title: Challenges in RNA virus bioinformatics.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Manja
authors.initials: M
authors.lastname: Marz
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USAFriedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz 
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Fricke
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USAFriedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz 
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Hofacker
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoffmann
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Middendorf
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rattei
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USAFriedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz 
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Friedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany, Moscow Institute of Physics and Technology, Institutskii Per. 9, Moscow Region, Dolgoprudny 141700, Russia, Institut für theoretische Chemie, Universität Wien, Währingerstraße 17, A-1090 Wien, Austria, Institute of Virology, Technical University of Munich, Trogerstr. 30, 81675 München, Germany, University of Leipzig, Faculty of Mathematics and Computer Science, Institute for Computer Science, Augustusplatz 10, 04109 Leipzig, Germany, Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, Universität Wien, Althanstraße 14, 1090 Wien, Austria, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany and The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USAFriedrich-Schiller-University Jena, Faculty of Mathematics und Computer Science, Leutragraben 1, 07743 Jena, Germany, Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland, Universitätsklinikum Bonn, Institut für Virologie, Sigmund-Freud-Str. 25, 53127 Bonn, Technische Universität Muenchen, Wissenschaftszentrum Weihenstephan, Am Forum 1, 85354 Freising, Helmholtz 
authors.forename: Armin
authors.initials: A
authors.lastname: Töpfer
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010802:Phylogeny; D012328:RNA Viruses / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics
chemical_list: D012367:RNA, Viral