“The double helix is indeed a remarkable molecule. Modern man is perhaps 50,000 years old, civilization has existed for scarcely 10,000 years and the United States for only just over 200 years; but DNA and RNA have been around for at least several billion years. All that time the double helix has been there, and active, and yet we are the first creatures on Earth to become aware of its existence.”
Francis Crick (1916–2004)
E-Mail: kevin.lamkiewicz@uni-jena.de
Room: 08S06
Phone: +49-3641-9-46484
CV: Click here
Publications
2022
Sofer, Summer; Lamkiewicz, Kevin; Eilat, Shir Armoza; Partouche, Shirly; Marz, Manja; Moskovits, Neta; Stemmer, Salomon M; Shlomai, Amir; Sklan, Ella H
In: FASEB J , vol. 36, iss. 3, pp. e22191, 2022.
@article{Sofer2022,
title = {A genome-wide CRISPR activation screen reveals Hexokinase 1 as a critical factor in promoting resistance to multi-kinase inhibitors in hepatocellular carcinoma cells},
author = {Summer Sofer and Kevin Lamkiewicz and Shir Armoza Eilat and Shirly Partouche and Manja Marz and Neta Moskovits and Salomon M Stemmer and Amir Shlomai and Ella H Sklan},
doi = {10.1096/fj.202101507RR},
year = {2022},
date = {2022-02-11},
urldate = {2022-02-11},
journal = {FASEB J },
volume = {36},
issue = {3},
pages = {e22191},
abstract = {Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage and is, therefore, treated with systemic drugs, such as tyrosine-kinase inhibitors (TKIs). These drugs, however, offer only modest survival benefits due to the rapid development of drug resistance. To identify genes implicated in TKI resistance, a cluster of regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 activation screen was performed in hepatoma cells treated with regorafenib, a TKI used as second-line therapy for advanced HCC. The screen results show that Hexokinase 1 (HK1), catalyzing the first step in glucose metabolism, is a top candidate for conferring TKI resistance. Compatible with this, HK1 was upregulated in regorafenib-resistant cells. Using several experimental approaches, both in vitro and in vivo, we show that TKI resistance correlates with HK1 expression. Furthermore, an HK inhibitor resensitized resistant cells to TKI treatment. Together, our data indicate that HK1 may function as a critical factor modulating TKI resistance in hepatoma cells and, therefore, may serve as a biomarker for treatment success.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage and is, therefore, treated with systemic drugs, such as tyrosine-kinase inhibitors (TKIs). These drugs, however, offer only modest survival benefits due to the rapid development of drug resistance. To identify genes implicated in TKI resistance, a cluster of regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 activation screen was performed in hepatoma cells treated with regorafenib, a TKI used as second-line therapy for advanced HCC. The screen results show that Hexokinase 1 (HK1), catalyzing the first step in glucose metabolism, is a top candidate for conferring TKI resistance. Compatible with this, HK1 was upregulated in regorafenib-resistant cells. Using several experimental approaches, both in vitro and in vivo, we show that TKI resistance correlates with HK1 expression. Furthermore, an HK inhibitor resensitized resistant cells to TKI treatment. Together, our data indicate that HK1 may function as a critical factor modulating TKI resistance in hepatoma cells and, therefore, may serve as a biomarker for treatment success.
Fuchs, Jonas; Lamkiewicz, Kevin; Kolesnikova, Larissa; Hölzer, Martin; Marz, Manja; Kochs, Georg
Comparative study of ten thogotovirus isolates and their distinct in vivo characteristics Journal Article
In: J Virol, 2022.
