A. Srivastava, M. Stojiljkovic, C. Frahm, H. Axer, O. W. Witte, and M. Marz, “Conserved aging-related signatures of senescence and inflammation in different tissues and species.,” Aging, vol. 11, 2019.
    [Bibtex]
    @Article{Barth:19,
    author = {Barth, Emanuel and Srivastava, Akash and Stojiljkovic, Milan and Frahm, Christiane and Axer, Hubertus and Witte, Otto W and Marz, Manja},
    title = {Conserved aging-related signatures of senescence and inflammation in different tissues and species.},
    journal = {Aging},
    year = {2019},
    volume = {11},
    abstract = {Increasing evidence indicates that chronic inflammation and senescence are the cause of many severe age-related diseases, with both biological processes highly upregulated during aging. However, until now, it has remained unknown whether specific inflammation- or senescence-related genes exist that are common between different species or tissues. These potential markers of aging could help to identify possible targets for therapeutic interventions of aging-associated afflictions and might also deepen our understanding of the principal mechanisms of aging. With the objective of identifying such signatures of aging and tissue-specific aging markers, we analyzed a multitude of cross-sectional RNA-Seq data from four evolutionarily distinct species (human, mouse and two fish) and four different tissues (blood, brain, liver and skin). In at least three different species and three different tissues, we identified several genes that displayed similar expression patterns that might serve as potential aging markers. Additionally, we show that genes involved in aging-related processes tend to be tighter controlled in long-lived than in average-lived individuals. These observations hint at a general genetic level that affect an individual's life span. Altogether, this descriptive study contributes to a better understanding of common aging signatures as well as tissue-specific aging patterns and supplies the basis for further investigative age-related studies.},
    doi = {10.18632/aging.102345},
    keywords = {RNA-Seq; aging; inflammaging; senescence; transcriptomics},
    pmid = {31606727},
    }
  • [DOI] N. F. Mostajo, M. Lataretu, S. Krautwurst, F. Mock, D. Desirò, K. Lamkiewicz, M. Collatz, A. Schoen, F. Weber, M. Marz, and M. Hölzer, “A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes,” Nar genomics and bioinformatics, vol. 2, iss. 1, 2019.
    [Bibtex]
    @article{Mostajo:19,
    author = {Mostajo, Nelly F and Lataretu, Marie and Krautwurst, Sebastian and Mock, Florian and Desirò, Daniel and Lamkiewicz, Kevin and Collatz, Maximilian and Schoen, Andreas and Weber, Friedemann and Marz, Manja and H\"{o}lzer, Martin},
    title = "{A comprehensive annotation and differential expression analysis of short and long non-coding {R}{N}{A}s in 16 bat genomes}",
    journal = {NAR Genomics and Bioinformatics},
    volume = {2},
    number = {1},
    year = {2019},
    month = {09},
    issn = {2631-9268},
    doi = {10.1093/nargab/lqz006},
    url = {https://doi.org/10.1093/nargab/lqz006},
    note = {lqz006},
    eprint = {http://oup.prod.sis.lan/nargab/article-pdf/2/1/lqz006/30076191/lqz006.pdf},
    }

2018

  • [DOI] M. Fricke, R. Gerst, B. Ibrahim, M. Niepmann, and M. Marz, “Global importance of RNA secondary structures in protein coding sequences,” Bioinformatics, 2018.
    [Bibtex]
    @Article{Fricke:18,
    author = {Fricke, Markus and Gerst, Ruman and Ibrahim, Bashar and Niepmann, Michael and Marz, Manja},
    title = {Global importance of {RNA} secondary structures in protein coding sequences},
    journal = {Bioinformatics},
    year = {2018},
    abstract = {The protein-coding sequences of messenger RNAs are the linear template for translation of the gene sequence into protein. Nevertheless, the RNA can also form secondary structures by intramolecular base-pairing. We show that the nucleotide distribution within codons is biased in all taxa of life on a global scale. Thereby, RNA secondary structures that require base-pairing between the position 1 of a codon with the position 1 of an opposing codon (here named RNA secondary structure class c1) are under-represented. We conclude that this bias may result from the co-evolution of codon sequence and mRNA secondary structure, suggesting that RNA secondary structures are generally important in protein coding regions of mRNAs. The above result also implies that codon position 2 has a smaller influence on the amino acid choice than codon position 1.},
    doi = {10.1093/bioinformatics/bty678},
    pmid = {30101307},
    }
  • [DOI] B. Ibrahim, K. Arkhipova, A. C. Andeweg, S. Posada-Céspedes, F. Enault, A. Gruber, E. V. Koonin, A. Kupczok, P. Lemey, A. C. McHardy, D. P. McMahon, B. E. Pickett, D. L. Robertson, R. H. Scheuermann, A. Zhernakova, M. P. Zwart, A. Schönhuth, B. E. Dutilh, and M. Marz, “Bioinformatics meets virology: the European Virus Bioinformatics Center’s second annual meeting,” Viruses, vol. 10, 2018.
    [Bibtex]
    @Article{Ibrahim:18,
    author = {Ibrahim, Bashar and Arkhipova, Ksenia and Andeweg, Arno C and Posada-C\'{e}spedes, Susana and Enault, Fran\c{c}ois and Gruber, Arthur and Koonin, Eugene V and Kupczok, Anne and Lemey, Philippe and McHardy, Alice C and McMahon, Dino P and Pickett, Brett E and Robertson, David L and Scheuermann, Richard H and Zhernakova, Alexandra and Zwart, Mark P and Sch\"{o}nhuth, Alexander and Dutilh, Bas E and Marz, Manja},
    title = {Bioinformatics Meets Virology: The {E}uropean {V}irus {B}ioinformatics {C}enter's Second Annual Meeting},
    journal = {{Viruses}},
    year = {2018},
    volume = {10},
    abstract = {The Second Annual Meeting of the European Virus Bioinformatics Center (EVBC), held in Utrecht, Netherlands, focused on computational approaches in virology, with topics including (but not limited to) virus discovery, diagnostics, (meta-)genomics, modeling, epidemiology, molecular structure, evolution, and viral ecology. The goals of the Second Annual Meeting were threefold: (i) to bring together virologists and bioinformaticians from across the academic, industrial, professional, and training sectors to share best practice; (ii) to provide a meaningful and interactive scientific environment to promote discussion and collaboration between students, postdoctoral fellows, and both new and established investigators; (iii) to inspire and suggest new research directions and questions. Approximately 120 researchers from around the world attended the Second Annual Meeting of the EVBC this year, including 15 renowned international speakers. This report presents an overview of new developments and novel research findings that emerged during the meeting.},
    doi = {10.3390/v10050256},
    issue = {5},
    keywords = {bioinformatics; software; virology; viruses},
    pmid = {29757994},
    }
  • [DOI] B. Ibrahim, D. P. McMahon, F. Hufsky, M. Beer, L. Deng, P. L. Mercier, M. Palmarini, V. Thiel, and M. Marz, “A new era of virus bioinformatics,” Virus Res, vol. 251, p. 86–90, 2018.
    [Bibtex]
    @Article{Ibrahim:18a,
    author = {Ibrahim, Bashar and McMahon, Dino P and Hufsky, Franziska and Beer, Martin and Deng, Li and Mercier, Philippe Le and Palmarini, Massimo and Thiel, Volker and Marz, Manja},
    title = {A new era of virus bioinformatics},
    journal = {{Virus Res}},
    year = {2018},
    volume = {251},
    pages = {86--90},
    abstract = {Despite the recognized excellence of virology and bioinformatics, these two communities have interacted surprisingly sporadically, aside from some pioneering work on HIV-1 and influenza. Bringing together the expertise of bioinformaticians and virologists is crucial, since very specific but fundamental computational approaches are required for virus research, particularly in an era of big data. Collaboration between virologists and bioinformaticians is necessary to improve existing analytical tools, cloud-based systems, computational resources, data sharing approaches, new diagnostic tools, and bioinformatic training. Here, we highlight current progress and discuss potential avenues for future developments in this promising era of virus bioinformatics. We end by presenting an overview of current technologies, and by outlining some of the major challenges and advantages that bioinformatics will bring to the field of virology.},
    doi = {10.1016/j.virusres.2018.05.009},
    keywords = {Computational Biology, methods, trends; Virology, methods, trends; Viruses, genetics, growth & development; Bioinformatics; Software; Virology; Viruses},
    pmid = {29751021},
    }
  • D. Steinbach, M. Hölzer, M. Marz, M. Gajda, F-C. Von Rundstedt, and M-O. Grimm, “Analysis of molecular mechanism of progression of non-muscle-invasive bladder cancer (NMIBC) by genome-wide exome and UTR mutation analysis,” Eur Urol Suppl, vol. 17, iss. 2, p. e1523, 2018.
    [Bibtex]
    @Article{Steinbach:18,
    author = {Steinbach, D and H{\"o}lzer, M and Marz, M and Gajda, M and Von Rundstedt, F-C and Grimm, M-O},
    title = {Analysis of molecular mechanism of progression of non-muscle-invasive bladder cancer ({NMIBC}) by genome-wide exome and {UTR} mutation analysis},
    journal = {{Eur Urol Suppl}},
    year = {2018},
    volume = {17},
    number = {2},
    pages = {e1523},
    publisher = {Elsevier},
    }
  • [DOI] F. Hillmann, G. Forbes, S. Novohradská, I. Ferling, K. Riege, M. Groth, M. Westermann, M. Marz, T. Spaller, T. Winckler, P. Schaap, and G. Glöckner, “Multiple roots of fruiting body formation in amoebozoa,” Genome Biol Evol, vol. 10, p. 591–606, 2018.
    [Bibtex]
    @Article{Hillmann:18,
    author = {Hillmann, Falk and Forbes, Gillian and Novohradsk\'{a}, Silvia and Ferling, Iuliia and Riege, Konstantin and Groth, Marco and Westermann, Martin and Marz, Manja and Spaller, Thomas and Winckler, Thomas and Schaap, Pauline and Gl\"{o}ckner, Gernot},
    title = {Multiple Roots of Fruiting Body Formation in Amoebozoa},
    journal = {{Genome Biol Evol}},
    year = {2018},
    volume = {10},
    pages = {591--606},
    abstract = {Establishment of multicellularity represents a major transition in eukaryote evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively simple aggregative multicellular stage resulting in a fruiting body supported by a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree, differ by producing only one or few single stalked spores. Thus, one obvious difference in the developmental cycle of protosteliids and dictyosteliids seems to be the establishment of multicellularity. To separate spore development from multicellular interactions, we compared the genome and transcriptome of a Protostelium species (Protostelium aurantium var. fungivorum) with those of social and solitary members of the Amoebozoa. During fruiting body formation nearly 4,000 genes, corresponding to specific pathways required for differentiation processes, are upregulated. A comparison with genes involved in the development of dictyosteliids revealed conservation of >500 genes, but most of them are also present in Acanthamoeba castellanii for which fruiting bodies have not been documented. Moreover, expression regulation of those genes differs between P. aurantium and Dictyostelium discoideum. Within Amoebozoa differentiation to fruiting bodies is common, but our current genome analysis suggests that protosteliids and dictyosteliids used different routes to achieve this. Most remarkable is both the large repertoire and diversity between species in genes that mediate environmental sensing and signal processing. This likely reflects an immense adaptability of the single cell stage to varying environmental conditions. We surmise that this signaling repertoire provided sufficient building blocks to accommodate the relatively simple demands for cell-cell communication in the early multicellular forms.},
    doi = {10.1093/gbe/evy011},
    issue = {2},
    keywords = {Amoebozoa, cytology, genetics, growth & development; Cell Communication; Dictyostelium, cytology, genetics, growth & development; Evolution, Molecular; Gene Expression Regulation, Developmental; Phylogeny; Protozoan Proteins, genetics; Transcriptome; Amoebozoa; Dictyostelia; Protostelium; evolution of development; multicellular development; signaling; transcriptome},
    pmid = {29378020},
    }
  • [DOI] F. Hufsky, B. Ibrahim, M. Beer, L. Deng, P. L. Mercier, D. P. McMahon, M. Palmarini, V. Thiel, and M. Marz, “Virologists-heroes need weapons,” PLoS Pathog, vol. 14, p. e1006771, 2018.
    [Bibtex]
    @Article{Hufsky:18,
    author = {Hufsky, Franziska and Ibrahim, Bashar and Beer, Martin and Deng, Li and Mercier, Philippe Le and McMahon, Dino P and Palmarini, Massimo and Thiel, Volker and Marz, Manja},
    title = {Virologists-Heroes need weapons},
    journal = {{PLoS Pathog}},
    year = {2018},
    volume = {14},
    pages = {e1006771},
    doi = {10.1371/journal.ppat.1006771},
    issue = {2},
    keywords = {Animals; Biomedical Research, manpower, methods, trends; Computational Biology, manpower, methods, trends; Europe; Humans; Professional Role; Virology, manpower, methods, trends},
    pmid = {29420617},
    }
  • [DOI] L. Graf, A. Dick, F. Sendker, E. Barth, M. Marz, O. Daumke, and G. Kochs, “Effects of allelic variations in the human myxovirus resistance protein A on its antiviral activity,” J Biol Chem, vol. 293, p. 3056–3072, 2018.
    [Bibtex]
    @Article{Graf:18,
    author = {Graf, Laura and Dick, Alexej and Sendker, Franziska and Barth, Emanuel and Marz, Manja and Daumke, Oliver and Kochs, Georg},
    title = {Effects of allelic variations in the human myxovirus resistance protein {A} on its antiviral activity},
    journal = {{J Biol Chem}},
    year = {2018},
    volume = {293},
    pages = {3056--3072},
    abstract = {Only a minority of patients infected with seasonal influenza A viruses exhibit a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 ( ) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition. We used online databases to search for variations in the gene. Deploying approaches, we found that non-synonymous variations in the GTPase domain cause the loss of antiviral and enzymatic activities. Furthermore, we showed that these amino acid substitutions disrupt the interface for GTPase domain dimerization required for the stimulation of GTP hydrolysis. Variations in the stalk were neutral or slightly enhanced or abolished MxA antiviral function. Remarkably, two other stalk variants altered MxA's antiviral specificity. Variations causing the loss of antiviral activity were found only in heterozygous carriers. Interestingly, the inactive stalk variants blocked the antiviral activity of WT MxA in a dominant-negative way, suggesting that heterozygotes are phenotypically MxA-negative. In contrast, the GTPase-deficient variants showed no dominant-negative effect, indicating that heterozygous carriers should remain unaffected. Our results demonstrate that naturally occurring mutations in the human gene can influence MxA function, which may explain individual variations in influenza virus susceptibility in the human population.},
    doi = {10.1074/jbc.M117.812784},
    issue = {9},
    keywords = {Mx proteins; allelic variations; antiviral response; dynamin; genetic polymorphism; influenza virus; innate immunity; interferon},
    pmid = {29330299},
    }
  • [DOI] R. Madhugiri, N. Karl, D. Petersen, K. Lamkiewicz, M. Fricke, U. Wend, R. Scheuer, M. Marz, and J. Ziebuhr, “Structural and functional conservation of cis-acting RNA elements in coronavirus 5′-terminal genome regions,” Virology, vol. 517, p. 44–55, 2018.
    [Bibtex]
    @Article{Madhugiri:18,
    author = {Madhugiri, Ramakanth and Karl, Nadja and Petersen, Daniel and Lamkiewicz, Kevin and Fricke, Markus and Wend, Ulrike and Scheuer, Robina and Marz, Manja and Ziebuhr, John},
    title = {Structural and functional conservation of cis-acting {RNA} elements in coronavirus 5'-terminal genome regions},
    journal = {{Virology}},
    year = {2018},
    volume = {517},
    pages = {44--55},
    abstract = {Structure predictions suggest a partial conservation of RNA structure elements in coronavirus terminal genome regions. Here, we determined the structures of stem-loops (SL) 1 and 2 of two alphacoronaviruses, human coronavirus (HCoV) 229E and NL63, by RNA structure probing and studied the functional relevance of these putative cis-acting elements. HCoV-229E SL1 and SL2 mutants generated by reverse genetics were used to study the effects on viral replication of single-nucleotide substitutions predicted to destabilize the SL1 and SL2 structures. The data provide conclusive evidence for the critical role of SL1 and SL2 in HCoV-229E replication and, in some cases, revealed parallels with previously characterized betacoronavirus SL1 and SL2 elements. Also, we were able to rescue viable HCoV-229E mutants carrying replacements of SL2 with equivalent betacoronavirus structural elements. The data obtained in this study reveal a remarkable degree of structural and functional conservation of 5'-terminal RNA structural elements across coronavirus genus boundaries.},
    doi = {10.1016/j.virol.2017.11.025},
    keywords = {Base Sequence; Cell Line; Coronavirus 229E, Human, genetics; Coronavirus NL63, Human, genetics; Genome, Viral; Humans; Nucleic Acid Conformation; RNA, Viral, chemistry, genetics; Regulatory Sequences, Nucleic Acid, physiology; Virus Replication, physiology; Coronavirus; Coronavirus phylogeny; RNA structure; Replication; Stem-loop; cis-acting RNA element},
    pmid = {29223446},
    }
  • [DOI] T. Marschall, M. Marz, T. Abeel, L. Dijkstra, B. E. Dutilh, A. Ghaffaari, P. Kersey, W. P. Kloosterman, V. Mäkinen, A. M. Novak, B. Paten, D. Porubsky, E. Rivals, C. Alkan, J. A. Baaijens, P. I. W. De Bakker, V. Boeva, R. J. P. Bonnal, F. Chiaromonte, R. Chikhi, F. D. Ciccarelli, R. Cijvat, E. Datema, C. M. Van Duijn, E. E. Eichler, C. Ernst, E. Eskin, E. Garrison, M. El-Kebir, G. W. Klau, J. O. Korbel, E. Lameijer, B. Langmead, M. Martin, P. Medvedev, J. C. Mu, P. Neerincx, K. Ouwens, P. Peterlongo, N. Pisanti, S. Rahmann, B. Raphael, K. Reinert, D. de Ridder, J. de Ridder, M. Schlesner, O. Schulz-Trieglaff, A. D. Sanders, S. Sheikhizadeh, C. Shneider, S. Smit, D. Valenzuela, J. Wang, L. Wessels, Y. Zhang, V. Guryev, F. Vandin, K. Ye, and A. Schönhuth, “Computational pan-genomics: status, promises and challenges,” Briefings Bioinf, vol. 19, p. 118–135, 2018.
    [Bibtex]
    @Article{Consortium:18,
    author = {Marschall, Tobias and Marz, Manja and Abeel, Thomas and Dijkstra, Louis and Dutilh, Bas E and Ghaffaari, Ali and Kersey, Paul and Kloosterman, Wigard P and M\"{a}kinen, Veli and Novak, Adam M and Paten, Benedict and Porubsky, David and Rivals, Eric and Alkan, Can and Baaijens, Jasmijn A and De Bakker, Paul I W and Boeva, Valentina and Bonnal, Raoul J P and Chiaromonte, Francesca and Chikhi, Rayan and Ciccarelli, Francesca D and Cijvat, Robin and Datema, Erwin and Van Duijn, Cornelia M and Eichler, Evan E and Ernst, Corinna and Eskin, Eleazar and Garrison, Erik and El-Kebir, Mohammed and Klau, Gunnar W and Korbel, Jan O and Lameijer, Eric-Wubbo and Langmead, Benjamin and Martin, Marcel and Medvedev, Paul and Mu, John C and Neerincx, Pieter and Ouwens, Klaasjan and Peterlongo, Pierre and Pisanti, Nadia and Rahmann, Sven and Raphael, Ben and Reinert, Knut and de Ridder, Dick and de Ridder, Jeroen and Schlesner, Matthias and Schulz-Trieglaff, Ole and Sanders, Ashley D and Sheikhizadeh, Siavash and Shneider, Carl and Smit, Sandra and Valenzuela, Daniel and Wang, Jiayin and Wessels, Lodewyk and Zhang, Ying and Guryev, Victor and Vandin, Fabio and Ye, Kai and Sch\"{o}nhuth, Alexander},
    title = {Computational pan-genomics: status, promises and challenges},
    journal = {{Briefings Bioinf}},
    year = {2018},
    volume = {19},
    pages = {118--135},
    abstract = {Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.},
    doi = {10.1093/bib/bbw089},
    issue = {1},
    keywords = {Algorithms; Computational Biology, methods; Genome, Human; Genomics, methods; Humans; Software; data structures; haplotypes; pan-genome; read mapping; sequence graph},
    pmid = {27769991},
    }
  • [DOI] D. Desiro, M. Hölzer, B. Ibrahim, and M. Marz, “SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structured RNAs,” Virus Res, 2018.
    [Bibtex]
    @Article{Desiro:18,
    author = {Desiro, Daniel and H\"{o}lzer, Martin and Ibrahim, Bashar and Marz, Manja},
    title = {{SilentMutations} ({SIM}): a tool for analyzing long-range {RNA-RNA} interactions in viral genomes and structured {RNA}s},
    journal = {{Virus Res}},
    year = {2018},
    abstract = {A single nucleotide change in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication. In recent decades, several tools have been developed to predict the effect of mutations in structured RNAs such as viral genomes or non-coding RNAs. Some tools use multiple point mutations and also take coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions. Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate disruptive and compensatory mutants of two interacting single-stranded RNAs. This allows a fast and accurate assessment of key regions potentially involved in functional long-range RNA-RNA interactions and will eventually help virologists and RNA-experts to design appropriate experiments. SIM only requires two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions. We applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments. The source code and documentation of SIM are freely available at github.com/desiro/silentMutations.},
    doi = {10.1016/j.virusres.2018.11.005},
    keywords = {Codon Mutation; Double-mutant; RNA secondary structure; RNA virus; Virology; Virus Bioinformatics; silent mutation},
    pmid = {30439394},
    }
  • [DOI] K. Lamkiewicz, E. Barth, M. Marz, and B. Ibrahim, “Identification of potential microRNAs associated with Herpesvirus family based on bioinformatic analysis,” bioRxiv, p. 417782, 2018.
    [Bibtex]
    @Article{Lamkiewicz:18,
    author = {Kevin Lamkiewicz and Emanuel Barth and Manja Marz and Bashar Ibrahim},
    title = {Identification of potential {microRNAs} associated with {H}erpesvirus family based on bioinformatic analysis},
    journal = {{bioRxiv}},
    year = {2018},
    pages = {417782},
    doi = {10.1101/417782},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] D. M. Morales-Prieto, E. Barth, R. N. Gutièrrez-Samudio, W. Chaiwangyen, S. Ospina-Prieto, B. Gruhn, E. Schleußner, M. Marz, and U. R. Markert, “Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines,” bioRxiv, p. 410381, 2018.
    [Bibtex]
    @Article{Morales-Prieto:18,
    author = {Diana M. Morales-Prieto and Emanuel Barth and Ruby N. Guti{\`{e}}rrez-Samudio and Wittaya Chaiwangyen and Stephanie Ospina-Prieto and Bernd Gruhn and Ekkehard Schleu{\ss}ner and Manja Marz and Udo R. Markert},
    title = {Identification of {miRNAs} and associated pathways regulated by {L}eukemia {I}nhibitory {F}actor in trophoblastic cell lines},
    journal = {{bioRxiv}},
    year = {2018},
    pages = {410381},
    doi = {10.1101/410381},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] Z. Chen, E. M. Amro, F. Becker, M. Hölzer, S. M. M. Rasa, S. N. Njeru, B. Han, S. D. Sanzo, Y. Chen, D. Tang, S. Tao, R. Haenold, M. Groth, V. S. Romanov, J. M. Kirkpatrick, J. M. Kraus, H. A. Kestler, M. Marz, A. Ori, F. Neri, Y. Morita, and L. K. Rudolph, “Cohesin-mediated NF-Κb signaling limits hematopoietic stem cell self-renewal in aging and inflammation,” J Exp Med, vol. 216, iss. 1, p. 152–175, 2018.
    [Bibtex]
    @Article{Chen:18,
    author = {Zhiyang Chen and Elias Moris Amro and Friedrich Becker and Martin H\"{o}lzer and Seyed Mohammad Mahdi Rasa and Sospeter Ngoci Njeru and Bing Han and Simone Di Sanzo and Yulin Chen and Duozhuang Tang and Si Tao and Ronny Haenold and Marco Groth and Vasily S. Romanov and Joanna M. Kirkpatrick and Johann M. Kraus and Hans A. Kestler and Manja Marz and Alessandro Ori and Francesco Neri and Yohei Morita and K. Lenhard Rudolph},
    title = {Cohesin-mediated {NF}-\ΚB signaling limits hematopoietic stem cell self-renewal in aging and inflammation},
    journal = {{J Exp Med}},
    year = {2018},
    volume = {216},
    number = {1},
    pages = {152--175},
    doi = {10.1084/jem.20181505},
    publisher = {Rockefeller University Press},
    }
  • [DOI] R. Gerst and M. Hölzer, “PCAGO: an interactive web service to analyze RNA-seq data with principal component analysis,” bioRxiv, p. 433078, 2018.
    [Bibtex]
    @Article{Gerst:18,
    author = {Ruman Gerst and Martin H\"{o}lzer},
    title = {{PCAGO}: An interactive web service to analyze {RNA}-Seq data with principal component analysis},
    journal = {{bioRxiv}},
    year = {2018},
    pages = {433078},
    doi = {10.1101/433078},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] D. M. Morales-Prieto, M. Stojiljkovic, C. Diezel, P. Streicher, F. Roestel, J. Lindner, S. Weis, C. Schmeer, and M. Marz, “Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation,” bioRxiv, p. 471409, 2018.
    [Bibtex]
    @Article{Morales-Prieto:18a,
    author = {Diana M. Morales-Prieto and Milan Stojiljkovic and Celia Diezel and Priska-Elisabeth Streicher and Franziska Roestel and Julia Lindner and Sebastian Weis and Christian Schmeer and Manja Marz},
    title = {Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation},
    journal = {{bioRxiv}},
    year = {2018},
    pages = {471409},
    doi = {10.1101/471409},
    publisher = {Cold Spring Harbor Laboratory},
    }

