TY - JOUR A1 - Whisnant, Adam W. A1 - Jürges, Christopher S. A1 - Hennig, Thomas A1 - Wyler, Emanuel A1 - Prusty, Bhupesh A1 - Rutkowski, Andrzej J. A1 - L'hernault, Anne A1 - Djakovic, Lara A1 - Göbel, Margarete A1 - Döring, Kristina A1 - Menegatti, Jennifer A1 - Antrobus, Robin A1 - Matheson, Nicholas J. A1 - Künzig, Florian W. H. A1 - Mastrobuoni, Guido A1 - Bielow, Chris A1 - Kempa, Stefan A1 - Liang, Chunguang A1 - Dandekar, Thomas A1 - Zimmer, Ralf A1 - Landthaler, Markus A1 - Grässer, Friedrich A1 - Lehner, Paul J. A1 - Friedel, Caroline C. A1 - Erhard, Florian A1 - Dölken, Lars T1 - Integrative functional genomics decodes herpes simplex virus 1 JF - Nature Communications N2 - The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research. KW - infected-cell protein KW - messenger RNA KW - binding protein KW - type 1 KW - identification KW - ICP27 KW - translation KW - expression KW - sequence KW - domain Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229884 VL - 11 ER - TY - JOUR A1 - Marenholz, Ingo A1 - Esparza-Gordillo, Jorge A1 - Rüschendorf, Franz A1 - Bauerfeind, Anja A1 - Strachan, David P. A1 - Spycher, Ben D. A1 - Baurecht, Hansjörg A1 - Magaritte-Jeannin, Patricia A1 - Sääf, Annika A1 - Kerkhof, Marjan A1 - Ege, Markus A1 - Baltic, Svetlana A1 - Matheson, Melanie C. A1 - Li, Jin A1 - Michel, Sven A1 - Ang, Wei Q. A1 - McArdle, Wendy A1 - Arnold, Andreas A1 - Homuth, Georg A1 - Demenais, Florence A1 - Bouzigon, Emmanuelle A1 - Söderhäll, Cilla A1 - Pershagen, Göran A1 - de Jongste, Johan C. A1 - Postma, Dirkje S. A1 - Braun-Fahrländer, Charlotte A1 - Horak, Elisabeth A1 - Ogorodova, Ludmila M. A1 - Puzyrev, Valery P. A1 - Bragina, Elena Yu A1 - Hudson, Thomas J. A1 - Morin, Charles A1 - Duffy, David L. A1 - Marks, Guy B. A1 - Robertson, Colin F. A1 - Montgomery, Grant W. A1 - Musk, Bill A1 - Thompson, Philip J. A1 - Martin, Nicholas G. A1 - James, Alan A1 - Sleiman, Patrick A1 - Toskala, Elina A1 - Rodriguez, Elke A1 - Fölster-Holst, Regina A1 - Franke, Andre A1 - Lieb, Wolfgang A1 - Gieger, Christian A1 - Heinzmann, Andrea A1 - Rietschel, Ernst A1 - Keil, Thomas A1 - Cichon, Sven A1 - Nöthen, Markus M. A1 - Pennel, Craig E. A1 - Sly, Peter D. A1 - Schmidt, Carsten O. A1 - Matanovic, Anja A1 - Schneider, Valentin A1 - Heinig, Matthias A1 - Hübner, Norbert A1 - Holt, Patrick G. A1 - Lau, Susanne A1 - Kabesch, Michael A1 - Weidinger, Stefan A1 - Hakonarson, Hakon A1 - Ferreira, Manuel A. R. A1 - Laprise, Catherine A1 - Freidin, Maxim B. A1 - Genuneit, Jon A1 - Koppelman, Gerard H. A1 - Melén, Erik A1 - Dizier, Marie-Hélène A1 - Henderson, A. John A1 - Lee, Young Ae T1 - Meta-analysis identifies seven susceptibility loci involved in the atopic march JF - Nature Communications N2 - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema. KW - chromosome 11Q13 KW - risk KW - genomewide association KW - hay fever KW - birth cohort KW - filaggrin mutations KW - food allergy KW - juvenile myoclonic epilepsy KW - childhood asthma KW - dermatitis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835 VL - 6 IS - 8804 ER -