@article{nokey,
title = {Comparative study of ten thogotovirus isolates and their distinct in vivo characteristics},
author = {Jonas Fuchs and Kevin Lamkiewicz and Larissa Kolesnikova and Martin Hölzer and Manja Marz and Georg Kochs},
doi = {10.1128/JVI.01556-21},
year = {2022},
date = {2022-01-12},
journal = {J Virol},
abstract = {Thogotoviruses are tick-borne arboviruses that comprise a unique genus within the Orthomyxoviridae family. Infections with thogotoviruses primarily cause disease in livestock with occasional reports of human infections suggesting a zoonotic potential. In the past, multiple genetically distinct thogotoviruses were isolated mostly from collected ticks. However, many aspects regarding their phylogenetic relationships, morphological characteristics and virulence in mammals remain unclear. For the present comparative study, we used a collection of ten different thogotovirus isolates from different geographic areas. Next generation sequencing and subsequent phylogenetic analyses revealed a distinct separation of these viruses into two major clades - the Thogoto-like and Dhori-like viruses. Electron microscopy demonstrated a heterogeneous morphology with spherical and filamentous particles being present in virus preparations. To study their pathogenicity, we analyzed the viruses in a small animal model system. In intraperitoneally infected C57BL/6 mice, all isolates showed a tropism for liver, lung and spleen. Importantly, we did not observe horizontal transmission to uninfected, highly susceptible contact mice. The isolates enormously differed in their capacity to induce disease, ranging from subclinical to fatal outcomes. In vivo multi-step passaging experiments of two low-pathogenic isolates showed no increased virulence and sequence analyses of the passaged viruses indicated a high stability of the viral genomes after ten mouse passages. In summary, our analysis demonstrates the broad genetic and phenotypic variability within the thogotovirus genus. Moreover, thogotoviruses are well adapted to mammals but their horizontal transmission seems to depend on ticks as their vectors. Importance Since their discovery over sixty years ago, fifteen genetically distinct members of the thogotovirus genus have been isolated. These arboviruses belong to the Orthomyxovirus family and share many features with influenza viruses. However, numerous of these isolates have not been characterized in depth. In the present study, we comparatively analyzed a collection of ten different thogotovirus isolates to answer basic questions about their phylogenetic relationships, morphology and pathogenicity in mice. Our results highlight shared and unique characteristics of this diverse genus. Taken together, these observations provide a framework for the phylogenic classification and phenotypic characterization of newly identified thogotovirus isolates that could potentially cause severe human infections as exemplified by the recently reported, fatal Bourbon virus cases in the United States.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Thogotoviruses are tick-borne arboviruses that comprise a unique genus within the Orthomyxoviridae family. Infections with thogotoviruses primarily cause disease in livestock with occasional reports of human infections suggesting a zoonotic potential. In the past, multiple genetically distinct thogotoviruses were isolated mostly from collected ticks. However, many aspects regarding their phylogenetic relationships, morphological characteristics and virulence in mammals remain unclear. For the present comparative study, we used a collection of ten different thogotovirus isolates from different geographic areas. Next generation sequencing and subsequent phylogenetic analyses revealed a distinct separation of these viruses into two major clades - the Thogoto-like and Dhori-like viruses. Electron microscopy demonstrated a heterogeneous morphology with spherical and filamentous particles being present in virus preparations. To study their pathogenicity, we analyzed the viruses in a small animal model system. In intraperitoneally infected C57BL/6 mice, all isolates showed a tropism for liver, lung and spleen. Importantly, we did not observe horizontal transmission to uninfected, highly susceptible contact mice. The isolates enormously differed in their capacity to induce disease, ranging from subclinical to fatal outcomes. In vivo multi-step passaging experiments of two low-pathogenic isolates showed no increased virulence and sequence analyses of the passaged viruses indicated a high stability of the viral genomes after ten mouse passages. In summary, our analysis demonstrates the broad genetic and phenotypic variability within the thogotovirus genus. Moreover, thogotoviruses are well adapted to mammals but their horizontal transmission seems to depend on ticks as their vectors. Importance Since their discovery over sixty years ago, fifteen genetically distinct members of the thogotovirus genus have been isolated. These arboviruses belong to the Orthomyxovirus family and share many features with influenza viruses. However, numerous of these isolates have not been characterized in depth. In the present study, we comparatively analyzed a collection of ten different thogotovirus isolates to answer basic questions about their phylogenetic relationships, morphology and pathogenicity in mice. Our results highlight shared and unique characteristics of this diverse genus. Taken together, these observations provide a framework for the phylogenic classification and phenotypic characterization of newly identified thogotovirus isolates that could potentially cause severe human infections as exemplified by the recently reported, fatal Bourbon virus cases in the United States.