2017

  • [DOI] M. Baumgart, E. Barth, A. Savino, M. Groth, P. Koch, A. Petzold, I. Arisi, M. Platzer, M. Marz, and A. Cellerino, “A miRNA catalogue and ncRNA annotation of the short-living fish Nothobranchius furzeri,” BMC Genomics, vol. 18, p. 693, 2017.
    [Bibtex]
    @Article{Baumgart:17,
    author = {Baumgart, Mario and Barth, Emanuel and Savino, Aurora and Groth, Marco and Koch, Philipp and Petzold, Andreas and Arisi, Ivan and Platzer, Matthias and Marz, Manja and Cellerino, Alessandro},
    title = {A mi{RNA} catalogue and nc{RNA} annotation of the short-living fish {N}othobranchius furzeri},
    journal = {{BMC Genomics}},
    year = {2017},
    volume = {18},
    pages = {693},
    abstract = {The short-lived fish Nothobranchius furzeri is the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age dependent control of gene expression. Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) for Nothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of seven Nothobranchius species. Additionally, duplication and clustering of N. furzeri miRNAs was analyzed and compared to the four fish species Danio rerio, Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes. A peculiar characteristic of N. furzeri, as compared to other teleosts, was a duplication of the miR-29 cluster. The completeness of the catalogue we provide is comparable to that of the zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.},
    doi = {10.1186/s12864-017-3951-8},
    issue = {1},
    keywords = {Aging, genetics; Animals; Cyprinodontiformes, genetics, physiology; Gene Duplication; Gene Library; Longevity, genetics; MicroRNAs, genetics; Molecular Sequence Annotation; RNA, Untranslated, genetics; Fish miRNA evolution; Nothobranchius furzeri; miRNome; ncRNA},
    pmid = {28874118},
    }
  • [DOI] P. Möbius, G. Nordsiek, M. Hölzer, M. Jarek, M. Marz, and H. Köhler, “Complete genome sequence of JII-1961, a bovine Mycobacterium avium subsp. paratuberculosis field isolate from Germany,” Genome Announc, vol. 5, 2017.
    [Bibtex]
    @Article{Moebius:17,
    author = {M\"{o}bius, Petra and Nordsiek, Gabriele and H\"{o}lzer, Martin and Jarek, Michael and Marz, Manja and K\"{o}hler, Heike},
    title = {Complete Genome Sequence of {JII}-1961, a Bovine {M}ycobacterium avium subsp. paratuberculosis Field Isolate from {G}ermany},
    journal = {{Genome Announc}},
    year = {2017},
    volume = {5},
    abstract = { subsp. causes Johne's disease in ruminants and was also detected in nonruminant species, including human beings, and in milk products. We announce here the 4.829-Mb complete genome sequence of the cattle-type strain JII-1961 from Germany, which is very similar to cattle-type strains recovered from different continents.},
    doi = {10.1128/genomeA.00870-17},
    issue = {34},
    pmid = {28839035},
    }
  • W. Chaiwangyen, R. N. Gutiérrez-Samudio, U. R. Markert, M. Marz, D. M. Morales-Prieto, and S. Ospina-Prieto, “KL 5 Trophoblast-immune cell communication via microRNA transported in extracellular vesicles,” Pregnancy Hypertens, vol. 9, p. 5, 2017.
    [Bibtex]
    @Article{Chaiwangyen:17,
    author = {Chaiwangyen, Wittaya and Guti{\'e}rrez-Samudio, Ruby N and Markert, Udo R and Marz, Manja and Morales-Prieto, Diana M and Ospina-Prieto, Stephanie},
    title = {{KL} 5 {T}rophoblast-immune cell communication via micro{RNA} transported in extracellular vesicles},
    journal = {{Pregnancy Hypertens}},
    year = {2017},
    volume = {9},
    pages = {5},
    publisher = {Elsevier},
    }
  • [DOI] J. Fuchs, M. Hölzer, M. Schilling, C. Patzina, A. Schoen, T. Hoenen, G. Zimmer, M. Marz, F. Weber, M. A. Müller, and G. Kochs, “Evolution and antiviral specificities of interferon-induced Mx proteins of bats against Ebola, Influenza, and other RNA viruses,” J Virol, vol. 91, 2017.
    [Bibtex]
    @Article{Fuchs:17,
    author = {Fuchs, Jonas and H\"{o}lzer, Martin and Schilling, Mirjam and Patzina, Corinna and Schoen, Andreas and Hoenen, Thomas and Zimmer, Gert and Marz, Manja and Weber, Friedemann and M\"{u}ller, Marcel A and Kochs, Georg},
    title = {Evolution and Antiviral Specificities of Interferon-Induced {Mx} Proteins of Bats against {E}bola, {I}nfluenza, and Other {RNA} Viruses},
    journal = {{J Virol}},
    year = {2017},
    volume = {91},
    abstract = {Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed. To provide evidence that bat Mx proteins might act as key factors to control viral replication we cloned cDNAs from three bat families, Pteropodidae, Phyllostomidae, and Vespertilionidae. Phylogenetically these bat genes cluster closely with their human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus-like particles, and virus infections, we determined the antiviral potential of the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of viruses circulating in bats, including Ebola and influenza A-like viruses. The related Thogoto virus, however, which is not known to infect bats, was not inhibited by bat Mx1. Further, we provide evidence for positive selection in bat genes that might explain species-specific antiviral activities of these proteins. Together, our data suggest a role for Mx1 in controlling these viruses in their bat hosts. Bats are a natural reservoir for various viruses that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens, like Ebola or rabies virus. It has been hypothesized that the interferon system might play a key role in controlling viral replication in bats. We speculate that the interferon-induced Mx proteins might be key antiviral factors of bats and have coevolved with bat-borne viruses. This study evaluated for the first time a large set of bat Mx1 proteins spanning three major bat families for their antiviral potential, including activity against Ebola virus and bat influenza A-like virus, and we describe here their phylogenetic relationship, revealing patterns of positive selection that suggest a coevolution with viral pathogens. By understanding the molecular mechanisms of the innate resistance of bats against viral diseases, we might gain important insights into how to prevent and fight human zoonotic infections caused by bat-borne viruses.},
    doi = {10.1128/JVI.00361-17},
    issue = {15},
    keywords = {Animals; Antiviral Agents, metabolism; Chiroptera, immunology, virology; Cloning, Molecular; Evolution, Molecular; Myxovirus Resistance Proteins, genetics, metabolism; RNA Viruses, immunology; Selection, Genetic; Ebola virus; Mx protein; bat; bunyavirus; influenza; interferons; orthomyxovirus; vesicular stomatitis virus},
    pmid = {28490593},
    }
  • [DOI] K. Riege, M. Hölzer, T. E. Klassert, E. Barth, J. Bräuer, M. Collatz, F. Hufsky, N. Mostajo, M. Stock, B. Vogel, H. Slevogt, and M. Marz, “Massive effect on lncRNAs in human monocytes during fungal and bacterial infections and in response to vitamins A and D,” Sci Rep, vol. 7, p. 40598, 2017.
    [Bibtex]
    @Article{Riege:17,
    author = {Riege, Konstantin and H\"{o}lzer, Martin and Klassert, Tilman E and Barth, Emanuel and Br\"{a}uer, Julia and Collatz, Maximilian and Hufsky, Franziska and Mostajo, Nelly and Stock, Magdalena and Vogel, Bertram and Slevogt, Hortense and Marz, Manja},
    title = {Massive Effect on Lnc{RNA}s in Human Monocytes During Fungal and Bacterial Infections and in Response to Vitamins {A} and {D}},
    journal = {{Sci Rep}},
    year = {2017},
    volume = {7},
    pages = {40598},
    abstract = {Mycoses induced by C.albicans or A.fumigatus can cause important host damage either by deficient or exaggerated immune response. Regulation of chemokine and cytokine signaling plays a crucial role for an adequate inflammation, which can be modulated by vitamins A and D. Non-coding RNAs (ncRNAs) as transcription factors or cis-acting antisense RNAs are known to be involved in gene regulation. However, the processes during fungal infections and treatment with vitamins in terms of therapeutic impact are unknown. We show that in monocytes both vitamins regulate ncRNAs involved in amino acid metabolism and immune system processes using comprehensive RNA-Seq analyses. Compared to protein-coding genes, fungi and bacteria induced an expression change in relatively few ncRNAs, but with massive fold changes of up to 4000. We defined the landscape of long-ncRNAs (lncRNAs) in response to pathogens and observed variation in the isoforms composition for several lncRNA following infection and vitamin treatment. Most of the involved antisense RNAs are regulated and positively correlated with their sense protein-coding genes. We investigated lncRNAs with stimulus specific immunomodulatory activity as potential marker genes: LINC00595, SBF2-AS1 (A.fumigatus) and RP11-588G21.2, RP11-394l13.1 (C.albicans) might be detectable in the early phase of infection and serve as therapeutic targets in the future.},
    doi = {10.1038/srep40598},
    keywords = {Bacterial Infections, genetics, microbiology; Gene Expression Regulation, drug effects; Humans; Monocytes, metabolism; Mycoses, genetics, microbiology; RNA, Antisense, genetics; RNA, Long Noncoding, chemistry, genetics; RNA, Messenger, genetics; RNA, Untranslated, genetics; Vitamin A, metabolism, pharmacology; Vitamin D, metabolism, pharmacology},
    pmid = {28094339},
    }
  • [DOI] T. E. Klassert, J. Bräuer, M. Hölzer, M. Stock, K. Riege, C. Zubiría-Barrera, M. M. Müller, S. Rummler, C. Skerka, M. Marz, and H. Slevogt, “Differential effects of vitamins A and D on the transcriptional landscape of human monocytes during infection,” Sci Rep, vol. 7, p. 40599, 2017.
    [Bibtex]
    @Article{Klassert:17,
    author = {Klassert, Tilman E and Br\"{a}uer, Julia and H\"{o}lzer, Martin and Stock, Magdalena and Riege, Konstantin and Zubir\'{\i}a-Barrera, Cristina and M\"{u}ller, Mario M and Rummler, Silke and Skerka, Christine and Marz, Manja and Slevogt, Hortense},
    title = {Differential Effects of Vitamins {A} and {D} on the Transcriptional Landscape of Human Monocytes during Infection},
    journal = {{Sci Rep}},
    year = {2017},
    volume = {7},
    pages = {40599},
    abstract = {Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.},
    doi = {10.1038/srep40599},
    keywords = {Computational Biology, methods; Gene Expression Profiling; Gene Expression Regulation, drug effects; Humans; Immunologic Factors; Immunomodulation, drug effects; Infection, genetics, immunology, microbiology; Monocytes, drug effects, immunology, metabolism; Transcription, Genetic; Transcriptome; Vitamin A, pharmacology; Vitamin D, pharmacology},
    pmid = {28094291},
    }
  • [DOI] R. Starke, M. Müller, M. Gaspar, M. Marz, K. Küsel, K. U. Totsche, M. von Bergen, and N. Jehmlich, “Candidate Brocadiales dominates C, N and S cycling in anoxic groundwater of a pristine limestone-fracture aquifer,” J Proteomics, vol. 152, p. 153–160, 2017.
    [Bibtex]
    @Article{Starke:17,
    author = {Starke, Robert and Müller, Martina and Gaspar, Michael and Marz, Manja and Küsel, Kirsten and Totsche, Kai Uwe and von Bergen, Martin and Jehmlich, Nico},
    title = {Candidate {B}rocadiales dominates {C}, {N} and {S} cycling in anoxic groundwater of a pristine limestone-fracture aquifer},
    journal = {{J Proteomics}},
    year = {2017},
    volume = {152},
    pages = {153--160},
    abstract = {Groundwater-associated microorganisms are known to play an important role in the biogeochemical C, N and S cycling. Metaproteomics was applied to characterize the diversity and the activity of microbes to identify key species in major biogeochemical processes in the anoxic groundwater of a pristine karstic aquifer located in Hainich, central Germany. Sampling was achieved by pumping 1000L water from two sites of the upper aquifer assemblage and filtration on 0.3μm glass filters. In total, 3808 protein groups were identified. Interestingly, the two wells (H4/2 and H5/2) differed not only in microbial density but also in the prevalence of different C, N and S cycling pathways. The well H5/2 was dominated by the anaerobic ammonia-oxidizing (anammox) candidate Brocadiales (31%) while other orders such as Burkholderiales (2%) or Nitrospirales (3%) were less abundant. Otherwise, the well H4/2 featured only low biomass and remarkably fewer proteins (391 to 3631 at H5/2). Candidate Brocadiales was affiliated to all major carbon fixation strategies, and to the cycling of N and S implying a major role in biogeochemical processes of groundwater aquifers. The findings of our study support functions which can be linked to the ecosystem services provided by the microbial communities present in aquifers. Subsurface environments especially the groundwater ecosystems represent a large habitat for microbial activity. Microbes are responsible for energy and nutrient cycling and are massively involved in the planet's sustainability. Microbial diversity is tremendous and the central question in current microbial ecology is "Who eats what, where and when?". In this study, we characterize a natural aquifer inhabiting microbial community to obtain evidence for the phylogenetic diversity and the metabolic activity by protein abundance and we highlight important biogeochemical cycling processes. The aquifer was dominated by Candidatus Brocadiales while other phylotypes such as Burkholderiales, Caulobacterales and Nitrospirales were less abundant. The candidate comprised all major carbon fixation strategies, ammonification, anammox and denitrification as well as assimilatory sulfate reduction. Our findings have broad implications for the understanding of microbial activities in this aquifer and consequently specific functions can be linked to the ecosystem services provided by the microbial communities present in aquifers.},
    doi = {10.1016/j.jprot.2016.11.003},
    keywords = {Bacteria, isolation & purification, metabolism; Biodiversity; Calcium Carbonate; Carbon, metabolism; Ecosystem; Groundwater, microbiology; Nitrogen, metabolism; Phylogeny; Planctomycetales, metabolism; Sulfur, metabolism; Biogeochemical cycling; Groundwater; Limestone aquifer; Metaproteomics},
    pmid = {27838466},
    }
  • [DOI] G. K. Gerresheim, N. Dünnes, A. Nieder-Röhrmann, L. A. Shalamova, M. Fricke, I. Hofacker, C. Höner Zu Siederdissen, M. Marz, and M. Niepmann, “MicroRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3′ untranslated region: function in replication and influence of RNA secondary structure,” Cell Mol Life Sci, vol. 74, p. 747–760, 2017.
    [Bibtex]
    @Article{Gerresheim:17,
    author = {Gerresheim, Gesche K and D\"{u}nnes, Nadia and Nieder-R\"{o}hrmann, Anika and Shalamova, Lyudmila A and Fricke, Markus and Hofacker, Ivo and H\"{o}ner Zu Siederdissen, Christian and Marz, Manja and Niepmann, Michael},
    title = {micro{RNA}-122 target sites in the hepatitis {C} virus {RNA} {NS5B} coding region and 3' untranslated region: function in replication and influence of {RNA} secondary structure},
    journal = {{Cell Mol Life Sci}},
    year = {2017},
    volume = {74},
    pages = {747--760},
    abstract = {We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle.},
    doi = {10.1007/s00018-016-2377-9},
    issue = {4},
    keywords = {3' Untranslated Regions; 5' Untranslated Regions; Argonaute Proteins, metabolism; Base Sequence; Gene Expression Regulation, Viral; Genome, Viral; HeLa Cells; Hepacivirus, chemistry, genetics, physiology; Hepatitis C, genetics, metabolism, virology; Humans; MicroRNAs, metabolism; Nucleic Acid Conformation; Protein Biosynthesis; RNA, Viral, chemistry, genetics, metabolism; Viral Nonstructural Proteins, genetics; Virus Replication; Accessibility; Ago2; Regulation; Translation; microRNA},
    pmid = {27677491},
    }
  • [DOI] M. Hölzer and M. Marz, “Software dedicated to virus sequence analysis “Bioinformatics goes viral”,” Adv Virus Res, vol. 99, p. 233–257, 2017.
    [Bibtex]
    @Article{Hoelzer:17,
    author = {H\"{o}lzer, Martin and Marz, Manja},
    title = {Software Dedicated to Virus Sequence Analysis "{B}ioinformatics Goes Viral"},
    journal = {{Adv Virus Res}},
    year = {2017},
    volume = {99},
    pages = {233--257},
    abstract = {Computer-assisted technologies of the genomic structure, biological function, and evolution of viruses remain a largely neglected area of research. The attention of bioinformaticians to this challenging field is currently unsatisfying in respect to its medical and biological importance. The power of new genome sequencing technologies, associated with new tools to handle "big data", provides unprecedented opportunities to address fundamental questions in virology. Here, we present an overview of the current technologies, challenges, and advantages of Next-Generation Sequencing (NGS) in relation to the field of virology. We present how viral sequences can be detected de novo out of current short-read NGS data. Furthermore, we discuss the challenges and applications of viral quasispecies and how secondary structures, commonly shaped by RNA viruses, can be computationally predicted. The phylogenetic analysis of viruses, as another ubiquitous field in virology, forms an essential element of describing viral epidemics and challenges current algorithms. Recently, the first specialized virus-bioinformatic organizations have been established. We need to bring together virologists and bioinformaticians and provide a platform for the implementation of interdisciplinary collaborative projects at local and international scales. Above all, there is an urgent need for dedicated software tools to tackle various challenges in virology.},
    doi = {10.1016/bs.aivir.2017.08.004},
    keywords = {Computational Biology, methods; High-Throughput Nucleotide Sequencing; Molecular Epidemiology, methods; Phylogeny; Sequence Analysis, methods; Software; Virology, methods; Viruses, classification, genetics, isolation & purification; Bioinformatics; Software; Virology; Virus sequence analysis},
    pmid = {29029728},
    }
  • [DOI] M. Baumgart, E. Barth, A. Savino, M. Groth, P. Koch, A. Petzold, I. Arisi, M. Platzer, M. Marz, and A. Cellerino, “A miRNA catalogue and ncRNA annotation of the short-living fish Nothobranchius furzeri,” bioRxiv, p. 103697, 2017.
    [Bibtex]
    @Article{Baumgart:17a,
    author = {Mario Baumgart and Emanuel Barth and Aurora Savino and Marco Groth and Philipp Koch and Andreas Petzold and Ivan Arisi and Matthias Platzer and Manja Marz and Alessandro Cellerino},
    title = {A {miRNA} catalogue and {ncRNA} annotation of the short-living fish {N}othobranchius furzeri},
    journal = {{bioRxiv}},
    year = {2017},
    pages = {103697},
    doi = {10.1101/103697},
    publisher = {Cold Spring Harbor Laboratory},
    }

2016

  • [DOI] M. Hölzer, V. Krähling, F. Amman, E. Barth, S. H. Bernhart, V. A. O. Carmelo, M. Collatz, G. Doose, F. Eggenhofer, J. Ewald, J. Fallmann, L. M. Feldhahn, M. Fricke, J. Gebauer, A. J. Gruber, F. Hufsky, H. Indrischek, S. Kanton, J. Linde, N. Mostajo, R. Ochsenreiter, K. Riege, L. Rivarola-Duarte, A. H. Sahyoun, S. J. Saunders, S. E. Seemann, A. Tanzer, B. Vogel, S. Wehner, M. T. Wolfinger, R. Backofen, J. Gorodkin, I. Grosse, I. Hofacker, S. Hoffmann, C. Kaleta, P. F. Stadler, S. Becker, and M. Marz, “Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells,” Sci Rep, vol. 6, p. 34589, 2016.
    [Bibtex]
    @Article{Hoelzer:16,
    author = {H\"{o}lzer, Martin and Kr\"{a}hling, Verena and Amman, Fabian and Barth, Emanuel and Bernhart, Stephan H and Carmelo, Victor A O and Collatz, Maximilian and Doose, Gero and Eggenhofer, Florian and Ewald, Jan and Fallmann, J\"{o}rg and Feldhahn, Lasse M and Fricke, Markus and Gebauer, Juliane and Gruber, Andreas J and Hufsky, Franziska and Indrischek, Henrike and Kanton, Sabina and Linde, J\"{o}rg and Mostajo, Nelly and Ochsenreiter, Roman and Riege, Konstantin and Rivarola-Duarte, Lorena and Sahyoun, Abdullah H and Saunders, Sita J and Seemann, Stefan E and Tanzer, Andrea and Vogel, Bertram and Wehner, Stefanie and Wolfinger, Michael T and Backofen, Rolf and Gorodkin, Jan and Grosse, Ivo and Hofacker, Ivo and Hoffmann, Steve and Kaleta, Christoph and Stadler, Peter F and Becker, Stephan and Marz, Manja},
    title = {Differential transcriptional responses to {E}bola and {M}arburg virus infection in bat and human cells},
    journal = {{Sci Rep}},
    year = {2016},
    volume = {6},
    pages = {34589},
    abstract = {The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.},
    doi = {10.1038/srep34589},
    keywords = {Animals; Cell Line, Tumor; Chiroptera; Ebolavirus, metabolism; Gene Expression Regulation; Hemorrhagic Fever, Ebola, metabolism; Humans; Marburg Virus Disease, metabolism; Marburgvirus, metabolism; Signal Transduction; Transcription, Genetic},
    pmid = {27713552},
    }
  • [DOI] M. Fricke and M. Marz, “Prediction of conserved long-range RNA-RNA interactions in full viral genomes,” Bioinformatics, vol. 32, p. 2928–2935, 2016.
    [Bibtex]
    @Article{Fricke:16,
    author = {Fricke, Markus and Marz, Manja},
    title = {Prediction of conserved long-range {RNA-RNA} interactions in full viral genomes},
    journal = {Bioinformatics},
    year = {2016},
    volume = {32},
    pages = {2928--2935},
    abstract = {Long-range RNA-RNA interactions (LRIs) play an important role in viral replication, however, only a few of these interactions are known and only for a small number of viral species. Up to now, it has been impossible to screen a full viral genome for LRIs experimentally or in silico Most known LRIs are cross-reacting structures (pseudoknots) undetectable by most bioinformatical tools. We present LRIscan, a tool for the LRI prediction in full viral genomes based on a multiple genome alignment. We confirmed 14 out of 16 experimentally known and evolutionary conserved LRIs in genome alignments of HCV, Tombusviruses, Flaviviruses and HIV-1. We provide several promising new interactions, which include compensatory mutations and are highly conserved in all considered viral sequences. Furthermore, we provide reactivity plots highlighting the hot spots of predicted LRIs. Source code and binaries of LRIscan freely available for download at http://www.rna.uni-jena.de/en/supplements/lriscan/, implemented in Ruby/C ++ and supported on Linux and Windows. manja@uni-jena.de Supplementary data are available at Bioinformatics online.},
    doi = {10.1093/bioinformatics/btw323},
    issue = {19},
    keywords = {Computer Simulation; Genome, Viral; RNA, Viral; Sequence Analysis, RNA; Software},
    pmid = {27288498},
    }
  • [DOI] S. Winter, K. Jahn, S. Wehner, L. Kuchenbecker, M. Marz, J. Stoye, and S. Böcker, “Finding approximate gene clusters with Gecko 3,” Nucleic Acids Res, vol. 44, p. 9600–9610, 2016.
    [Bibtex]
    @Article{Winter:16,
    author = {Winter, Sascha and Jahn, Katharina and Wehner, Stefanie and Kuchenbecker, Leon and Marz, Manja and Stoye, Jens and B\"{o}cker, Sebastian},
    title = {Finding approximate gene clusters with {Gecko} 3},
    journal = {{Nucleic Acids Res}},
    year = {2016},
    volume = {44},
    pages = {9600--9610},
    abstract = {Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA-Seq data. The computational analysis is carried out on a laptop computer in <40 min.},
    doi = {10.1093/nar/gkw843},
    issue = {20},
    keywords = {Algorithms; Computational Biology, methods; Datasets as Topic; Genes, Bacterial; Genome, Bacterial; Genomics, methods; Models, Statistical; Multigene Family; Software; Web Browser; Workflow},
    pmid = {27679480},
    }
  • [DOI] M. Hölzer, K. Laroucau, H. H. Creasy, S. Ott, F. Vorimore, P. M. Bavoil, M. Marz, and K. Sachse, "Whole-genome sequence of Chlamydia gallinacea type strain 08-1274/3," Genome Announc, vol. 4, 2016.
    [Bibtex]
    @Article{Hoelzer:16a,
    author = {H\"{o}lzer, Martin and Laroucau, Karine and Creasy, Heather Huot and Ott, Sandra and Vorimore, Fabien and Bavoil, Patrik M and Marz, Manja and Sachse, Konrad},
    title = {Whole-Genome Sequence of {C}hlamydia gallinacea Type Strain 08-1274/3},
    journal = {{Genome Announc}},
    year = {2016},
    volume = {4},
    abstract = {The recently introduced bacterial species Chlamydia gallinacea is known to occur in domestic poultry and other birds. Its potential as an avian pathogen and zoonotic agent is under investigation. The whole-genome sequence of its type strain, 08-1274/3, consists of a 1,059,583-bp chromosome with 914 protein-coding sequences (CDSs) and a plasmid (p1274) comprising 7,619 bp with 9 CDSs. },
    doi = {10.1128/genomeA.00708-16},
    issue = {4},
    pmid = {27445388},
    }
  • [DOI] E. Barth, R. Hübler, A. Baniahmad, and M. Marz, "The evolution of COP9 signalosome in unicellular and multicellular organisms," Genome Biol Evol, vol. 8, p. 1279–1289, 2016.
    [Bibtex]
    @Article{Barth:16,
    author = {Barth, Emanuel and H\"{u}bler, Ron and Baniahmad, Aria and Marz, Manja},
    title = {The Evolution of {COP9} Signalosome in Unicellular and Multicellular Organisms},
    journal = {{Genome Biol Evol}},
    year = {2016},
    volume = {8},
    pages = {1279--1289},
    abstract = {The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions. },
    doi = {10.1093/gbe/evw073},
    issue = {4},
    keywords = {Alternative Splicing; Animals; COP9 Signalosome Complex; Evolution, Molecular; Exons; Humans; Introns; Multiprotein Complexes, genetics; Peptide Hydrolases, genetics; Phylogeny; Protein Subunits, genetics; animal kingdom; bacteria; comparative informatics for plants; fungi; genomic structure; signalosome subunits CSN},
    pmid = {27044515},
    }
  • [DOI] T. Marschall, M. Marz, T. Abeel, L. Dijkstra, B. E. Dutilh, A. Ghaffaari, P. Kersey, W. Kloosterman, V. Makinen, A. Novak, B. Paten, D. Porubsky, E. RIVALS, C. Alkan, J. Baaijens, P. I. W. de Bakker, V. Boeva, R. J. P. Bonnal, F. Chiaromonte, R. Chikhi, F. D. Ciccarelli, R. Cijvat, E. Datema, C. V. M. Duijn, E. E. Eichler, C. Ernst, E. Eskin, E. Garrison, M. El-Kebir, G. W. Klau, J. O. Korbel, E. Lameijer, B. Langmead, M. Martin, P. Medvedev, J. C. Mu, P. Neerincx, K. Ouwens, P. Peterlongo, P. Nadia, S. Rahmann, B. Raphael, K. Reinert, D. de Ridder, J. de Ridder, M. Schlesner, O. Schulz-Trieglaff, A. Sanders, S. Sheikhizadeh, C. Shneider, S. Smit, D. Valenzuela, J. Wang, L. Wessels, Y. Zhang, V. Guryev, F. Vandin, K. Ye, and A. Schoenhuth, "Computational pan-genomics: status, promises and challenges," bioRxiv, p. 43430, 2016.
    [Bibtex]
    @Article{Marschall:16,
    author = {Tobias Marschall and Manja Marz and Thomas Abeel and Louis Dijkstra and Bas E Dutilh and Ali Ghaffaari and Paul Kersey and Wigard Kloosterman and Veli Makinen and Adam Novak and Benedict Paten and David Porubsky and Eric RIVALS and Can Alkan and Jasmijn Baaijens and Paul I. W. de Bakker and Valentina Boeva and Raoul J.P. Bonnal and Francesca Chiaromonte and Rayan Chikhi and Francesca D. Ciccarelli and Robin Cijvat and Erwin Datema and Cornelia M. Van Duijn and Evan E. Eichler and Corinna Ernst and Eleazar Eskin and Erik Garrison and Mohammed El-Kebir and Gunnar W. Klau and Jan O Korbel and Eric-Wubbo Lameijer and Ben Langmead and Marcel Martin and Paul Medvedev and John C. Mu and Pieter Neerincx and Klaasjan Ouwens and Pierre Peterlongo and Pisanti Nadia and Sven Rahmann and Benjamin Raphael and Knut Reinert and Dick de Ridder and Jeroen de Ridder and Matthias Schlesner and Ole Schulz-Trieglaff and Ashley Sanders and Siavash Sheikhizadeh and Carl Shneider and Sandra Smit and Daniel Valenzuela and Jiayin Wang and Lodewyk Wessels and Ying Zhang and Victor Guryev and Fabio Vandin and Kai Ye and Alexander Schoenhuth},
    title = {Computational Pan-Genomics: Status, Promises and Challenges},
    journal = {{bioRxiv}},
    year = {2016},
    pages = {043430},
    doi = {10.1101/043430},
    publisher = {Cold Spring Harbor Laboratory},
    }
  • [DOI] R. Madhugiri, M. Fricke, M. Marz, and J. Ziebuhr, "Coronavirus cis-acting RNA elements," in Coronaviruses, Elsevier, 2016, p. 127–163.
    [Bibtex]
    @InCollection{Madhugiri:16,
    author = {R. Madhugiri and M. Fricke and M. Marz and J. Ziebuhr},
    title = {Coronavirus cis-Acting {RNA} Elements},
    booktitle = {Coronaviruses},
    publisher = {Elsevier},
    year = {2016},
    pages = {127--163},
    doi = {10.1016/bs.aivir.2016.08.007},
    }

2015

  • L. Graf, F. Sendker, A. Dick, E. Barth, M. Marz, O. Daumke, and G. Kochs, "ID: 187: allelic variations in the interferon-induced human MxA protein affect its antiviral activity against influenza A virus," Cytokine, vol. 76, iss. 1, p. 98, 2015.
    [Bibtex]
    @Article{Graf:15,
    author = {Graf, Laura and Sendker, Franziska and Dick, Alexej and Barth, Emanuel and Marz, Manja and Daumke, Oliver and Kochs, Georg},
    title = {{ID}: 187: Allelic variations in the interferon-induced human {MxA} protein affect its antiviral activity against influenza {A} virus},
    journal = {Cytokine},
    year = {2015},
    volume = {76},
    number = {1},
    pages = {98},
    publisher = {Elsevier},
    }
  • [DOI] P. Möbius, M. Hölzer, M. Felder, G. Nordsiek, M. Groth, H. Köhler, K. Reichwald, M. Platzer, and M. Marz, "Comprehensive insights in the Mycobacterium avium subsp. paratuberculosis genome using new WGS data of sheep strain JIII-386 from Germany," Genome Biol Evol, vol. 7, p. 2585–2601, 2015.
    [Bibtex]
    @Article{Moebius:15,
    author = {Möbius, Petra and Hölzer, Martin and Felder, Marius and Nordsiek, Gabriele and Groth, Marco and Köhler, Heike and Reichwald, Kathrin and Platzer, Matthias and Marz, Manja},
    title = {Comprehensive insights in the {M}ycobacterium avium subsp. paratuberculosis genome using new {WGS} data of sheep strain {JIII}-386 from {G}ermany},
    journal = {{Genome Biol Evol}},
    year = {2015},
    volume = {7},
    pages = {2585--2601},
    abstract = {Mycobacterium avium (M. a.) subsp. paratuberculosis (MAP) - the etiologic agent of Johne's disease - affects cattle, sheep and other ruminants worldwide. To decipher phenotypic differences among sheep and cattle strains (belonging to MAP-S [Type-I/III] respectively MAP-C [Type-II]) comparative genome analysis needs data from diverse isolates originating from different geographic regions of the world. The current study presents the so far best assembled genome of a MAP-S-strain: sheep isolate JIII-386 from Germany. One newly sequenced cattle isolate (JII-1961, Germany), four published MAP strains of MAP-C and MAP-S from U.S. and Australia and M. a. subsp. hominissuis (MAH) strain 104 were used for assembly improvement and comparisons. All genomes were annotated by BacProt and results compared with NCBI annotation. Corresponding protein-coding sequences (CDSs) were detected, but also CDSs that were exclusively determined either by NCBI or BacProt. A new Shine-Dalgarno sequence motif (5'AGCTGG3') was extracted. Novel CDSs including PE-PGRS family protein genes and about 80 non-coding RNAs exhibiting high sequence conservation are presented. Previously found genetic differences between MAP-types are partially revised. Four out of ten assumed MAP-S-specific large sequence polymorphism regions (LSP s) are still present in MAP-C strains; new LSP s were identified. Independently of the regional origin of the strains, the number of individual CDSs and single nucleotide variants confirm the strong similarity of MAP-C strains and show higher diversity among MAP-S strains. This study gives ambiguous results regarding the hypothesis that MAP-S is the evolutionary intermediate between MAH and MAP-C, but it clearly shows a higher similarity of MAP to MAH than to M. intracellulare.},
    doi = {10.1093/gbe/evv154},
    issue = {9},
    keywords = {Johne’s disease; MAP-S; SNV/SNP; Shine-Dalgarno sequence; evolution of MAP-types; ncRNA; new LSPSs},
    pmid = {26384038},
    }
  • [DOI] A. H. Sahyoun, M. Hölzer, F. Jühling, C. Höner zu Siederdissen, M. Al-Arab, K. Tout, M. Marz, M. Middendorf, P. F. Stadler, and M. Bernt, "Towards a comprehensive picture of alloacceptor tRNA remolding in metazoan mitochondrial genomes," Nucleic Acids Res, vol. 43, p. 8044–8056, 2015.
    [Bibtex]
    @Article{Sahyoun:15,
    author = {Sahyoun, Abdullah H and H\"{o}lzer, Martin and J\"{u}hling, Frank and H\"{o}ner zu Siederdissen, Christian and Al-Arab, Marwa and Tout, Kifah and Marz, Manja and Middendorf, Martin and Stadler, Peter F and Bernt, Matthias},
    title = {Towards a comprehensive picture of alloacceptor t{RNA} remolding in metazoan mitochondrial genomes},
    journal = {{Nucleic Acids Res}},
    year = {2015},
    volume = {43},
    pages = {8044--8056},
    abstract = {Remolding of tRNAs is a well-documented process in mitochondrial genomes that changes the identity of a tRNA. It involves a duplication of a tRNA gene, a mutation that changes the anticodon and the loss of the ancestral tRNA gene. The net effect is a functional tRNA that is more closely related to tRNAs of a different alloacceptor family than to tRNAs with the same anticodon in related species. Beyond being of interest for understanding mitochondrial tRNA function and evolution, tRNA remolding events can lead to artifacts in the annotation of mitogenomes and thus in studies of mitogenomic evolution. Therefore, it is important to identify and catalog these events. Here we describe novel methods to detect tRNA remolding in large-scale data sets and apply them to survey tRNA remolding throughout animal evolution. We identify several novel remolding events in addition to the ones previously mentioned in the literature. A detailed analysis of these remoldings showed that many of them are derived from ancestral events. },
    doi = {10.1093/nar/gkv746},
    issue = {16},
    keywords = {Animals; Anticodon; Codon; Crustacea, genetics; Evolution, Molecular; Genome, Mitochondrial; Mutation; Porifera, genetics; RNA, Transfer, genetics; RNA, Transfer, Leu, genetics; Sequence Alignment},
    pmid = {26227972},
    }
  • [DOI] M. Fricke, N. Dünnes, M. Zayas, R. Bartenschlager, M. Niepmann, and M. Marz, "Conserved RNA secondary structures and long-range interactions in hepatitis C viruses," RNA, vol. 21, p. 1219–1232, 2015.
    [Bibtex]
    @Article{Fricke:15,
    author = {Fricke, Markus and D\"{u}nnes, Nadia and Zayas, Margarita and Bartenschlager, Ralf and Niepmann, Michael and Marz, Manja},
    title = {Conserved {RNA} secondary structures and long-range interactions in hepatitis {C} viruses},
    journal = {{RNA}},
    year = {2015},
    volume = {21},
    pages = {1219--1232},
    abstract = {Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5' untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3' UTR. We propose an alternative structure in the 5' UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four possible structures of the X-tail at the very 3' end of the HCV genome. We predict several previously unknown long-range interactions, most importantly a possible circularization interaction between distinct elements in the 5' and 3' UTR, reminiscent of the cyclization elements of the related flaviviruses. Based on analogy to these viruses, we propose that the 5'-3' UTR base-pairing in the HCV genome might play an important role in viral RNA replication. These results may have important implications for our understanding of the nature of the cis-acting RNA elements in the HCV genome and their possible role in regulating the mutually exclusive processes of viral RNA translation and replication. },
    doi = {10.1261/rna.049338.114},
    issue = {7},
    keywords = {3' Untranslated Regions; 5' Untranslated Regions; Base Sequence; Hepacivirus, genetics, physiology; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Viral, chemistry; Virus Replication; HCV; RNA long-range interaction prediction; RNA secondary structure prediction; bioinformatics; circularization},
    pmid = {25964384},
    }
  • [DOI] M. Marz, M. Ferracin, and C. Klein, "MicroRNAs as biomarker of Parkinson disease? Small but mighty," Neurology, vol. 84, p. 636–638, 2015.
    [Bibtex]
    @Article{Marz:15,
    author = {Marz, Manja and Ferracin, Manuela and Klein, Christine},
    title = {Micro{RNA}s as biomarker of {P}arkinson disease? {S}mall but mighty},
    journal = {Neurology},
    year = {2015},
    volume = {84},
    pages = {636--638},
    doi = {10.1212/WNL.0000000000001275},
    issue = {7},
    keywords = {Antiparkinson Agents, therapeutic use; Female; Humans; Levodopa, therapeutic use; Male; MicroRNAs, blood; Parkinson Disease, blood},
    pmid = {25596504},
    }
  • [DOI] J. Linde, S. Duggan, M. Weber, F. Horn, P. Sieber, D. Hellwig, K. Riege, M. Marz, R. Martin, R. Guthke, and O. Kurzai, "Defining the transcriptomic landscape of Candida glabrata by RNA-seq," Nucleic Acids Res, vol. 43, p. 1392–1406, 2015.
    [Bibtex]
    @Article{Linde:15,
    author = {Linde, J\"{o}rg and Duggan, Se\'{a}na and Weber, Michael and Horn, Fabian and Sieber, Patricia and Hellwig, Daniela and Riege, Konstantin and Marz, Manja and Martin, Ronny and Guthke, Reinhard and Kurzai, Oliver},
    title = {Defining the transcriptomic landscape of {C}andida glabrata by {RNA}-Seq},
    journal = {{Nucleic Acids Res}},
    year = {2015},
    volume = {43},
    pages = {1392--1406},
    abstract = {Candida glabrata is the second most common pathogenic Candida species and has emerged as a leading cause of nosocomial fungal infections. Its reduced susceptibility to antifungal drugs and its close relationship to Saccharomyces cerevisiae make it an interesting research focus. Although its genome sequence was published in 2004, little is known about its transcriptional dynamics. Here, we provide a detailed RNA-Seq-based analysis of the transcriptomic landscape of C. glabrata in nutrient-rich media, as well as under nitrosative stress and during pH shift. Using RNA-Seq data together with state-of-the-art gene prediction tools, we refined the annotation of the C. glabrata genome and predicted 49 novel protein-coding genes. Of these novel genes, 14 have homologs in S. cerevisiae and six are shared with other Candida species. We experimentally validated four novel protein-coding genes of which two are differentially regulated during pH shift and interaction with human neutrophils, indicating a potential role in host-pathogen interaction. Furthermore, we identified 58 novel non-protein-coding genes, 38 new introns and condition-specific alternative splicing. Finally, our data suggest different patterns of adaptation to pH shift and nitrosative stress in C. glabrata, Candida albicans and S. cerevisiae and thus further underline a distinct evolution of virulence in yeast. },
    doi = {10.1093/nar/gku1357},
    issue = {3},
    keywords = {3' Untranslated Regions; Candida glabrata, genetics; Genes, Fungal; Hydrogen-Ion Concentration; Introns; Nitrosation; Pseudogenes; Real-Time Polymerase Chain Reaction; Saccharomyces cerevisiae, genetics; Sequence Analysis, RNA, methods; Transcriptome},
    pmid = {25586221},
    }