2021
Pappas, Nikolaos; Roux, Simon; Hölzer, Martin; Lamkiewicz, Kevin; Mock, Florian; Marz, Manja; Dutilh, Bas E.
Virus Bioinformatics Incollection
In: Reference Module in Life Sciences, vol. 1, pp. 124-132, Elsevier, 2021, ISBN: 978-0-12-809633-8.
@incollection{Pappas:20,
title = {Virus Bioinformatics},
author = {Nikolaos Pappas and Simon Roux and Martin Hölzer and Kevin Lamkiewicz and Florian Mock and Manja Marz and Bas E. Dutilh},
doi = {10.1016/B978-0-12-814515-9.00034-5},
isbn = {978-0-12-809633-8},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
booktitle = {Reference Module in Life Sciences},
volume = {1},
pages = {124-132},
publisher = {Elsevier},
abstract = {Since the discovery of computers, bioinformatics and computational biology have been instrumental in a wide range of discoveries in virology. These include early mathematical models of virus-host interaction, and more recently the analysis of viral nucleotide and protein sequences to track their function, epidemiology, and evolution. The genomics revolution has provided an unprecedented amount of sequence information from both viruses and their hosts. In this article, we discuss how bioinformatics allows viral sequence data to be analyzed and interpreted, including an overview of commonly used tools and examples of applications.
},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Since the discovery of computers, bioinformatics and computational biology have been instrumental in a wide range of discoveries in virology. These include early mathematical models of virus-host interaction, and more recently the analysis of viral nucleotide and protein sequences to track their function, epidemiology, and evolution. The genomics revolution has provided an unprecedented amount of sequence information from both viruses and their hosts. In this article, we discuss how bioinformatics allows viral sequence data to be analyzed and interpreted, including an overview of commonly used tools and examples of applications.
2020
Hufsky, Franziska; Beerenwinkel, Niko; Meyer, Irmtraud M.; Roux, Simon; Cook, Georgia May; Kinsella, Cormac M.; Lamkiewicz, Kevin; Marquet, Mike; Nieuwenhuijse, David F.; Olendraite, Ingrida; Paraskevopoulou, Sofia; Young, Francesca; Dijkman, Ronald; Ibrahim, Bashar; Kelly, Jenna; Mercier, Philippe Le; Marz, Manja; Ramette, Alban; Thiel, Volker
The International Virus Bioinformatics Meeting 2020 Journal Article
In: Viruses, vol. 12, no. 12, pp. 1398, 2020.
@article{Hufsky:20b,
title = {The International Virus Bioinformatics Meeting 2020},
author = {Franziska Hufsky and Niko Beerenwinkel and Irmtraud M. Meyer and Simon Roux and Georgia May Cook and Cormac M. Kinsella and Kevin Lamkiewicz and Mike Marquet and David F. Nieuwenhuijse and Ingrida Olendraite and Sofia Paraskevopoulou and Francesca Young and Ronald Dijkman and Bashar Ibrahim and Jenna Kelly and Philippe Le Mercier and Manja Marz and Alban Ramette and Volker Thiel},
doi = {10.3390/v12121398},
year = {2020},
date = {2020-12-06},
urldate = {2020-01-01},
journal = {Viruses},
volume = {12},
number = {12},
pages = {1398},
publisher = {MDPI AG},
abstract = {The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, in March 2020. However, the COVID-19 pandemic put a spoke in the wheel of almost all conferences to be held in 2020. After moving the conference to 8–9 October 2020, we got hit by the second wave and finally decided at short notice to go fully online. On the other hand, the pandemic has made us even more aware of the importance of accelerating research in viral bioinformatics. Advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks. The International Virus Bioinformatics Meeting 2020 has attracted approximately 120 experts in virology and bioinformatics from all over the world to join the two-day virtual meeting. Despite concerns being raised that virtual meetings lack possibilities for face-to-face discussion, the participants from this small community created a highly interactive scientific environment, engaging in lively and inspiring discussions and suggesting new research directions and questions. The meeting featured five invited and twelve contributed talks, on the four main topics: (1) proteome and RNAome of RNA viruses, (2) viral metagenomics and ecology, (3) virus evolution and classification and (4) viral infections and immunology. Further, the meeting featured 20 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, in March 2020. However, the COVID-19 pandemic put a spoke in the wheel of almost all conferences to be held in 2020. After moving the conference to 8–9 October 2020, we got hit by the second wave and finally decided at short notice to go fully online. On the other hand, the pandemic has made us even more aware of the importance of accelerating research in viral bioinformatics. Advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks. The International Virus Bioinformatics Meeting 2020 has attracted approximately 120 experts in virology and bioinformatics from all over the world to join the two-day virtual meeting. Despite concerns being raised that virtual meetings lack possibilities for face-to-face discussion, the participants from this small community created a highly interactive scientific environment, engaging in lively and inspiring discussions and suggesting new research directions and questions. The meeting featured five invited and twelve contributed talks, on the four main topics: (1) proteome and RNAome of RNA viruses, (2) viral metagenomics and ecology, (3) virus evolution and classification and (4) viral infections and immunology. Further, the meeting featured 20 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.