2014

  • [DOI] E. Bauer, H. Salem, M. Marz, H. Vogel, and M. Kaltenpoth, "Transcriptomic immune response of the cotton stainer Dysdercus fasciatus to experimental elimination of vitamin-supplementing intestinal symbionts," PLoS One, vol. 9, p. e114865, 2014.
    [Bibtex]
    @Article{Bauer:14,
    author = {Bauer, Eugen and Salem, Hassan and Marz, Manja and Vogel, Heiko and Kaltenpoth, Martin},
    title = {Transcriptomic immune response of the cotton stainer {D}ysdercus fasciatus to experimental elimination of vitamin-supplementing intestinal symbionts},
    journal = {{PLoS One}},
    year = {2014},
    volume = {9},
    pages = {e114865},
    abstract = {The acquisition and vertical transmission of bacterial symbionts plays an important role in insect evolution and ecology. However, the molecular mechanisms underlying the stable maintenance and control of mutualistic bacteria remain poorly understood. The cotton stainer Dysdercus fasciatus harbours the actinobacterial symbionts Coriobacterium glomerans and Gordonibacter sp. in its midgut. The symbionts supplement limiting B vitamins and thereby significantly contribute to the host's fitness. In this study, we experimentally disrupted the symbionts' vertical transmission route and performed comparative transcriptomic analyses of genes expressed in the gut of aposymbiotic (symbiont-free) and control individuals to study the host immune response in presence and absence of the mutualists. Annotation of assembled cDNA reads identified a considerable number of genes involved in the innate immune system, including different protein isoforms of several immune effector proteins (specifically i-type lysozyme, defensin, hemiptericin, and pyrrhocoricin), suggesting the possibility for a highly differentiated response towards the complex resident microbial community. Gene expression analyses revealed a constitutive expression of transcripts involved in signal transduction of the main insect immune pathways, but differential expression of certain antimicrobial peptide genes. Specifically, qPCRs confirmed the significant down-regulation of c-type lysozyme and up-regulation of hemiptericin in aposymbiotic individuals. The high expression of c-type lysozyme in symbiont-containing bugs may serve to lyse symbiont cells and thereby harvest B-vitamins that are necessary for subsistence on the deficient diet of Malvales seeds. Our findings suggest a sophisticated host response to perturbation of the symbiotic gut microbiota, indicating that the innate immune system not only plays an important role in combating pathogens, but also serves as a communication interface between host and symbionts. },
    doi = {10.1371/journal.pone.0114865},
    issue = {12},
    keywords = {Actinobacteria, physiology; Animals; Antimicrobial Cationic Peptides, metabolism; Biomarkers, metabolism; Dietary Supplements; Gastrointestinal Tract, immunology, metabolism, microbiology; Gene Expression Profiling; Insecta, genetics, immunology, microbiology; Intestines, immunology, metabolism, microbiology; Oligonucleotide Array Sequence Analysis; Phylogeny; RNA, Messenger, genetics; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Symbiosis, physiology; Vitamin B Complex},
    pmid = {25490201},
    }
  • [DOI] R. Madhugiri, M. Fricke, M. Marz, and J. Ziebuhr, "RNA structure analysis of alphacoronavirus terminal genome regions," Virus Res, vol. 194, p. 76–89, 2014.
    [Bibtex]
    @Article{Madhugiri:14,
    author = {Madhugiri, Ramakanth and Fricke, Markus and Marz, Manja and Ziebuhr, John},
    title = {{RNA} structure analysis of alphacoronavirus terminal genome regions},
    journal = {{Virus Res}},
    year = {2014},
    volume = {194},
    pages = {76--89},
    abstract = {Coronavirus genome replication is mediated by a multi-subunit protein complex that is comprised of more than a dozen virally encoded and several cellular proteins. Interactions of the viral replicase complex with cis-acting RNA elements located in the 5' and 3'-terminal genome regions ensure the specific replication of viral RNA. Over the past years, boundaries and structures of cis-acting RNA elements required for coronavirus genome replication have been extensively characterized in betacoronaviruses and, to a lesser extent, other coronavirus genera. Here, we review our current understanding of coronavirus cis-acting elements located in the terminal genome regions and use a combination of bioinformatic and RNA structure probing studies to identify and characterize putative cis-acting RNA elements in alphacoronaviruses. The study suggests significant RNA structure conservation among members of the genus Alphacoronavirus but also across genus boundaries. Overall, the conservation pattern identified for 5' and 3'-terminal RNA structural elements in the genomes of alpha- and betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements. },
    doi = {10.1016/j.virusres.2014.10.001},
    keywords = {Base Sequence; Conserved Sequence; Coronavirus, chemistry, genetics, physiology; Genome, Viral; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Protein Binding; RNA Replicase, metabolism; RNA, Viral, chemistry, genetics; Virus Replication; Coronavirus; RNA structure; RNA virus; Replication; cis-Acting element},
    pmid = {25307890},
    }
  • [DOI] H. Salem, E. Bauer, A. S. Strauss, H. Vogel, M. Marz, and M. Kaltenpoth, "Vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host," Proc Biol Sci, vol. 281, p. 20141838, 2014.
    [Bibtex]
    @Article{Salem:14,
    author = {Salem, Hassan and Bauer, Eugen and Strauss, Anja S and Vogel, Heiko and Marz, Manja and Kaltenpoth, Martin},
    title = {Vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host},
    journal = {{Proc Biol Sci}},
    year = {2014},
    volume = {281},
    pages = {20141838},
    abstract = {Despite the demonstrated functional importance of gut microbes, our understanding of how animals regulate their metabolism in response to nutritionally beneficial symbionts remains limited. Here, we elucidate the functional importance of the African cotton stainer's (Dysdercus fasciatus) association with two actinobacterial gut symbionts and subsequently examine the insect's transcriptional response following symbiont elimination. In line with bioassays demonstrating the symbionts' contribution towards host fitness through the supplementation of B vitamins, comparative transcriptomic analyses of genes involved in import and processing of B vitamins revealed an upregulation of gene expression in aposymbiotic (symbiont-free) compared with symbiotic individuals; an expression pattern that is indicative of B vitamin deficiency in animals. Normal expression levels of these genes, however, can be restored by either artificial supplementation of B vitamins into the insect's diet or reinfection with the actinobacterial symbionts. Furthermore, the functional characterization of the differentially expressed thiamine transporter 2 through heterologous expression in Xenopus laevis oocytes confirms its role in cellular uptake of vitamin B1. These findings demonstrate that despite an extracellular localization, beneficial gut microbes can be integral to the host's metabolic homeostasis, reminiscent of bacteriome-localized intracellular mutualists. },
    doi = {10.1098/rspb.2014.1838},
    issue = {1796},
    keywords = {Actinobacteria, metabolism, physiology; Animal Nutritional Physiological Phenomena; Animals; Biological Transport; Heteroptera, genetics, metabolism, microbiology; Homeostasis; Metabolic Networks and Pathways; Symbiosis; Transcriptome; Vitamin B Complex, biosynthesis; Vitamins, metabolism; Xenopus laevis; host–microbe metabolic integration; mutualism; nutritional symbiosis; symbiont transmission; vitamin supplementation},
    pmid = {25339726},
    }
  • [DOI] J. Qin, M. Fricke, M. Marz, P. F. Stadler, and R. Backofen, "Graph-distance distribution of the Boltzmann ensemble of RNA secondary structures," Algorithms Mol Biol, vol. 9, p. 19, 2014.
    [Bibtex]
    @Article{Qin:14,
    author = {Qin, Jing and Fricke, Markus and Marz, Manja and Stadler, Peter F and Backofen, Rolf},
    title = {Graph-distance distribution of the {B}oltzmann ensemble of {RNA} secondary structures},
    journal = {{Algorithms Mol Biol}},
    year = {2014},
    volume = {9},
    pages = {19},
    abstract = {Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function. Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming. While a naïve implementation would yield recursions with a very high time complexity of O(n (6) D (5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n (4)) for practical applications in which predominantly small distances are of of interest. Further reductions, however, seem to be difficult. Therefore, we introduced sampling approaches that are much easier to implement. They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules. The graph-distance distribution can be computed using a dynamic programming approach. Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data. The additional file and the software of our paper are available from http://www.rna.uni-jena.de/RNAgraphdist.html.},
    doi = {10.1186/1748-7188-9-19},
    keywords = {Boltzmann distribution; Graph-distance; Partition function; Pre-mRNA splicing; smFRET},
    pmid = {25285153},
    }
  • C. Beckstein, S. Böcker, M. Bogdan, H. Bruehlheide, H. M Bücker, J. Denzler, P. Dittrich, I. Grosse, A. Hinneburg, B. König-Ries, F. Löffler, M. Marz, M. Müller-Hannemann, M. Winter, and W. Zimmermann, "Explorative analysis of heterogeneous, unstructured, and uncertain data," in Proceedings of 3rd International Conference on Data Management Technologies and Applications, 2014, p. 251–257.
    [Bibtex]
    @InProceedings{Beckstein:14,
    author = {Beckstein, Clemens and B{\"o}cker, Sebastian and Bogdan, Martin and Bruehlheide, Helge and M B{\"u}cker, H and Denzler, Joachim and Dittrich, Peter and Grosse, Ivo and Hinneburg, Alexander and K{\"o}nig-Ries, Birgitta and Löffler, Felicitas and Marz, Manja and Müller-Hannemann, M. and Winter, M. and Zimmermann, W.},
    title = {Explorative Analysis of Heterogeneous, Unstructured, and Uncertain Data},
    booktitle = {{Proceedings of 3rd International Conference on Data Management Technologies and Applications}},
    year = {2014},
    pages = {251--257},
    }
  • [DOI] S. Wehner, K. Damm, R. K. Hartmann, and M. Marz, "Dissemination of 6S RNA among bacteria," RNA Biol, vol. 11, p. 1467–1478, 2014.
    [Bibtex]
    @Article{Wehner:14,
    author = {Wehner, Stefanie and Damm, Katrin and Hartmann, Roland K and Marz, Manja},
    title = {Dissemination of {6S} {RNA} among bacteria},
    journal = {{RNA Biol}},
    year = {2014},
    volume = {11},
    pages = {1467--1478},
    abstract = {6S RNA is a highly abundant small non-coding RNA widely spread among diverse bacterial groups. By competing with DNA promoters for binding to RNA polymerase (RNAP), the RNA regulates transcription on a global scale. RNAP produces small product RNAs derived from 6S RNA as template, which rearranges the 6S RNA structure leading to dissociation of 6S RNA:RNAP complexes. Although 6S RNA has been experimentally analysed in detail for some species, such as Escherichia coli and Bacillus subtilis, and was computationally predicted in many diverse bacteria, a complete and up-to-date overview of the distribution among all bacteria is missing. In this study we searched with new methods for 6S RNA genes in all currently available bacterial genomes. We ended up with a set of 1,750 6S RNA genes, of which 1,367 are novel and bona fide, distributed among 1,610 bacteria, and had a few tentative candidates among the remaining 510 assembled bacterial genomes accessible. We were able to confirm two tentative candidates by Northern blot analysis. We extended 6S RNA genes of the Flavobacteriia significantly in length compared to the present Rfam entry. We describe multiple homologs of 6S RNAs (including split 6S RNA genes) and performed a detailed synteny analysis. },
    doi = {10.4161/rna.29894},
    issue = {11},
    keywords = {Bacteria, classification, genetics; Blotting, Northern; DNA-Directed RNA Polymerases, metabolism; Gene Expression Regulation, Bacterial; Genome, Bacterial, genetics; Nucleic Acid Conformation; Phylogeny; Promoter Regions, Genetic, genetics; Protein Binding; RNA, Bacterial, chemistry, classification, genetics, metabolism; RNA, Small Untranslated, chemistry, classification, genetics; RNA, Untranslated, classification, genetics, metabolism; Species Specificity; Synteny; 6S RNA; RNA polymerase; non-coding RNA; regulation of transcription; secondary structure},
    pmid = {25483037},
    }
  • [DOI] M. Marz, N. Beerenwinkel, C. Drosten, M. Fricke, D. Frishman, I. L. Hofacker, D. Hoffmann, M. Middendorf, T. Rattei, P. F. Stadler, and A. Töfer, "Challenges in RNA virus bioinformatics," Bioinformatics, vol. 30, p. 1793–1799, 2014.
    [Bibtex]
    @Article{Marz:14,
    author = {Marz, Manja and Beerenwinkel, Niko and Drosten, Christian and Fricke, Markus and Frishman, Dmitrij and Hofacker, Ivo L and Hoffmann, Dieter and Middendorf, Martin and Rattei, Thomas and Stadler, Peter F and T\"{o}fer, Armin},
    title = {Challenges in {RNA} virus bioinformatics},
    journal = {Bioinformatics},
    year = {2014},
    volume = {30},
    pages = {1793--1799},
    abstract = {Computer-assisted studies of structure, function and evolution of viruses remains a neglected area of research. The attention of bioinformaticians to this interesting and challenging field is far from commensurate with its medical and biotechnological importance. It is telling that out of >200 talks held at ISMB 2013, the largest international bioinformatics conference, only one presentation explicitly dealt with viruses. In contrast to many broad, established and well-organized bioinformatics communities (e.g. structural genomics, ontologies, next-generation sequencing, expression analysis), research groups focusing on viruses can probably be counted on the fingers of two hands. The purpose of this review is to increase awareness among bioinformatics researchers about the pressing needs and unsolved problems of computational virology. We focus primarily on RNA viruses that pose problems to many standard bioinformatics analyses owing to their compact genome organization, fast mutation rate and low evolutionary conservation. We provide an overview of tools and algorithms for handling viral sequencing data, detecting functionally important RNA structures, classifying viral proteins into families and investigating the origin and evolution of viruses.},
    doi = {10.1093/bioinformatics/btu105},
    issue = {13},
    keywords = {Animals; Computational Biology, methods; Evolution, Molecular; High-Throughput Nucleotide Sequencing; Humans; Phylogeny; RNA Viruses, genetics; RNA, Viral, chemistry, genetics},
    pmid = {24590443},
    }
  • [DOI] M. Lechner, A. I. Nickel, S. Wehner, K. Riege, N. Wieseke, B. M. Beckmann, R. K. Hartmann, and M. Marz, "Genomewide comparison and novel ncRNAs of Aquificales," BMC Genomics, vol. 15, p. 522, 2014.
    [Bibtex]
    @Article{Lechner:14,
    author = {Lechner, Marcus and Nickel, Astrid I and Wehner, Stefanie and Riege, Konstantin and Wieseke, Nicolas and Beckmann, Benedikt M and Hartmann, Roland K and Marz, Manja},
    title = {Genomewide comparison and novel nc{RNA}s of {A}quificales},
    journal = {{BMC Genomics}},
    year = {2014},
    volume = {15},
    pages = {522},
    abstract = {The Aquificales are a diverse group of thermophilic bacteria that thrive in terrestrial and marine hydrothermal environments. They can be divided into the families Aquificaceae, Desulfurobacteriaceae and Hydrogenothermaceae. Although eleven fully sequenced and assembled genomes are available, only little is known about this taxonomic order in terms of RNA metabolism. In this work, we compare the available genomes, extend their protein annotation, identify regulatory sequences, annotate non-coding RNAs (ncRNAs) of known function, predict novel ncRNA candidates, show idiosyncrasies of the genetic decoding machinery, present two different types of transfer-messenger RNAs and variations of the CRISPR systems. Furthermore, we performed a phylogenetic analysis of the Aquificales based on entire genome sequences, and extended this by a classification among all bacteria using 16S rRNA sequences and a set of orthologous proteins.Combining several in silico features (e.g. conserved and stable secondary structures, GC-content, comparison based on multiple genome alignments) with an in vivo dRNA-seq transcriptome analysis of Aquifex aeolicus, we predict roughly 100 novel ncRNA candidates in this bacterium. We have here re-analyzed the Aquificales, a group of bacteria thriving in extreme environments, sharing the feature of a small, compact genome with a reduced number of protein and ncRNA genes. We present several classical ncRNAs and riboswitch candidates. By combining in silico analysis with dRNA-seq data of A. aeolicus we predict nearly 100 novel ncRNA candidates.},
    doi = {10.1186/1471-2164-15-522},
    keywords = {Base Sequence; Clustered Regularly Interspaced Short Palindromic Repeats, genetics; Databases, Genetic; Digoxigenin, chemistry; Genome, Bacterial; Gram-Positive Bacteria, classification, genetics; Nucleic Acid Conformation; Oligonucleotides, chemistry, metabolism; Phylogeny; RNA, Bacterial, chemistry, metabolism; RNA, Ribosomal, 16S, chemistry, genetics; RNA, Transfer, metabolism; RNA, Untranslated, chemistry, genetics, metabolism; Ribonuclease P, metabolism; Sequence Analysis, RNA},
    pmid = {24965762},
    }
  • [DOI] S. Wehner, G. K. Mannala, X. Qing, R. Madhugiri, T. Chakraborty, M. A. Mraheil, T. Hain, and M. Marz, "Detection of very long antisense transcripts by whole transcriptome RNA-Seq analysis of Listeria monocytogenes by semiconductor sequencing technology," PLoS One, vol. 9, p. e108639, 2014.
    [Bibtex]
    @Article{Wehner:14a,
    author = {Wehner, Stefanie and Mannala, Gopala K and Qing, Xiaoxing and Madhugiri, Ramakanth and Chakraborty, Trinad and Mraheil, Mobarak A and Hain, Torsten and Marz, Manja},
    title = {Detection of very long antisense transcripts by whole transcriptome {RNA-Seq} analysis of {L}isteria monocytogenes by semiconductor sequencing technology},
    journal = {{PLoS One}},
    year = {2014},
    volume = {9},
    pages = {e108639},
    abstract = {The Gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a severe food-borne infection characterised by abortion, septicaemia, or meningoencephalitis. L. monocytogenes causes outbreaks of febrile gastroenteritis and accounts for community-acquired bacterial meningitis in humans. Listeriosis has one of the highest mortality rates (up to 30%) of all food-borne infections. This human pathogenic bacterium is an important model organism for biomedical research to investigate cell-mediated immunity. L. monocytogenes is also one of the best characterised bacterial systems for the molecular analysis of intracellular parasitism. Recently several transcriptomic studies have also made the ubiquitous distributed bacterium as a model to understand mechanisms of gene regulation from the environment to the infected host on the level of mRNA and non-coding RNAs (ncRNAs). We have used semiconductor sequencing technology for RNA-seq to investigate the repertoire of listerial ncRNAs under extra- and intracellular growth conditions. Furthermore, we applied a new bioinformatic analysis pipeline for detection, comparative genomics and structural conservation to identify ncRNAs. With this work, in total, 741 ncRNA locations of potential ncRNA candidates are now known for L. monocytogenes, of which 611 ncRNA candidates were identified by RNA-seq. 441 transcribed ncRNAs have never been described before. Among these, we identified novel long non-coding antisense RNAs with a length of up to 5,400 nt e.g. opposite to genes coding for internalins, methylases or a high-affinity potassium uptake system, namely the kdpABC operon, which were confirmed by qRT-PCR analysis. RNA-seq, comparative genomics and structural conservation of L. monocytogenes ncRNAs illustrate that this human pathogen uses a large number and repertoire of ncRNA including novel long antisense RNAs, which could be important for intracellular survival within the infected eukaryotic host. },
    doi = {10.1371/journal.pone.0108639},
    issue = {10},
    keywords = {Animals; Bacterial Proteins, genetics, metabolism; Cell Line; DNA (Cytosine-5-)-Methyltransferases, metabolism; Gene Expression Regulation, Bacterial; Genetic Association Studies; Humans; Listeria monocytogenes, genetics; Mice; Operon, genetics; RNA, Antisense, genetics; RNA, Untranslated, genetics; Reproducibility of Results; Semiconductors; Sequence Analysis, RNA, methods; Transcription, Genetic; Transcriptome, genetics},
    pmid = {25286309},
    }
  • [DOI] V. U. Schwartze, S. Winter, E. Shelest, M. Marcet-Houben, F. Horn, S. Wehner, J. Linde, V. Valiante, M. Sammeth, K. Riege, M. Nowrousian, K. Kaerger, I. D. Jacobsen, M. Marz, A. A. Brakhage, T. Gabaldón, S. Böcker, and K. Voigt, "Gene expansion shapes genome architecture in the human pathogen Lichtheimia corymbifera: an evolutionary genomics analysis in the ancient terrestrial mucorales (Mucoromycotina)," PLos Genet, vol. 10, p. e1004496, 2014.
    [Bibtex]
    @Article{Schwartze:14,
    author = {Schwartze, Volker U and Winter, Sascha and Shelest, Ekaterina and Marcet-Houben, Marina and Horn, Fabian and Wehner, Stefanie and Linde, J\"{o}rg and Valiante, Vito and Sammeth, Michael and Riege, Konstantin and Nowrousian, Minou and Kaerger, Kerstin and Jacobsen, Ilse D and Marz, Manja and Brakhage, Axel A and Gabald\'{o}n, Toni and B\"{o}cker, Sebastian and Voigt, Kerstin},
    title = {Gene expansion shapes genome architecture in the human pathogen {L}ichtheimia corymbifera: an evolutionary genomics analysis in the ancient terrestrial mucorales ({M}ucoromycotina)},
    journal = {{PLos Genet}},
    year = {2014},
    volume = {10},
    pages = {e1004496},
    abstract = {Lichtheimia species are the second most important cause of mucormycosis in Europe. To provide broader insights into the molecular basis of the pathogenicity-associated traits of the basal Mucorales, we report the full genome sequence of L. corymbifera and compared it to the genome of Rhizopus oryzae, the most common cause of mucormycosis worldwide. The genome assembly encompasses 33.6 MB and 12,379 protein-coding genes. This study reveals four major differences of the L. corymbifera genome to R. oryzae: (i) the presence of an highly elevated number of gene duplications which are unlike R. oryzae not due to whole genome duplication (WGD), (ii) despite the relatively high incidence of introns, alternative splicing (AS) is not frequently observed for the generation of paralogs and in response to stress, (iii) the content of repetitive elements is strikingly low (<5%), (iv) L. corymbifera is typically haploid. Novel virulence factors were identified which may be involved in the regulation of the adaptation to iron-limitation, e.g. LCor01340.1 encoding a putative siderophore transporter and LCor00410.1 involved in the siderophore metabolism. Genes encoding the transcription factors LCor08192.1 and LCor01236.1, which are similar to GATA type regulators and to calcineurin regulated CRZ1, respectively, indicating an involvement of the calcineurin pathway in the adaption to iron limitation. Genes encoding MADS-box transcription factors are elevated up to 11 copies compared to the 1-4 copies usually found in other fungi. More findings are: (i) lower content of tRNAs, but unique codons in L. corymbifera, (ii) Over 25% of the proteins are apparently specific for L. corymbifera. (iii) L. corymbifera contains only 2/3 of the proteases (known to be essential virulence factors) in comparison to R. oryzae. On the other hand, the number of secreted proteases, however, is roughly twice as high as in R. oryzae.},
    doi = {10.1371/journal.pgen.1004496},
    issue = {8},
    keywords = {Alternative Splicing, genetics; Evolution, Molecular; Gene Duplication; Genome, Fungal; Genomics; Humans; Mucorales, genetics, pathogenicity; Mucormycosis, genetics, microbiology; Virulence Factors, genetics, isolation & purification},
    pmid = {25121733},
    }
  • [DOI] S. Wehner, A. K. Dörrich, P. Ciba, A. Wilde, and M. Marz, "pRNA: NoRC-associated RNA of rRNA operons," RNA Biol, vol. 11, p. 3–9, 2014.
    [Bibtex]
    @Article{Wehner:14b,
    author = {Wehner, Stefanie and D\"{o}rrich, Anja K and Ciba, Philipp and Wilde, Annegret and Marz, Manja},
    title = {{pRNA}: {NoRC}-associated {RNA} of r{RNA} operons},
    journal = {{RNA Biol}},
    year = {2014},
    volume = {11},
    pages = {3--9},
    abstract = {Promoter-associated RNAs (pRNAs) are a family of ~90-100 nt-long divergent RNAs overlapping the promoter of the rRNA (rDNA) operon. pRNA transcripts interact with TIP5, a component of the chromatin remodeling complex NoRC, which recruits enzymes for heterochromatin formation and mediates silencing of rRNA genes. Here we present a comprehensive analysis of pRNA homologs, including different versions per species, as result of in silico studies in available metazoan genome assemblies. Comparative sequence analysis and secondary structure prediction ended up in two possible secondary structures, which let us assume a possible dual function of pRNAs for regulation of rRNA operons. Furthermore, we validated parts of our computational predictions experimentally by RT-PCR and sequencing. A representative seed alignment of the pRNA family, annotated with possible secondary structures was released to the Rfam database. },
    doi = {10.4161/rna.27448},
    issue = {1},
    keywords = {Animals; Base Sequence; DNA, Ribosomal, chemistry; Genes, rRNA; Genome; Heterochromatin, metabolism; Humans; Inverted Repeat Sequences; Molecular Structure; Phylogeny; Reproducibility of Results; Sequence Homology, Nucleic Acid; rRNA Operon, genetics; gene silencing; non-coding RNA; promoter-associated RNA; ribosomal RNA},
    pmid = {24440945},
    }
  • [DOI] K. Sachse, K. Laroucau, K. Riege, S. Wehner, M. Dilcher, H. H. Creasy, M. Weidmann, G. Myers, F. Vorimore, N. Vicari, S. Magnino, E. Liebler-Tenorio, A. Ruettger, P. M. Bavoil, F. T. Hufert, R. Rosselló-Móra, and M. Marz, "Evidence for the existence of two new members of the family Chlamydiaceae and proposal of Chlamydia avium sp. nov. and Chlamydia gallinacea sp. nov.," Syst Appl Microbiol, vol. 37, p. 79–88, 2014.
    [Bibtex]
    @Article{Sachse:14,
    author = {Sachse, Konrad and Laroucau, Karine and Riege, Konstantin and Wehner, Stefanie and Dilcher, Meik and Creasy, Heather Huot and Weidmann, Manfred and Myers, Garry and Vorimore, Fabien and Vicari, Nadia and Magnino, Simone and Liebler-Tenorio, Elisabeth and Ruettger, Anke and Bavoil, Patrik M and Hufert, Frank T and Rossell\'{o}-M\'{o}ra, Ramon and Marz, Manja},
    title = {Evidence for the existence of two new members of the family {C}hlamydiaceae and proposal of {C}hlamydia avium sp. nov. and {C}hlamydia gallinacea sp. nov.},
    journal = {{Syst Appl Microbiol}},
    year = {2014},
    volume = {37},
    pages = {79--88},
    abstract = {The family Chlamydiaceae with the recombined single genus Chlamydia currently comprises nine species, all of which are obligate intracellular organisms distinguished by a unique biphasic developmental cycle. Anecdotal evidence from epidemiological surveys in flocks of poultry, pigeons and psittacine birds have indicated the presence of non-classified chlamydial strains, some of which may act as pathogens. In the present study, phylogenetic analysis of ribosomal RNA and ompA genes, as well as multi-locus sequence analysis of 11 field isolates were conducted. All independent analyses assigned the strains into two different clades of monophyletic origin corresponding to pigeon and psittacine strains or poultry isolates, respectively. Comparative genome analysis involving the type strains of currently accepted Chlamydiaceae species and the designated type strains representing the two new clades confirmed that the latter could be classified into two different species as their average nucleotide identity (ANI) values were always below 94%, both with the closest relative species and between themselves. In view of the evidence obtained from the analyses, we propose the addition of two new species to the current classification: Chlamydia avium sp. nov. comprising strains from pigeons and psittacine birds (type strain 10DC88(T); DSMZ: DSM27005(T), CSUR: P3508(T)) and Chlamydia gallinacea sp. nov. comprising strains from poultry (type strain 08-1274/3(T); DSMZ: DSM27451(T), CSUR: P3509(T)). },
    doi = {10.1016/j.syapm.2013.12.004},
    issue = {2},
    keywords = {Animals; Bacterial Outer Membrane Proteins, genetics; Birds, microbiology; Cells, Cultured; Cercopithecus aethiops; Chlamydia, classification, genetics, isolation & purification; Cluster Analysis; DNA, Bacterial, chemistry, genetics; DNA, Ribosomal, chemistry, genetics; Microscopy, Electron, Transmission; Molecular Sequence Data; Phylogeny; Poultry, microbiology; RNA, Ribosomal, 16S, genetics; Sequence Analysis, DNA; 16S rRNA gene sequence; Chlamydia avium; Chlamydia gallinacea; Chlamydiaceae; Comparative genome analysis; Multi-locus sequence analysis},
    pmid = {24461712},
    }
  • [DOI] M. Marz, S. Wehner, and P. F. Stadler, "Homology search for small structured non-coding RNAs," in Handbook of RNA Biochemistry, Wiley-VCH Verlag GmbH & Co. KGaA, 2014, p. 619–632.
    [Bibtex]
    @InCollection{Marz:14a,
    author = {Manja Marz and Stefanie Wehner and Peter F. Stadler},
    title = {Homology Search for Small Structured Non-coding {RNAs}},
    booktitle = {{Handbook of {RNA} Biochemistry}},
    publisher = {Wiley-VCH Verlag GmbH \& Co. KGaA},
    year = {2014},
    pages = {619--632},
    doi = {10.1002/9783527647064.ch29},
    }

2013

  • [DOI] Y. Huang, Y. Li, D. W. Burt, H. Chen, Y. Zhang, W. Qian, H. Kim, S. Gan, Y. Zhao, J. Li, K. Yi, H. Feng, P. Zhu, B. Li, Q. Liu, S. Fairley, K. E. Magor, Z. Du, X. Hu, L. Goodman, H. Tafer, A. Vignal, T. Lee, K. Kim, Z. Sheng, Y. An, S. Searle, J. Herrero, M. A. M. Groenen, R. P. M. A. Crooijmans, T. Faraut, Q. Cai, R. G. Webster, J. R. Aldridge, W. C. Warren, S. Bartschat, S. Kehr, M. Marz, P. F. Stadler, J. Smith, R. H. S. Kraus, Y. Zhao, L. Ren, J. Fei, M. Morisson, P. Kaiser, D. K. Griffin, M. Rao, F. Pitel, J. Wang, and N. Li, "The duck genome and transcriptome provide insight into an avian influenza virus reservoir species," Nat Genet, vol. 45, p. 776–783, 2013.
    [Bibtex]
    @Article{Huang:13,
    author = {Huang, Yinhua and Li, Yingrui and Burt, David W and Chen, Hualan and Zhang, Yong and Qian, Wubin and Kim, Heebal and Gan, Shangquan and Zhao, Yiqiang and Li, Jianwen and Yi, Kang and Feng, Huapeng and Zhu, Pengyang and Li, Bo and Liu, Qiuyue and Fairley, Suan and Magor, Katharine E and Du, Zhenlin and Hu, Xiaoxiang and Goodman, Laurie and Tafer, Hakim and Vignal, Alain and Lee, Taeheon and Kim, Kyu-Won and Sheng, Zheya and An, Yang and Searle, Steve and Herrero, Javier and Groenen, Martien A M and Crooijmans, Richard P M A and Faraut, Thomas and Cai, Qingle and Webster, Robert G and Aldridge, Jerry R and Warren, Wesley C and Bartschat, Sebastian and Kehr, Stephanie and Marz, Manja and Stadler, Peter F and Smith, Jacqueline and Kraus, Robert H S and Zhao, Yaofeng and Ren, Liming and Fei, Jing and Morisson, Mireille and Kaiser, Pete and Griffin, Darren K and Rao, Man and Pitel, Frederique and Wang, Jun and Li, Ning},
    title = {The duck genome and transcriptome provide insight into an avian influenza virus reservoir species},
    journal = {{Nat Genet}},
    year = {2013},
    volume = {45},
    pages = {776--783},
    abstract = {The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses. },
    doi = {10.1038/ng.2657},
    issue = {7},
    keywords = {Animals; Base Sequence; Chickens, genetics; Disease Reservoirs; Disease Vectors; Ducks, genetics, immunology, virology; Female; Geese, genetics; Genome, physiology; Host-Pathogen Interactions, genetics, immunology; Immunity, genetics; Influenza in Birds, genetics, immunology; Molecular Sequence Data; Phylogeny; Species Specificity; Transcriptome, genetics},
    nlm = {EMS58073},
    pmid = {23749191},
    }
  • [DOI] X. Qi, Y. Li, S. Honda, S. Hoffmann, M. Marz, A. Mosig, J. D. Podlevsky, P. F. Stadler, E. U. Selker, and J. J-L. Chen, "The common ancestral core of vertebrate and fungal telomerase RNAs," Nucleic Acids Res, vol. 41, p. 450–462, 2013.
    [Bibtex]
    @Article{Qi:13,
    author = {Qi, Xiaodong and Li, Yang and Honda, Shinji and Hoffmann, Steve and Marz, Manja and Mosig, Axel and Podlevsky, Joshua D and Stadler, Peter F and Selker, Eric U and Chen, Julian J-L},
    title = {The common ancestral core of vertebrate and fungal telomerase {RNA}s},
    journal = {{Nucleic Acids Res}},
    year = {2013},
    volume = {41},
    pages = {450--462},
    abstract = {Telomerase is a ribonucleoprotein with an intrinsic telomerase RNA (TER) component. Within yeasts, TER is remarkably large and presents little similarity in secondary structure to vertebrate or ciliate TERs. To better understand the evolution of fungal telomerase, we identified 74 TERs from Pezizomycotina and Taphrinomycotina subphyla, sister clades to budding yeasts. We initially identified TER from Neurospora crassa using a novel deep-sequencing-based approach, and homologous TER sequences from available fungal genome databases by computational searches. Remarkably, TERs from these non-yeast fungi have many attributes in common with vertebrate TERs. Comparative phylogenetic analysis of highly conserved regions within Pezizomycotina TERs revealed two core domains nearly identical in secondary structure to the pseudoknot and CR4/5 within vertebrate TERs. We then analyzed N. crassa and Schizosaccharomyces pombe telomerase reconstituted in vitro, and showed that the two RNA core domains in both systems can reconstitute activity in trans as two separate RNA fragments. Furthermore, the primer-extension pulse-chase analysis affirmed that the reconstituted N. crassa telomerase synthesizes TTAGGG repeats with high processivity, a common attribute of vertebrate telomerase. Overall, this study reveals the common ancestral cores of vertebrate and fungal TERs, and provides insights into the molecular evolution of fungal TER structure and function.},
    doi = {10.1093/nar/gks980},
    issue = {1},
    keywords = {Animals; Ascomycota, classification, genetics; Base Sequence; Evolution, Molecular; Molecular Sequence Data; Neurospora crassa, enzymology, genetics; Nucleic Acid Conformation; RNA, chemistry; RNA, Fungal, chemistry; Schizosaccharomyces, enzymology, genetics; Telomerase, chemistry, metabolism; Vertebrates, genetics},
    pmid = {23093598},
    }
  • [DOI] Y. Li, J. D. Podlevsky, M. Marz, X. Qi, S. Hoffmann, P. F. Stadler, and J. J-L. Chen, "Identification of purple sea urchin telomerase RNA using a next-generation sequencing based approach," RNA, vol. 19, p. 852–860, 2013.
    [Bibtex]
    @Article{Li:13,
    author = {Li, Yang and Podlevsky, Joshua D and Marz, Manja and Qi, Xiaodong and Hoffmann, Steve and Stadler, Peter F and Chen, Julian J-L},
    title = {Identification of purple sea urchin telomerase {RNA} using a next-generation sequencing based approach},
    journal = {{RNA}},
    year = {2013},
    volume = {19},
    pages = {852--860},
    abstract = {Telomerase is a ribonucleoprotein (RNP) enzyme essential for telomere maintenance and chromosome stability. While the catalytic telomerase reverse transcriptase (TERT) protein is well conserved across eukaryotes, telomerase RNA (TR) is extensively divergent in size, sequence, and structure. This diversity prohibits TR identification from many important organisms. Here we report a novel approach for TR discovery that combines in vitro TR enrichment from total RNA, next-generation sequencing, and a computational screening pipeline. With this approach, we have successfully identified TR from Strongylocentrotus purpuratus (purple sea urchin) from the phylum Echinodermata. Reconstitution of activity in vitro confirmed that this RNA is an integral component of sea urchin telomerase. Comparative phylogenetic analysis against vertebrate TR sequences revealed that the purple sea urchin TR contains vertebrate-like template-pseudoknot and H/ACA domains. While lacking a vertebrate-like CR4/5 domain, sea urchin TR has a unique central domain critical for telomerase activity. This is the first TR identified from the previously unexplored invertebrate clade and provides the first glimpse of TR evolution in the deuterostome lineage. Moreover, our TR discovery approach is a significant step toward the comprehensive understanding of telomerase RNP evolution.},
    doi = {10.1261/rna.039131.113},
    issue = {6},
    keywords = {Animals; Base Sequence; Cloning, Molecular; Computational Biology, methods; DNA, Complementary, genetics, metabolism; Enzyme Activation; Enzyme Assays; Evolution, Molecular; Gene Library; Genetic Loci; Gonads, cytology; Molecular Sequence Data; Nucleic Acid Conformation; Phylogeny; Protein Structure, Tertiary; RNA, classification, genetics, metabolism; RNA, Messenger, genetics, metabolism; Sequence Alignment; Strongylocentrotus purpuratus, classification, enzymology, genetics; Telomerase, classification, genetics, metabolism; next-generation sequencing; ribonucleoprotein; telomerase RNA; telomere},
    pmid = {23584428},
    }
  • [DOI] M. Lechner, M. Marz, C. Ihling, A. Sinz, P. F. Stadler, and V. Krauss, "The correlation of genome size and DNA methylation rate in metazoans," Theory Biosci, vol. 132, p. 47–60, 2013.
    [Bibtex]
    @Article{Lechner:13,
    author = {Lechner, Marcus and Marz, Manja and Ihling, Christian and Sinz, Andrea and Stadler, Peter F and Krauss, Veiko},
    title = {The correlation of genome size and {DNA} methylation rate in metazoans},
    journal = {{Theory Biosci}},
    year = {2013},
    volume = {132},
    pages = {47--60},
    abstract = {Total DNA methylation rates are well known to vary widely between different metazoans. The phylogenetic distribution of this variation, however, has not been investigated systematically. We combine here publicly available data on methylcytosine content with the analysis of nucleotide compositions of genomes and transcriptomes of 78 metazoan species to trace the evolution of abundance and distribution of DNA methylation. The depletion of CpG and the associated enrichment of TpG and CpA dinucleotides are used to infer the intensity and localization of germline CpG methylation and to estimate its evolutionary dynamics. We observe a positive correlation of the relative methylation of CpG motifs with genome size. We tested this trend successfully by measuring total DNA methylation with LC/MS in orthopteran insects with very different genome sizes: house crickets, migratory locusts and meadow grasshoppers. We hypothesize that the observed correlation between methylation rate and genome size is due to a dependence of both variables from long-term effective population size and is driven by the accumulation of repetitive sequences that are typically methylated during periods of small population sizes. This process may result in generally methylated, large genomes such as those of jawed vertebrates. In this case, the emergence of a novel demethylation pathway and of novel reader proteins for methylcytosine may have enabled the usage of cytosine methylation for promoter-based gene regulation. On the other hand, persistently large populations may lead to a compression of the genome and to the loss of the DNA methylation machinery, as observed, e.g., in nematodes.},
    doi = {10.1007/s12064-012-0167-y},
    issue = {1},
    keywords = {5-Methylcytosine, metabolism; Animals; CpG Islands; DNA, chemistry, genetics; DNA Methylation; Genome Size; Orthoptera, genetics, metabolism; Phylogeny; RNA, Ribosomal, chemistry, genetics; Sequence Alignment},
    pmid = {23132463},
    }
  • [DOI] J. Vierna, S. Wehner, C. Höner zu Siederdissen, A. Martínez-Lage, and M. Marz, "Systematic analysis and evolution of 5S ribosomal DNA in metazoans," Heredity, vol. 111, p. 410–421, 2013.
    [Bibtex]
    @Article{Vierna:13,
    author = {Vierna, J and Wehner, S and H\"{o}ner zu Siederdissen, C and Mart\'{\i}nez-Lage, A and Marz, M},
    title = {Systematic analysis and evolution of {5S} ribosomal {DNA} in metazoans},
    journal = {Heredity},
    year = {2013},
    volume = {111},
    pages = {410--421},
    abstract = {Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12,766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades.},
    doi = {10.1038/hdy.2013.63},
    issue = {5},
    keywords = {Animals; Base Sequence; Consensus Sequence; Evolution, Molecular; Gene Dosage; Genetic Linkage; Inverted Repeat Sequences; Molecular Sequence Data; Promoter Regions, Genetic; RNA, Ribosomal, 5S, genetics; RNA, Small Nuclear, genetics; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid},
    pmid = {23838690},
    }
  • R. Backofen, M. Fricke, M. Marz, J. Qin, and P. F. Stadler, "Distribution of graph-distances in Boltzmann ensembles of RNA secondary structures," in International Workshop on Algorithms in Bioinformatics, 2013, p. 112–125.
    [Bibtex]
    @InProceedings{Backofen:13,
    author = {Backofen, Rolf and Fricke, Markus and Marz, Manja and Qin, Jing and Stadler, Peter F},
    title = {Distribution of graph-distances in {B}oltzmann ensembles of {RNA} secondary structures},
    booktitle = {{International Workshop on Algorithms in Bioinformatics}},
    year = {2013},
    pages = {112--125},
    }
  • [DOI] N. Wieseke, M. Lechner, M. Ludwig, and M. Marz, "POMAGO: multiple genome-wide alignment tool for bacteria," in Proceedings of the 9th International Symposium on Bioinformatics Research and Applications (ISBRA 2013), Charlotte, NC, USA, May 20-22, 2013., 2013, p. pp 249-260.
    [Bibtex]
    @InProceedings{Wieseke:13,
    author = {Wieseke, N and Lechner, M and Ludwig, M and Marz, M},
    title = {{POMAGO}: Multiple Genome-Wide Alignment Tool for Bacteria},
    booktitle = {{Proceedings of the 9th International Symposium on Bioinformatics Research and Applications (ISBRA 2013), Charlotte, NC, USA, May 20-22, 2013.}},
    year = {2013},
    editor = {Zhipeng Cai and Oliver Eulenstein and Daniel Janies and Daniel Schwartz},
    volume = {7875},
    number = {1},
    series = {Lecture Notes in Computer Science},
    pages = {pp 249-260},
    publisher = {Springer},
    doi = {10.1007/978-3-642-38036-5_25},
    }

2012

  • [DOI] M. Dilcher, L. Hasib, M. Lechner, N. Wieseke, M. Middendorf, M. Marz, A. Koch, M. Spiegel, G. Dobler, F. T. Hufert, and M. Weidmann, "Genetic characterization of Tribeč virus and Kemerovo virus, two tick-transmitted human-pathogenic Orbiviruses," Virology, vol. 423, p. 68–76, 2012.
    [Bibtex]
    @Article{Dilcher:12,
    author = {Dilcher, Meik and Hasib, Lekbira and Lechner, Marcus and Wieseke, Nicolas and Middendorf, Martin and Marz, Manja and Koch, Andrea and Spiegel, Martin and Dobler, Gerhard and Hufert, Frank T and Weidmann, Manfred},
    title = {Genetic characterization of {T}ribe\v{c} virus and {K}emerovo virus, two tick-transmitted human-pathogenic {O}rbiviruses},
    journal = {{Virology}},
    year = {2012},
    volume = {423},
    pages = {68--76},
    abstract = {We determined the complete genome sequences of Tribeč virus (TRBV) and Kemerovo virus (KEMV), two tick-transmitted Orbiviruses that can cause diseases of the central nervous system and that are currently classified into the Great Island virus serogroup. VP2 proteins of TRBV and KEMV show very low sequence similarity to the homologous VP4 protein of tick-transmitted Great Island virus (GIV). The new sequence data support previous serological classification of these Orbiviruses into the Kemerovo serogroup, which is different from the Great Island virus serogroup. Genome segment 9 of TRBV and KEMV encodes several overlapping ORF's in the +1 reading frame relative to VP6(Hel). A co-phylogenetic analysis indicates a host switch from insect-borne Orbiviruses toward Ixodes species, which is in disagreement with previously published data.},
    doi = {10.1016/j.virol.2011.11.020},
    issue = {1},
    keywords = {Amino Acid Sequence; Animals; Arachnid Vectors, virology; Base Sequence; Cell Line; Evolution, Molecular; Genome, Viral; Humans; Molecular Sequence Data; Orbivirus, chemistry, classification, genetics, isolation & purification; Phylogeny; Reoviridae Infections, virology; Sequence Alignment; Ticks, virology; Viral Proteins, chemistry, genetics},
    pmid = {22189211},
    }
  • [DOI] B. M. Beckmann, P. G. Hoch, M. Marz, D. K. Willkomm, M. Salas, and R. K. Hartmann, "A pRNA-induced structural rearrangement triggers 6S-1 RNA release from RNA polymerase in Bacillus subtilis," EMBO J, vol. 31, p. 1727–1738, 2012.
    [Bibtex]
    @Article{Beckmann:12,
    author = {Beckmann, Benedikt M and Hoch, Philipp G and Marz, Manja and Willkomm, Dagmar K and Salas, Margarita and Hartmann, Roland K},
    title = {A p{RNA}-induced structural rearrangement triggers {6S-1 RNA} release from {RNA} polymerase in {B}acillus subtilis},
    journal = {{EMBO J}},
    year = {2012},
    volume = {31},
    pages = {1727--1738},
    abstract = {Bacillus subtilis 6S-1 RNA binds to the housekeeping RNA polymerase (σ(A)-RNAP) and directs transcription of short 'product' RNAs (pRNAs). Here, we demonstrate that once newly synthesized pRNAs form a sufficiently stable duplex with 6S-1 RNA, a structural rearrangement is induced in cis, which involves base-pairing between sequences in the 5'-portion of the central bulge and nucleotides that become available as a result of pRNA invasion. The rearrangement decreases 6S-1 RNA affinity for σ(A)-RNAP. Among the pRNA length variants synthesized by σ(A)-RNAP (up to ∼14 nt), only the longer ones, such as 12-14-mers, form a duplex with 6S-1 RNA that is sufficiently long-lived to induce the rearrangement. Yet, an LNA (locked nucleic acid) 8-mer can induce the same rearrangement due to conferring increased duplex stability. We propose that an interplay of rate constants for polymerization (k(pol)), for pRNA:6S-1 RNA hybrid duplex dissociation (k(off)) and for the rearrangement (k(conf)) determines whether pRNAs dissociate or rearrange 6S-1 structure to trigger 6S-1 RNA release from σ(A)-RNAP. A bioinformatic screen suggests that essentially all bacterial 6S RNAs have the potential to undergo a pRNA-induced structural rearrangement.},
    doi = {10.1038/emboj.2012.23},
    issue = {7},
    keywords = {Bacillus subtilis, metabolism; Base Sequence; DNA-Directed RNA Polymerases, chemistry, metabolism; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Bacterial, chemistry, metabolism; RNA, Untranslated},
    pmid = {22333917},
    }

2011

  • [DOI] M. Marz, A. R. Gruber, C. Höner Zu Siederdissen, F. Amman, S. Badelt, S. Bartschat, S. H. Bernhart, W. Beyer, S. Kehr, R. Lorenz, A. Tanzer, D. Yusuf, H. Tafer, I. L. Hofacker, and P. F. Stadler, "Animal snoRNAs and scaRNAs with exceptional structures," RNA Biol, vol. 8, p. 938–946, 2011.
    [Bibtex]
    @Article{Marz:11,
    author = {Marz, Manja and Gruber, Andreas R and H\"{o}ner Zu Siederdissen, Christian and Amman, Fabian and Badelt, Stefan and Bartschat, Sebastian and Bernhart, Stephan H and Beyer, Wolfgang and Kehr, Stephanie and Lorenz, Ronny and Tanzer, Andrea and Yusuf, Dilmurat and Tafer, Hakim and Hofacker, Ivo L and Stadler, Peter F},
    title = {Animal sno{RNA}s and sca{RNA}s with exceptional structures},
    journal = {{RNA Biol}},
    year = {2011},
    volume = {8},
    pages = {938--946},
    abstract = {The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly defined classes characterized by distinctive secondary structures and sequence motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or both classes of snoRNAs but differs substantially from the norm in some respects. Here, we compile the available information on these exceptional cases, conduct a thorough homology search throughout the available metazoan genomes, provide improved and expanded alignments, and investigate the evolutionary histories of these ncRNA families as well as their mutual relationships.},
    doi = {10.4161/rna.8.6.16603},
    issue = {6},
    keywords = {Animals; Base Sequence; Coiled Bodies, metabolism; Genome, genetics; Humans; Molecular Sequence Data; Nucleic Acid Conformation; Phylogeny; RNA, Small Nucleolar, chemistry, classification, genetics; Sequence Alignment, methods; Sequence Homology, Nucleic Acid},
    pmid = {21955586},
    }
  • [DOI] A. Bateman, S. Agrawal, E. Birney, E. A. Bruford, J. M. Bujnicki, G. Cochrane, J. R. Cole, M. E. Dinger, A. J. Enright, P. P. Gardner, D. Gautheret, S. Griffiths-Jones, J. Harrow, J. Herrero, I. H. Holmes, H. Huang, K. A. Kelly, P. Kersey, A. Kozomara, T. M. Lowe, M. Marz, S. Moxon, K. D. Pruitt, T. Samuelsson, P. F. Stadler, A. J. Vilella, J. Vogel, K. P. Williams, M. W. Wright, and C. Zwieb, "RNAcentral: a vision for an international database of RNA sequences," RNA, vol. 17, p. 1941–1946, 2011.
    [Bibtex]
    @Article{Bateman:11,
    author = {Bateman, Alex and Agrawal, Shipra and Birney, Ewan and Bruford, Elspeth A and Bujnicki, Janusz M and Cochrane, Guy and Cole, James R and Dinger, Marcel E and Enright, Anton J and Gardner, Paul P and Gautheret, Daniel and Griffiths-Jones, Sam and Harrow, Jen and Herrero, Javier and Holmes, Ian H and Huang, Hsien-Da and Kelly, Krystyna A and Kersey, Paul and Kozomara, Ana and Lowe, Todd M and Marz, Manja and Moxon, Simon and Pruitt, Kim D and Samuelsson, Tore and Stadler, Peter F and Vilella, Albert J and Vogel, Jan-Hinnerk and Williams, Kelly P and Wright, Mathew W and Zwieb, Christian},
    title = {{RNAcentral}: A vision for an international database of {RNA} sequences},
    journal = {{RNA}},
    year = {2011},
    volume = {17},
    pages = {1941--1946},
    abstract = {During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor.},
    doi = {10.1261/rna.2750811},
    issue = {11},
    keywords = {Animals; Base Sequence; Databases, Nucleic Acid; Humans; RNA, chemistry},
    pmid = {21940779},
    }
  • [DOI] M. Marz and P. F. Stadler, "RNA interactions," Adv Exp Med Biol, vol. 722, p. 20–38, 2011.
    [Bibtex]
    @Article{Marz:11a,
    author = {Marz, Manja and Stadler, Peter F},
    title = {{RNA} interactions},
    journal = {{Adv Exp Med Biol}},
    year = {2011},
    volume = {722},
    pages = {20--38},
    abstract = {Noncoding RNAs form an indispensible component of the cellular information processing networks, a role that crucially depends on the specificity of their interactions among each other as well as with DNA and protein. Patterns of intramolecular and intermolecular base pairs govern most RNA interactions. Specific base pairs dominate the structure formation of nucleic acids. Only little details distinguish intramolecular secondary structures from those cofolding molecules. RNA-protein interactions, on the other hand, are strongly dependent on the RNA structure as well since the sequence content of helical regions is largely unreadable, so that sequence specificity is mostly restricted to unpaired loop regions. Conservation of both sequence and structure thus this can give indications of the functioning of the diversity of ncRNAs.},
    doi = {10.1007/978-1-4614-0332-6_2},
    keywords = {Animals; Base Pairing, genetics; Base Sequence; DNA, chemistry, genetics, metabolism; Humans; Models, Genetic; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; RNA, chemistry, genetics, metabolism; RNA, Bacterial, chemistry, genetics, metabolism; RNA, Untranslated, chemistry, genetics, metabolism; RNA-Binding Proteins, chemistry, metabolism; Ribonucleoproteins, chemistry, metabolism},
    pmid = {21915780},
    }
  • [DOI] M. Lechner, S. Findeiss, L. Steiner, M. Marz, P. F. Stadler, and S. J. Prohaska, "Proteinortho: detection of (co-)orthologs in large-scale analysis," BMC Bioinf, vol. 12, p. 124, 2011.
    [Bibtex]
    @Article{Lechner:11,
    author = {Lechner, Marcus and Findeiss, Sven and Steiner, Lydia and Marz, Manja and Stadler, Peter F and Prohaska, Sonja J},
    title = {Proteinortho: detection of (co-)orthologs in large-scale analysis},
    journal = {{BMC Bioinf}},
    year = {2011},
    volume = {12},
    pages = {124},
    abstract = {Orthology analysis is an important part of data analysis in many areas of bioinformatics such as comparative genomics and molecular phylogenetics. The ever-increasing flood of sequence data, and hence the rapidly increasing number of genomes that can be compared simultaneously, calls for efficient software tools as brute-force approaches with quadratic memory requirements become infeasible in practise. The rapid pace at which new data become available, furthermore, makes it desirable to compute genome-wide orthology relations for a given dataset rather than relying on relations listed in databases. The program Proteinortho described here is a stand-alone tool that is geared towards large datasets and makes use of distributed computing techniques when run on multi-core hardware. It implements an extended version of the reciprocal best alignment heuristic. We apply Proteinortho to compute orthologous proteins in the complete set of all 717 eubacterial genomes available at NCBI at the beginning of 2009. We identified thirty proteins present in 99% of all bacterial proteomes. Proteinortho significantly reduces the required amount of memory for orthology analysis compared to existing tools, allowing such computations to be performed on off-the-shelf hardware.},
    doi = {10.1186/1471-2105-12-124},
    keywords = {Base Sequence; Databases, Genetic; Genomics, methods; Phylogeny; Sequence Alignment, methods; Software},
    pmid = {21526987},
    }
  • [DOI] A. X. Li, M. Marz, J. Qin, and C. M. Reidys, "RNA-RNA interaction prediction based on multiple sequence alignments," Bioinformatics, vol. 27, p. 456–463, 2011.
    [Bibtex]
    @Article{Li:11,
    author = {Li, Andrew X and Marz, Manja and Qin, Jing and Reidys, Christian M},
    title = {{RNA-RNA} interaction prediction based on multiple sequence alignments},
    journal = {Bioinformatics},
    year = {2011},
    volume = {27},
    pages = {456--463},
    abstract = {Many computerized methods for RNA-RNA interaction structure prediction have been developed. Recently, O(N(6)) time and O(N(4)) space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes. However, few of these methods incorporate the knowledge concerning related sequences, thus relevant evolutionary information is often neglected from the structure determination. Therefore, it is of considerable practical interest to introduce a method taking into consideration both: thermodynamic stability as well as sequence/structure covariation. We present the a priori folding algorithm ripalign, whose input consists of two (given) multiple sequence alignments (MSA). ripalign outputs (i) the partition function, (ii) base pairing probabilities, (iii) hybrid probabilities and (iv) a set of Boltzmann-sampled suboptimal structures consisting of canonical joint structures that are compatible to the alignments. Compared to the single sequence-pair folding algorithm rip, ripalign requires negligible additional memory resource but offers much better sensitivity and specificity, once alignments of suitable quality are given. ripalign additionally allows to incorporate structure constraints as input parameters. The algorithm described here is implemented in C as part of the rip package.},
    doi = {10.1093/bioinformatics/btq659},
    issue = {4},
    keywords = {Algorithms; Base Pairing; Base Sequence; Models, Statistical; Molecular Sequence Data; RNA, chemistry, genetics; Sequence Alignment, methods; Sequence Analysis, RNA, methods},
    pmid = {21134894},
    }

2010

  • [DOI] R. A. Dalloul, J. A. Long, A. V. Zimin, L. Aslam, K. Beal, L. A. Blomberg, P. Bouffard, D. W. Burt, O. Crasta, R. P. M. A. Crooijmans, K. Cooper, R. A. Coulombe, S. De, M. E. Delany, J. B. Dodgson, J. J. Dong, C. Evans, K. M. Frederickson, P. Flicek, L. Florea, O. Folkerts, M. A. M. Groenen, T. T. Harkins, J. Herrero, S. Hoffmann, H. Megens, A. Jiang, P. de Jong, P. Kaiser, H. Kim, K. Kim, S. Kim, D. Langenberger, M. Lee, T. Lee, S. Mane, G. Marcais, M. Marz, A. P. McElroy, T. Modise, M. Nefedov, C. Notredame, I. R. Paton, W. S. Payne, G. Pertea, D. Prickett, D. Puiu, D. Qioa, E. Raineri, M. Ruffier, S. L. Salzberg, M. C. Schatz, C. Scheuring, C. J. Schmidt, S. Schroeder, S. M. J. Searle, E. J. Smith, J. Smith, T. S. Sonstegard, P. F. Stadler, H. Tafer, Z. J. Tu, C. P. Van Tassell, A. J. Vilella, K. P. Williams, J. A. Yorke, L. Zhang, H. Zhang, X. Zhang, Y. Zhang, and K. M. Reed, "Multi-platform next-generation sequencing of the domestic turkey (Meleagris gallopavo): genome assembly and analysis," PLoS Biol, vol. 8, 2010.
    [Bibtex]
    @Article{Dalloul:10,
    author = {Dalloul, Rami A and Long, Julie A and Zimin, Aleksey V and Aslam, Luqman and Beal, Kathryn and Blomberg, Le Ann and Bouffard, Pascal and Burt, David W and Crasta, Oswald and Crooijmans, Richard P M A and Cooper, Kristal and Coulombe, Roger A and De, Supriyo and Delany, Mary E and Dodgson, Jerry B and Dong, Jennifer J and Evans, Clive and Frederickson, Karin M and Flicek, Paul and Florea, Liliana and Folkerts, Otto and Groenen, Martien A M and Harkins, Tim T and Herrero, Javier and Hoffmann, Steve and Megens, Hendrik-Jan and Jiang, Andrew and de Jong, Pieter and Kaiser, Pete and Kim, Heebal and Kim, Kyu-Won and Kim, Sungwon and Langenberger, David and Lee, Mi-Kyung and Lee, Taeheon and Mane, Shrinivasrao and Marcais, Guillaume and Marz, Manja and McElroy, Audrey P and Modise, Thero and Nefedov, Mikhail and Notredame, Cédric and Paton, Ian R and Payne, William S and Pertea, Geo and Prickett, Dennis and Puiu, Daniela and Qioa, Dan and Raineri, Emanuele and Ruffier, Magali and Salzberg, Steven L and Schatz, Michael C and Scheuring, Chantel and Schmidt, Carl J and Schroeder, Steven and Searle, Stephen M J and Smith, Edward J and Smith, Jacqueline and Sonstegard, Tad S and Stadler, Peter F and Tafer, Hakim and Tu, Zhijian Jake and Van Tassell, Curtis P and Vilella, Albert J and Williams, Kelly P and Yorke, James A and Zhang, Liqing and Zhang, Hong-Bin and Zhang, Xiaojun and Zhang, Yang and Reed, Kent M},
    title = {Multi-platform next-generation sequencing of the domestic turkey ({M}eleagris gallopavo): genome assembly and analysis},
    journal = {{PLoS Biol}},
    year = {2010},
    volume = {8},
    abstract = {A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (∼1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.},
    doi = {10.1371/journal.pbio.1000475},
    issue = {9},
    keywords = {Animals; Base Sequence; Chromosome Mapping; DNA, genetics; Genome; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Species Specificity; Turkeys, genetics},
    pmid = {20838655},
    }
  • [DOI] D. Yusuf, M. Marz, P. F. Stadler, and I. L. Hofacker, "Bcheck: a wrapper tool for detecting RNase P RNA genes," BMC Genomics, vol. 11, p. 432, 2010.
    [Bibtex]
    @Article{Yusuf:10,
    author = {Yusuf, Dilmurat and Marz, Manja and Stadler, Peter F and Hofacker, Ivo L},
    title = {Bcheck: a wrapper tool for detecting {RNase P} {RNA} genes},
    journal = {{BMC Genomics}},
    year = {2010},
    volume = {11},
    pages = {432},
    abstract = {Effective bioinformatics solutions are needed to tackle challenges posed by industrial-scale genome annotation. We present Bcheck, a wrapper tool which predicts RNase P RNA genes by combining the speed of pattern matching and sensitivity of covariance models. The core of Bcheck is a library of subfamily specific descriptor models and covariance models. Scanning all microbial genomes in GenBank identifies RNase P RNA genes in 98% of 1024 microbial chromosomal sequences within just 4 hours on single CPU. Comparing to existing annotations found in 387 of the GenBank files, Bcheck predictions have more intact structure and are automatically classified by subfamily membership. For eukaryotic chromosomes Bcheck could identify the known RNase P RNA genes in 84 out of 85 metazoan genomes and 19 out of 21 fungi genomes. Bcheck predicted 37 novel eukaryotic RNase P RNA genes, 32 of which are from fungi. Gene duplication events are observed in at least 20 metazoan organisms. Scanning of meta-genomic data from the Global Ocean Sampling Expedition, comprising over 10 million sample sequences (18 Gigabases), predicted 2909 unique genes, 98% of which fall into ancestral bacteria A type of RNase P RNA and 66% of which have no close homolog to known prokaryotic RNase P RNA. The combination of efficient filtering by means of a descriptor-based search and subsequent construction of a high-quality gene model by means of a covariance model provides an efficient method for the detection of RNase P RNA genes in large-scale sequencing data. Bcheck is implemented as webserver and can also be downloaded for local use from http://rna.tbi.univie.ac.at/bcheck.},
    doi = {10.1186/1471-2164-11-432},
    keywords = {Algorithms; Amino Acid Sequence; Animals; Base Sequence; Computational Biology; Databases, Genetic; Internet; Metagenomics; Models, Genetic; Molecular Sequence Data; RNA, genetics; Ribonuclease P, chemistry, genetics; Software},
    pmid = {20626900},
    }
  • M. Marz, N. Vanzo, and P. F. Stadler, "Temperature-dependent structural variability of RNAs: spliced leader RNAs and their evolutionary history," J Bioinform Comput Biol, vol. 8, p. 1–17, 2010.
    [Bibtex]
    @Article{Marz:10,
    author = {Marz, Manja and Vanzo, Nathalie and Stadler, Peter F},
    title = {Temperature-dependent structural variability of {RNA}s: spliced leader {RNA}s and their evolutionary history},
    journal = {{J Bioinform Comput Biol}},
    year = {2010},
    volume = {8},
    pages = {1--17},
    abstract = {The structures attained by RNA molecules depend not only on their sequence but also on environmental parameters such as their temperature. So far, this effect has been largely neglected in bioinformatics studies. Here, we show that structural comparisons can be facilitated and more coherent structural models can be obtained when differences in environmental parameters are taken into account. We re-evaluate the secondary structures of the spliced leader (SL) RNAs from the seven eukaryotic phyla in which SL RNA trans-splicing has been described. Adjusting structure prediction to the natural growth temperatures and considering energetically similar secondary structures, we observe striking similarities among Euglenida, Kinetoplastida, Dinophyceae, Cnidaria, Rotifera, Nematoda, Platyhelminthes, and Tunicata that cannot be explained easily by the independent innovation of SL RNAs in each of these phyla. Supplementary Table is available at http://www.worldscinet.com/jbcb/.},
    issue = {1},
    keywords = {Algorithms; Animals; Base Sequence; Computational Biology; Eukaryota; Evolution, Molecular; Humans; Models, Biological; Nucleic Acid Conformation; Phylogeny; RNA Splicing; RNA, Spliced Leader, chemistry, genetics; Sequence Homology, Nucleic Acid; Temperature; Thermodynamics},
    pmid = {20183871},
    }

2009

  • [DOI] M. Marz, A. Donath, N. Verstraete, V. T. Nguyen, P. F. Stadler, and O. Bensaude, "Evolution of 7SK RNA and its protein partners in metazoa," Mol Biol Evol, vol. 26, p. 2821–2830, 2009.
    [Bibtex]
    @Article{Marz:09,
    author = {Marz, Manja and Donath, Alexander and Verstraete, Nina and Nguyen, Van Trung and Stadler, Peter F and Bensaude, Olivier},
    title = {Evolution of {7SK} {RNA} and its protein partners in metazoa},
    journal = {{Mol Biol Evol}},
    year = {2009},
    volume = {26},
    pages = {2821--2830},
    abstract = {7SK RNA is a key player in the regulation of polymerase II transcription. 7SK RNA was considered as a highly conserved vertebrate innovation. The discovery of poorly conserved homologs in several insects and lophotrochozoans, however, implies a much earlier evolutionary origin. The mechanism of 7SK function requires interaction with the proteins HEXIM and La-related protein 7. Here, we present a comprehensive computational analysis of these two proteins in metazoa, and we extend the collection of 7SK RNAs by several additional candidates. In particular, we describe 7SK homologs in Caenorhabditis species. Furthermore, we derive an improved secondary structure model of 7SK RNA, which shows that the structure is quite well-conserved across animal phyla despite the extreme divergence at sequence level.},
    doi = {10.1093/molbev/msp198},
    issue = {12},
    keywords = {Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans, genetics; Consensus Sequence; Evolution, Molecular; Humans; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Phylogeny; RNA, Small Nuclear, chemistry, genetics; RNA-Binding Proteins, chemistry, genetics; Sequence Alignment; Sequence Homology, Nucleic Acid},
    pmid = {19734296},
    }
  • M. Marz and P. F. Stadler, "Comparative analysis of eukaryotic U3 snoRNA," RNA Biol, vol. 6, p. 503–507, 2009.
    [Bibtex]
    @Article{Marz:09a,
    author = {Marz, Manja and Stadler, Peter F},
    title = {Comparative analysis of eukaryotic {U3} sno{RNA}},
    journal = {{RNA Biol}},
    year = {2009},
    volume = {6},
    pages = {503--507},
    abstract = {The U3 snoRNA is an exceptional box C/D snoRNA, which is involved in pre-rRNA processing without directing chemical modifications. We report here on a comprehensive computational survey resulting in U3 sequences for more than 90 additional eukaryotes. This extended data basis is used to improve the secondary structure models. The detailed investigation of the structural variation of U3 snoRNAs turns out to be much more extensive than previously thought. Many fungal U3 genes, in addition, contain introns. U3 promoters are snRNA-like but show substantial variations even between related species.},
    issue = {5},
    keywords = {Base Sequence; Computational Biology, methods; Eukaryota, genetics; Genetic Variation; Introns; Nucleic Acid Conformation; RNA, Small Nucleolar, chemistry, genetics},
    pmid = {19875933},
    }
  • [DOI] C. S. Copeland, M. Marz, D. Rose, J. Hertel, P. J. Brindley, C. B. Santana, S. Kehr, C. S. Attolini, and P. F. Stadler, "Homology-based annotation of non-coding RNAs in the genomes of Schistosoma mansoni and Schistosoma japonicum," BMC Genomics, vol. 10, p. 464, 2009.
    [Bibtex]
    @Article{Copeland:09,
    author = {Copeland, Claudia S and Marz, Manja and Rose, Dominic and Hertel, Jana and Brindley, Paul J and Santana, Clara Bermudez and Kehr, Stephanie and Attolini, Camille Stephan-Otto and Stadler, Peter F},
    title = {Homology-based annotation of non-coding {RNA}s in the genomes of {S}chistosoma mansoni and {S}chistosoma japonicum},
    journal = {{BMC Genomics}},
    year = {2009},
    volume = {10},
    pages = {464},
    abstract = {Schistosomes are trematode parasites of the phylum Platyhelminthes. They are considered the most important of the human helminth parasites in terms of morbidity and mortality. Draft genome sequences are now available for Schistosoma mansoni and Schistosoma japonicum. Non-coding RNA (ncRNA) plays a crucial role in gene expression regulation, cellular function and defense, homeostasis, and pathogenesis. The genome-wide annotation of ncRNAs is a non-trivial task unless well-annotated genomes of closely related species are already available. A homology search for structured ncRNA in the genome of S. mansoni resulted in 23 types of ncRNAs with conserved primary and secondary structure. Among these, we identified rRNA, snRNA, SL RNA, SRP, tRNAs and RNase P, and also possibly MRP and 7SK RNAs. In addition, we confirmed five miRNAs that have recently been reported in S. japonicum and found two additional homologs of known miRNAs. The tRNA complement of S. mansoni is comparable to that of the free-living planarian Schmidtea mediterranea, although for some amino acids differences of more than a factor of two are observed: Leu, Ser, and His are overrepresented, while Cys, Meth, and Ile are underrepresented in S. mansoni. On the other hand, the number of tRNAs in the genome of S. japonicum is reduced by more than a factor of four. Both schistosomes have a complete set of minor spliceosomal snRNAs. Several ncRNAs that are expected to exist in the S. mansoni genome were not found, among them the telomerase RNA, vault RNAs, and Y RNAs. The ncRNA sequences and structures presented here represent the most complete dataset of ncRNA from any lophotrochozoan reported so far. This data set provides an important reference for further analysis of the genomes of schistosomes and indeed eukaryotic genomes at large.},
    doi = {10.1186/1471-2164-10-464},
    keywords = {Animals; Base Sequence; Conserved Sequence; Genome, Helminth; MicroRNAs, genetics; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Helminth, genetics; RNA, Ribosomal, genetics; RNA, Small Nucleolar, genetics; RNA, Spliced Leader, genetics; RNA, Transfer, genetics; RNA, Untranslated, genetics; Schistosoma japonicum, genetics; Schistosoma mansoni, genetics; Sequence Alignment; Sequence Analysis, RNA; Sequence Homology, Nucleic Acid},
    pmid = {19814823},
    }
  • T. Ingalls, G. Martius, M. Marz, and S. J. Prohaska, "Converting DNA to music: ComposAlign," in Proceedings of the German Conference on Bioinformatics (GCB 2009), 2009, pp. 93-104.
    [Bibtex]
    @InProceedings{Ingalls:09,
    author = {T. Ingalls and G. Martius and M. Marz and S. J. Prohaska},
    title = {Converting {DNA} to music: {ComposAlign}},
    booktitle = {{Proceedings of the German Conference on Bioinformatics (GCB 2009)}},
    year = {2009},
    volume = {P-157},
    series = {GI Lecture Notes in Informatics},
    pages = {93-104},
    }
  • [DOI] M. Hiller, S. Findeiss, S. Lein, M. Marz, C. Nickel, D. Rose, C. Schulz, R. Backofen, S. J. Prohaska, G. Reuter, and P. F. Stadler, "Conserved introns reveal novel transcripts in Drosophila melanogaster," Genome Res, vol. 19, p. 1289–1300, 2009.
    [Bibtex]
    @Article{Hiller:09,
    author = {Hiller, Michael and Findeiss, Sven and Lein, Sandro and Marz, Manja and Nickel, Claudia and Rose, Dominic and Schulz, Christine and Backofen, Rolf and Prohaska, Sonja J and Reuter, Gunter and Stadler, Peter F},
    title = {Conserved introns reveal novel transcripts in {D}rosophila melanogaster},
    journal = {{Genome Res}},
    year = {2009},
    volume = {19},
    pages = {1289--1300},
    abstract = {Noncoding RNAs that are-like mRNAs-spliced, capped, and polyadenylated have important functions in cellular processes. The inventory of these mRNA-like noncoding RNAs (mlncRNAs), however, is incomplete even in well-studied organisms, and so far, no computational methods exist to predict such RNAs from genomic sequences only. The subclass of these transcripts that is evolutionarily conserved usually has conserved intron positions. We demonstrate here that a genome-wide comparative genomics approach searching for short conserved introns is capable of identifying conserved transcripts with a high specificity. Our approach requires neither an open reading frame nor substantial sequence or secondary structure conservation in the surrounding exons. Thus it identifies spliced transcripts in an unbiased way. After applying our approach to insect genomes, we predict 369 introns outside annotated coding transcripts, of which 131 are confirmed by expressed sequence tags (ESTs) and/or noncoding FlyBase transcripts. Of the remaining 238 novel introns, about half are associated with protein-coding genes-either extending coding or untranslated regions or likely belonging to unannotated coding genes. The remaining 129 introns belong to novel mlncRNAs that are largely unstructured. Using RT-PCR, we verified seven of 12 tested introns in novel mlncRNAs and 11 of 17 introns in novel coding genes. The expression level of all verified mlncRNA transcripts is low but varies during development, which suggests regulation. As conserved introns indicate both purifying selection on the exon-intron structure and conserved expression of the transcript in related species, the novel mlncRNAs are good candidates for functional transcripts.},
    doi = {10.1101/gr.090050.108},
    issue = {7},
    keywords = {Animals; Base Sequence; Computational Biology; Drosophila melanogaster, genetics; Exons, genetics; Expressed Sequence Tags; Female; Genes, Insect; Introns, genetics; Male; Molecular Sequence Data; Open Reading Frames, genetics; RNA Splicing; RNA, Messenger; RNA, Untranslated, genetics; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid},
    pmid = {19458021},
    }
  • [DOI] J. Hertel, D. de Jong, M. Marz, D. Rose, H. Tafer, A. Tanzer, B. Schierwater, and P. F. Stadler, "Non-coding RNA annotation of the genome of Trichoplax adhaerens," Nucleic Acids Res, vol. 37, p. 1602–1615, 2009.
    [Bibtex]
    @Article{Hertel:09,
    author = {Hertel, Jana and de Jong, Danielle and Marz, Manja and Rose, Dominic and Tafer, Hakim and Tanzer, Andrea and Schierwater, Bernd and Stadler, Peter F},
    title = {Non-coding {RNA} annotation of the genome of {T}richoplax adhaerens},
    journal = {{Nucleic Acids Res}},
    year = {2009},
    volume = {37},
    pages = {1602--1615},
    abstract = {A detailed annotation of non-protein coding RNAs is typically missing in initial releases of newly sequenced genomes. Here we report on a comprehensive ncRNA annotation of the genome of Trichoplax adhaerens, the presumably most basal metazoan whose genome has been published to-date. Since blast identified only a small fraction of the best-conserved ncRNAs--in particular rRNAs, tRNAs and some snRNAs--we developed a semi-global dynamic programming tool, GotohScan, to increase the sensitivity of the homology search. It successfully identified the full complement of major and minor spliceosomal snRNAs, the genes for RNase P and MRP RNAs, the SRP RNA, as well as several small nucleolar RNAs. We did not find any microRNA candidates homologous to known eumetazoan sequences. Interestingly, most ncRNAs, including the pol-III transcripts, appear as single-copy genes or with very small copy numbers in the Trichoplax genome.},
    doi = {10.1093/nar/gkn1084},
    issue = {5},
    keywords = {Animals; Base Sequence; Endoribonucleases, chemistry; Genome; MicroRNAs, chemistry; Molecular Sequence Data; Nucleic Acid Conformation; Placozoa, genetics; RNA, Ribosomal, genetics; RNA, Small Cytoplasmic, chemistry; RNA, Small Nuclear, chemistry, genetics; RNA, Small Nucleolar, chemistry, genetics; RNA, Transfer, genetics; RNA, Untranslated, genetics; Ribonuclease P, genetics; Signal Recognition Particle, chemistry; Software},
    pmid = {19151082},
    }
  • T. A. Jones, W. Otto, M. Marz, S. R. Eddy, and P. F. Stadler, "A survey of nematode SmY RNAs," RNA Biol, vol. 6, p. 5–8, 2009.
    [Bibtex]
    @Article{Jones:09,
    author = {Jones, Thomas A and Otto, Wolfgang and Marz, Manja and Eddy, Sean R and Stadler, Peter F},
    title = {A survey of nematode {SmY} {RNAs}},
    journal = {{RNA Biol}},
    year = {2009},
    volume = {6},
    pages = {5--8},
    abstract = {SmY RNAs are a family of approximately 70-90 nt small nuclear RNAs found in nematodes. In C. elegans, SmY RNAs copurify in a small ribonucleoprotein (snRNP) complex related to the SL1 and SL2 snRNPs that are involved in nematode mRNA trans-splicing. Here we describe a comprehensive computational analysis of SmY RNA homologs found in the currently available genome sequences. We identify homologs in all sequenced nematode genomes in class Chromadorea. We are unable to identify homologs in a more distantly related nematode species, Trichinella spiralis (class: Dorylaimia), and in representatives of non-nematode phyla that use trans-splicing. Using comparative RNA sequence analysis, we infer a conserved consensus SmY RNA secondary structure consisting of two stems flanking a consensus Sm protein binding site. A representative seed alignment of the SmY RNA family, annotated with the inferred consensus secondary structure, has been deposited with the Rfam RNA families database.},
    issue = {1},
    keywords = {Animals; Base Sequence; Binding Sites; Caenorhabditis elegans; Genome; Molecular Sequence Data; Nematoda, genetics; Nucleic Acid Conformation; Phylogeny; RNA, metabolism; RNA, Small Nuclear, metabolism; Trichinella spiralis; snRNP Core Proteins, chemistry},
    pmid = {19106623},
    }

2008

  • [DOI] M. Marz, T. Kirsten, and P. F. Stadler, "Evolution of spliceosomal snRNA genes in metazoan animals," J Mol Evol, vol. 67, p. 594–607, 2008.
    [Bibtex]
    @Article{Marz:08,
    author = {Marz, Manuela and Kirsten, Toralf and Stadler, Peter F},
    title = {Evolution of spliceosomal sn{RNA} genes in metazoan animals},
    journal = {{J Mol Evol}},
    year = {2008},
    volume = {67},
    pages = {594--607},
    abstract = {While studies of the evolutionary histories of protein families are commonplace, little is known on noncoding RNAs beyond microRNAs and some snoRNAs. Here we investigate in detail the evolutionary history of the nine spliceosomal snRNA families (U1, U2, U4, U5, U6, U11, U12, U4atac, and U6atac) across the completely or partially sequenced genomes of metazoan animals. Representatives of the five major spliceosomal snRNAs were found in all genomes. None of the minor splicesomal snRNAs were detected in nematodes or in the shotgun traces of Oikopleura dioica, while in all other animal genomes at most one of them is missing. Although snRNAs are present in multiple copies in most genomes, distinguishable paralogue groups are not stable over long evolutionary times, although they appear independently in several clades. In general, animal snRNA secondary structures are highly conserved, albeit, in particular, U11 and U12 in insects exhibit dramatic variations. An analysis of genomic context of snRNAs reveals that they behave like mobile elements, exhibiting very little syntenic conservation.},
    doi = {10.1007/s00239-008-9149-6},
    issue = {6},
    keywords = {Animals; Base Sequence; Evolution, Molecular; Multigene Family, genetics; Nucleic Acid Conformation; Phylogeny; RNA, Small Nuclear, chemistry, genetics; Sequence Homology, Nucleic Acid; Spliceosomes, genetics},
    pmid = {19030770},
    }
  • [DOI] A. R. Gruber, D. Koper-Emde, M. Marz, H. Tafer, S. Bernhart, G. Obernosterer, A. Mosig, I. L. Hofacker, P. F. Stadler, and B. Benecke, "Invertebrate 7SK snRNAs," J Mol Evol, vol. 66, p. 107–115, 2008.
    [Bibtex]
    @Article{Gruber:08,
    author = {Gruber, Andreas R and Koper-Emde, Dorota and Marz, Manja and Tafer, Hakim and Bernhart, Stephan and Obernosterer, Gregor and Mosig, Axel and Hofacker, Ivo L and Stadler, Peter F and Benecke, Bernd-Joachim},
    title = {Invertebrate {7SK} sn{RNA}s},
    journal = {{J Mol Evol}},
    year = {2008},
    volume = {66},
    pages = {107--115},
    abstract = {7SK RNA is a highly abundant noncoding RNA in mammalian cells whose function in transcriptional regulation has only recently been elucidated. Despite its highly conserved sequence throughout vertebrates, all attempts to discover 7SK RNA homologues in invertebrate species have failed so far. Here we report on a combined experimental and computational survey that succeeded in discovering 7SK RNAs in most of the major deuterostome clades and in two protostome phyla: mollusks and annelids. Despite major efforts, no candidates were found in any of the many available ecdysozoan genomes, however. The additional sequence data confirm the evolutionary conservation and hence functional importance of the previously described 3' and 5' stem-loop motifs, and provide evidence for a third, structurally well-conserved domain.},
    doi = {10.1007/s00239-007-9052-6},
    issue = {2},
    keywords = {Animals; Base Sequence; Blotting, Northern; Cloning, Molecular; Evolution, Molecular; Humans; Invertebrates, genetics; Molecular Sequence Data; Nucleic Acid Conformation; Phylogeny; Promoter Regions, Genetic, genetics; RNA, Antisense, genetics; RNA, Small Nuclear, chemistry, genetics; Sequence Alignment; Vertebrates, genetics},
    pmid = {18193315},
    }

2007

  • [DOI] M. Marz, A. Mosig, B. M. R. Stadler, and P. F. Stadler, "U7 snRNAs: a computational survey," Genomics Proteomics Bioinformatics, vol. 5, p. 187–195, 2007.
    [Bibtex]
    @Article{Marz:07,
    author = {Marz, Manja and Mosig, Axel and Stadler, Bärbel M R and Stadler, Peter F},
    title = {{U7} sn{RNA}s: a computational survey},
    journal = {{Genomics Proteomics Bioinformatics}},
    year = {2007},
    volume = {5},
    pages = {187--195},
    abstract = {U7 small nuclear RNA (snRNA) sequences have been described only for a handful of animal species in the past. Here we describe a computational search for functional U7 snRNA genes throughout vertebrates including the upstream sequence elements characteristic for snRNAs transcribed by polymerase II. Based on the results of this search, we discuss the high variability of U7 snRNAs in both sequence and structure, and report on an attempt to find U7 snRNA sequences in basal deuterostomes and non-drosophilids insect genomes based on a combination of sequence, structure, and promoter features. Due to the extremely short sequence and the high variability in both sequence and structure, no unambiguous candidates were found. These results cast doubt on putative U7 homologs in even more distant organisms that are reported in the most recent release of the Rfam database.},
    doi = {10.1016/S1672-0229(08)60006-6},
    issue = {3-4},
    keywords = {Animals; Base Sequence; Databases, Nucleic Acid; Evolution, Molecular; Genomics, statistics & numerical data; Humans; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Small Nuclear, chemistry, genetics; Sequence Alignment; Species Specificity; Vertebrates, genetics},
    pmid = {18267300},
    }
  • [DOI] S. Washietl, J. S. Pedersen, J. O. Korbel, C. Stocsits, A. R. Gruber, J. Hackermüller, J. Hertel, M. Lindemeyer, K. Reiche, A. Tanzer, C. Ucla, C. Wyss, S. E. Antonarakis, F. Denoeud, J. Lagarde, J. Drenkow, P. Kapranov, T. R. Gingeras, R. Guigó, M. Snyder, M. B. Gerstein, A. Reymond, I. L. Hofacker, and P. F. Stadler, "Structured RNAs in the ENCODE selected regions of the human genome," Genome Res, vol. 17, p. 852–864, 2007.
    [Bibtex]
    @Article{Washietl:07,
    author = {Washietl, Stefan and Pedersen, Jakob S and Korbel, Jan O and Stocsits, Claudia and Gruber, Andreas R and Hackerm\"{u}ller, J\"{o}rg and Hertel, Jana and Lindemeyer, Manja and Reiche, Kristin and Tanzer, Andrea and Ucla, Catherine and Wyss, Carine and Antonarakis, Stylianos E and Denoeud, France and Lagarde, Julien and Drenkow, Jorg and Kapranov, Philipp and Gingeras, Thomas R and Guig\'{o}, Roderic and Snyder, Michael and Gerstein, Mark B and Reymond, Alexandre and Hofacker, Ivo L and Stadler, Peter F},
    title = {Structured {RNA}s in the {ENCODE} selected regions of the human genome},
    journal = {{Genome Res}},
    year = {2007},
    volume = {17},
    pages = {852--864},
    abstract = {Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic-stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to approximately 2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3'-UTRs. While we estimate a significant false discovery rate of approximately 50%-70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).},
    doi = {10.1101/gr.5650707},
    issue = {6},
    keywords = {3' Untranslated Regions, genetics; Base Sequence; GC Rich Sequence; Genome, Human; Humans; Molecular Sequence Data; Quantitative Trait Loci; RNA, Messenger, genetics; RNA, Untranslated, genetics; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic},
    pmid = {17568003},
    url = {https://www.tbi.univie.ac.at/papers/SUPPLEMENTS/ENCODE/},
    }
  • [DOI] ENCODE Project Consortium, E. Birney, J. A. Stamatoyannopoulos, A. Dutta, R. Guigó, T. R. Gingeras, E. H. Margulies, Z. Weng, M. Snyder, E. T. Dermitzakis, R. E. Thurman, M. S. Kuehn, C. M. Taylor, S. Neph, C. M. Koch, S. Asthana, A. Malhotra, I. Adzhubei, J. A. Greenbaum, R. M. Andrews, P. Flicek, P. J. Boyle, H. Cao, N. P. Carter, G. K. Clelland, S. Davis, N. Day, P. Dhami, S. C. Dillon, M. O. Dorschner, H. Fiegler, P. G. Giresi, J. Goldy, M. Hawrylycz, A. Haydock, R. Humbert, K. D. James, B. E. Johnson, E. M. Johnson, T. T. Frum, E. R. Rosenzweig, N. Karnani, K. Lee, G. C. Lefebvre, P. A. Navas, F. Neri, S. C. J. Parker, P. J. Sabo, R. Sandstrom, A. Shafer, D. Vetrie, M. Weaver, S. Wilcox, M. Yu, F. S. Collins, J. Dekker, J. D. Lieb, T. D. Tullius, G. E. Crawford, S. Sunyaev, W. S. Noble, I. Dunham, F. Denoeud, A. Reymond, P. Kapranov, J. Rozowsky, D. Zheng, R. Castelo, A. Frankish, J. Harrow, S. Ghosh, A. Sandelin, I. L. Hofacker, R. Baertsch, D. Keefe, S. Dike, J. Cheng, H. A. Hirsch, E. A. Sekinger, J. Lagarde, J. F. Abril, A. Shahab, C. Flamm, C. Fried, J. Hackermüller, J. Hertel, M. Lindemeyer, K. Missal, A. Tanzer, S. Washietl, J. Korbel, O. Emanuelsson, J. S. Pedersen, N. Holroyd, R. Taylor, D. Swarbreck, N. Matthews, M. C. Dickson, D. J. Thomas, M. T. Weirauch, J. Gilbert, J. Drenkow, I. Bell, X. Zhao, K. G. Srinivasan, W. Sung, H. S. Ooi, K. P. Chiu, S. Foissac, T. Alioto, M. Brent, L. Pachter, M. L. Tress, A. Valencia, S. W. Choo, C. Y. Choo, C. Ucla, C. Manzano, C. Wyss, E. Cheung, T. G. Clark, J. B. Brown, M. Ganesh, S. Patel, H. Tammana, J. Chrast, C. N. Henrichsen, C. Kai, J. Kawai, U. Nagalakshmi, J. Wu, Z. Lian, J. Lian, P. Newburger, X. Zhang, P. Bickel, J. S. Mattick, P. Carninci, Y. Hayashizaki, S. Weissman, T. Hubbard, R. M. Myers, J. Rogers, P. F. Stadler, T. M. Lowe, C. Wei, Y. Ruan, K. Struhl, M. Gerstein, S. E. Antonarakis, Y. Fu, E. D. Green, U. Karaöz, A. Siepel, J. Taylor, L. A. Liefer, K. A. Wetterstrand, P. J. Good, E. A. Feingold, M. S. Guyer, G. M. Cooper, G. Asimenos, C. N. Dewey, M. Hou, S. Nikolaev, J. I. Montoya-Burgos, A. Löytynoja, S. Whelan, F. Pardi, T. Massingham, H. Huang, N. R. Zhang, I. Holmes, J. C. Mullikin, A. Ureta-Vidal, B. Paten, M. Seringhaus, D. Church, K. Rosenbloom, J. W. Kent, E. A. Stone, NISC Comparative Sequencing Program, Baylor College of Medicine Human Genome Sequencing Center, Washington University Genome Sequencing Center, Broad Institute, Children's Hospital Oakland Research Institute, S. Batzoglou, N. Goldman, R. C. Hardison, D. Haussler, W. Miller, A. Sidow, N. D. Trinklein, Z. D. Zhang, L. Barrera, R. Stuart, D. C. King, A. Ameur, S. Enroth, M. C. Bieda, J. Kim, A. A. Bhinge, N. Jiang, J. Liu, F. Yao, V. B. Vega, C. W. H. Lee, P. Ng, A. Shahab, A. Yang, Z. Moqtaderi, Z. Zhu, X. Xu, S. Squazzo, M. J. Oberley, D. Inman, M. A. Singer, T. A. Richmond, K. J. Munn, A. Rada-Iglesias, O. Wallerman, J. Komorowski, J. C. Fowler, P. Couttet, A. W. Bruce, O. M. Dovey, P. D. Ellis, C. F. Langford, D. A. Nix, G. Euskirchen, S. Hartman, A. E. Urban, P. Kraus, S. Van Calcar, N. Heintzman, T. H. Kim, K. Wang, C. Qu, G. Hon, R. Luna, C. K. Glass, G. M. Rosenfeld, S. F. Aldred, S. J. Cooper, A. Halees, J. M. Lin, H. P. Shulha, X. Zhang, M. Xu, J. N. S. Haidar, Y. Yu, Y. Ruan, V. R. Iyer, R. D. Green, C. Wadelius, P. J. Farnham, B. Ren, R. A. Harte, A. S. Hinrichs, H. Trumbower, H. Clawson, J. Hillman-Jackson, A. S. Zweig, K. Smith, A. Thakkapallayil, G. Barber, R. M. Kuhn, D. Karolchik, L. Armengol, C. P. Bird, P. I. W. de Bakker, A. D. Kern, N. Lopez-Bigas, J. D. Martin, B. E. Stranger, A. Woodroffe, E. Davydov, A. Dimas, E. Eyras, I. B. Hallgrímsdóttir, J. Huppert, M. C. Zody, G. R. Abecasis, X. Estivill, G. G. Bouffard, X. Guan, N. F. Hansen, J. R. Idol, V. V. B. Maduro, B. Maskeri, J. C. McDowell, M. Park, P. J. Thomas, A. C. Young, R. W. Blakesley, D. M. Muzny, E. Sodergren, D. A. Wheeler, K. C. Worley, H. Jiang, G. M. Weinstock, R. A. Gibbs, T. Graves, R. Fulton, E. R. Mardis, R. K. Wilson, M. Clamp, J. Cuff, S. Gnerre, D. B. Jaffe, J. L. Chang, K. Lindblad-Toh, E. S. Lander, M. Koriabine, M. Nefedov, K. Osoegawa, Y. Yoshinaga, B. Zhu, and P. J. de Jong, "Identification and analysis of functional elements in 1\% of the human genome by the ENCODE pilot project," Nature, vol. 447, p. 799–816, 2007.
    [Bibtex]
    @Article{Consortium:07,
    author = {{ENCODE Project Consortium} and Birney, Ewan and Stamatoyannopoulos, John A and Dutta, Anindya and Guig\'{o}, Roderic and Gingeras, Thomas R and Margulies, Elliott H and Weng, Zhiping and Snyder, Michael and Dermitzakis, Emmanouil T and Thurman, Robert E and Kuehn, Michael S and Taylor, Christopher M and Neph, Shane and Koch, Christoph M and Asthana, Saurabh and Malhotra, Ankit and Adzhubei, Ivan and Greenbaum, Jason A and Andrews, Robert M and Flicek, Paul and Boyle, Patrick J and Cao, Hua and Carter, Nigel P and Clelland, Gayle K and Davis, Sean and Day, Nathan and Dhami, Pawandeep and Dillon, Shane C and Dorschner, Michael O and Fiegler, Heike and Giresi, Paul G and Goldy, Jeff and Hawrylycz, Michael and Haydock, Andrew and Humbert, Richard and James, Keith D and Johnson, Brett E and Johnson, Ericka M and Frum, Tristan T and Rosenzweig, Elizabeth R and Karnani, Neerja and Lee, Kirsten and Lefebvre, Gregory C and Navas, Patrick A and Neri, Fidencio and Parker, Stephen C J and Sabo, Peter J and Sandstrom, Richard and Shafer, Anthony and Vetrie, David and Weaver, Molly and Wilcox, Sarah and Yu, Man and Collins, Francis S and Dekker, Job and Lieb, Jason D and Tullius, Thomas D and Crawford, Gregory E and Sunyaev, Shamil and Noble, William S and Dunham, Ian and Denoeud, France and Reymond, Alexandre and Kapranov, Philipp and Rozowsky, Joel and Zheng, Deyou and Castelo, Robert and Frankish, Adam and Harrow, Jennifer and Ghosh, Srinka and Sandelin, Albin and Hofacker, Ivo L and Baertsch, Robert and Keefe, Damian and Dike, Sujit and Cheng, Jill and Hirsch, Heather A and Sekinger, Edward A and Lagarde, Julien and Abril, Josep F and Shahab, Atif and Flamm, Christoph and Fried, Claudia and Hackerm\"{u}ller, J\"{o}rg and Hertel, Jana and Lindemeyer, Manja and Missal, Kristin and Tanzer, Andrea and Washietl, Stefan and Korbel, Jan and Emanuelsson, Olof and Pedersen, Jakob S and Holroyd, Nancy and Taylor, Ruth and Swarbreck, David and Matthews, Nicholas and Dickson, Mark C and Thomas, Daryl J and Weirauch, Matthew T and Gilbert, James and Drenkow, Jorg and Bell, Ian and Zhao, XiaoDong and Srinivasan, K G and Sung, Wing-Kin and Ooi, Hong Sain and Chiu, Kuo Ping and Foissac, Sylvain and Alioto, Tyler and Brent, Michael and Pachter, Lior and Tress, Michael L and Valencia, Alfonso and Choo, Siew Woh and Choo, Chiou Yu and Ucla, Catherine and Manzano, Caroline and Wyss, Carine and Cheung, Evelyn and Clark, Taane G and Brown, James B and Ganesh, Madhavan and Patel, Sandeep and Tammana, Hari and Chrast, Jacqueline and Henrichsen, Charlotte N and Kai, Chikatoshi and Kawai, Jun and Nagalakshmi, Ugrappa and Wu, Jiaqian and Lian, Zheng and Lian, Jin and Newburger, Peter and Zhang, Xueqing and Bickel, Peter and Mattick, John S and Carninci, Piero and Hayashizaki, Yoshihide and Weissman, Sherman and Hubbard, Tim and Myers, Richard M and Rogers, Jane and Stadler, Peter F and Lowe, Todd M and Wei, Chia-Lin and Ruan, Yijun and Struhl, Kevin and Gerstein, Mark and Antonarakis, Stylianos E and Fu, Yutao and Green, Eric D and Kara\"{o}z, Ulaş and Siepel, Adam and Taylor, James and Liefer, Laura A and Wetterstrand, Kris A and Good, Peter J and Feingold, Elise A and Guyer, Mark S and Cooper, Gregory M and Asimenos, George and Dewey, Colin N and Hou, Minmei and Nikolaev, Sergey and Montoya-Burgos, Juan I and L\"{o}ytynoja, Ari and Whelan, Simon and Pardi, Fabio and Massingham, Tim and Huang, Haiyan and Zhang, Nancy R and Holmes, Ian and Mullikin, James C and Ureta-Vidal, Abel and Paten, Benedict and Seringhaus, Michael and Church, Deanna and Rosenbloom, Kate and Kent, W James and Stone, Eric A and {NISC Comparative Sequencing Program} and {Baylor College of Medicine Human Genome Sequencing Center} and {Washington University Genome Sequencing Center} and {Broad Institute} and {Children's Hospital Oakland Research Institute} and Batzoglou, Serafim and Goldman, Nick and Hardison, Ross C and Haussler, David and Miller, Webb and Sidow, Arend and Trinklein, Nathan D and Zhang, Zhengdong D and Barrera, Leah and Stuart, Rhona and King, David C and Ameur, Adam and Enroth, Stefan and Bieda, Mark C and Kim, Jonghwan and Bhinge, Akshay A and Jiang, Nan and Liu, Jun and Yao, Fei and Vega, Vinsensius B and Lee, Charlie W H and Ng, Patrick and Shahab, Atif and Yang, Annie and Moqtaderi, Zarmik and Zhu, Zhou and Xu, Xiaoqin and Squazzo, Sharon and Oberley, Matthew J and Inman, David and Singer, Michael A and Richmond, Todd A and Munn, Kyle J and Rada-Iglesias, Alvaro and Wallerman, Ola and Komorowski, Jan and Fowler, Joanna C and Couttet, Phillippe and Bruce, Alexander W and Dovey, Oliver M and Ellis, Peter D and Langford, Cordelia F and Nix, David A and Euskirchen, Ghia and Hartman, Stephen and Urban, Alexander E and Kraus, Peter and Van Calcar, Sara and Heintzman, Nate and Kim, Tae Hoon and Wang, Kun and Qu, Chunxu and Hon, Gary and Luna, Rosa and Glass, Christopher K and Rosenfeld, M Geoff and Aldred, Shelley Force and Cooper, Sara J and Halees, Anason and Lin, Jane M and Shulha, Hennady P and Zhang, Xiaoling and Xu, Mousheng and Haidar, Jaafar N S and Yu, Yong and Ruan, Yijun and Iyer, Vishwanath R and Green, Roland D and Wadelius, Claes and Farnham, Peggy J and Ren, Bing and Harte, Rachel A and Hinrichs, Angie S and Trumbower, Heather and Clawson, Hiram and Hillman-Jackson, Jennifer and Zweig, Ann S and Smith, Kayla and Thakkapallayil, Archana and Barber, Galt and Kuhn, Robert M and Karolchik, Donna and Armengol, Lluis and Bird, Christine P and de Bakker, Paul I W and Kern, Andrew D and Lopez-Bigas, Nuria and Martin, Joel D and Stranger, Barbara E and Woodroffe, Abigail and Davydov, Eugene and Dimas, Antigone and Eyras, Eduardo and Hallgr\'{\i}msd\'{o}ttir, Ingileif B and Huppert, Julian and Zody, Michael C and Abecasis, Gonçalo R and Estivill, Xavier and Bouffard, Gerard G and Guan, Xiaobin and Hansen, Nancy F and Idol, Jacquelyn R and Maduro, Valerie V B and Maskeri, Baishali and McDowell, Jennifer C and Park, Morgan and Thomas, Pamela J and Young, Alice C and Blakesley, Robert W and Muzny, Donna M and Sodergren, Erica and Wheeler, David A and Worley, Kim C and Jiang, Huaiyang and Weinstock, George M and Gibbs, Richard A and Graves, Tina and Fulton, Robert and Mardis, Elaine R and Wilson, Richard K and Clamp, Michele and Cuff, James and Gnerre, Sante and Jaffe, David B and Chang, Jean L and Lindblad-Toh, Kerstin and Lander, Eric S and Koriabine, Maxim and Nefedov, Mikhail and Osoegawa, Kazutoyo and Yoshinaga, Yuko and Zhu, Baoli and de Jong, Pieter J},
    title = {Identification and analysis of functional elements in 1\% of the human genome by the {ENCODE} pilot project},
    journal = {Nature},
    year = {2007},
    volume = {447},
    pages = {799--816},
    abstract = {We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.},
    doi = {10.1038/nature05874},
    issue = {7146},
    keywords = {Chromatin, genetics, metabolism; Chromatin Immunoprecipitation; Conserved Sequence, genetics; DNA Replication; Evolution, Molecular; Exons, genetics; Genetic Variation, genetics; Genome, Human, genetics; Genomics; Heterozygote; Histones, metabolism; Humans; Pilot Projects; Protein Binding; RNA, Messenger, genetics; RNA, Untranslated, genetics; Regulatory Sequences, Nucleic Acid, genetics; Transcription Factors, metabolism; Transcription Initiation Site; Transcription, Genetic, genetics},
    pmid = {17571346},
    }

2006

  • [DOI] J. Hertel, M. Lindemeyer, K. Missal, C. Fried, A. Tanzer, C. Flamm, I. L. Hofacker, P. F. Stadler, {. B. C. L. of 2004, and 2005}, "The expansion of the metazoan microRNA repertoire," BMC Genomics, vol. 7, p. 25, 2006.
    [Bibtex]
    @Article{Hertel:06,
    author = {Hertel, Jana and Lindemeyer, Manuela and Missal, Kristin and Fried, Claudia and Tanzer, Andrea and Flamm, Christoph and Hofacker, Ivo L and Stadler, Peter F and {Students of Bioinformatics Computer Labs 2004 and 2005}},
    title = {The expansion of the metazoan micro{RNA} repertoire},
    journal = {{BMC Genomics}},
    year = {2006},
    volume = {7},
    pages = {25},
    abstract = {MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript. We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters. Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.},
    doi = {10.1186/1471-2164-7-25},
    keywords = {Animals; Base Sequence; Cluster Analysis; DNA, chemistry; Evolution, Molecular; Gene Duplication; Humans; Mammals, genetics; MicroRNAs, chemistry, classification, genetics; Molecular Sequence Data; Multigene Family; Phylogeny; Repetitive Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid; Tubulin, genetics; Vertebrates, genetics},
    pmid = {16480513},
    }