Kalvari, Ioanna; Nawrocki, Eric P; Ontiveros-Palacios, Nancy; Argasinska, Joanna; Lamkiewicz, Kevin; Marz, Manja; Griffiths-Jones, Sam; Toffano-Nioche, Claire; Gautheret, Daniel; Weinberg, Zasha; Rivas, Elena; Eddy, Sean R; Finn, Robert D; Bateman, Alex; Petrov, Anton I
Rfam 14: expanded coverage of metagenomic, viral and microRNA families Journal Article
In: Nucleic Acids Res, vol. 49, no. D1, pp. D192–D200, 2020.
@article{Kalvari:21,
title = {Rfam 14: expanded coverage of metagenomic, viral and microRNA families},
author = {Ioanna Kalvari and Eric P Nawrocki and Nancy Ontiveros-Palacios and Joanna Argasinska and Kevin Lamkiewicz and Manja Marz and Sam Griffiths-Jones and Claire Toffano-Nioche and Daniel Gautheret and Zasha Weinberg and Elena Rivas and Sean R Eddy and Robert D Finn and Alex Bateman and Anton I Petrov},
url = {https://rfam.org/},
doi = {10.1093/nar/gkaa1047},
year = {2020},
date = {2020-11-19},
urldate = {2020-11-19},
journal = {Nucleic Acids Res},
volume = {49},
number = {D1},
pages = {D192--D200},
publisher = {Oxford University Press (OUP)},
abstract = {Rfam is a database of RNA families where each of the 3444 families is represented by a multiple sequence alignment of known RNA sequences and a covariance model that can be used to search for additional members of the family. Recent developments have involved expert collaborations to improve the quality and coverage of Rfam data, focusing on microRNAs, viral and bacterial RNAs. We have completed the first phase of synchronising microRNA families in Rfam and miRBase, creating 356 new Rfam families and updating 40. We established a procedure for comprehensive annotation of viral RNA families starting with Flavivirus and Coronaviridae RNAs. We have also increased the coverage of bacterial and metagenome-based RNA families from the ZWD database. These developments have enabled a significant growth of the database, with the addition of 759 new families in Rfam 14. To facilitate further community contribution to Rfam, expert users are now able to build and submit new families using the newly developed Rfam Cloud family curation system. New Rfam website features include a new sequence similarity search powered by RNAcentral, as well as search and visualisation of families with pseudoknots. Rfam is freely available at https://rfam.org.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rfam is a database of RNA families where each of the 3444 families is represented by a multiple sequence alignment of known RNA sequences and a covariance model that can be used to search for additional members of the family. Recent developments have involved expert collaborations to improve the quality and coverage of Rfam data, focusing on microRNAs, viral and bacterial RNAs. We have completed the first phase of synchronising microRNA families in Rfam and miRBase, creating 356 new Rfam families and updating 40. We established a procedure for comprehensive annotation of viral RNA families starting with Flavivirus and Coronaviridae RNAs. We have also increased the coverage of bacterial and metagenome-based RNA families from the ZWD database. These developments have enabled a significant growth of the database, with the addition of 759 new families in Rfam 14. To facilitate further community contribution to Rfam, expert users are now able to build and submit new families using the newly developed Rfam Cloud family curation system. New Rfam website features include a new sequence similarity search powered by RNAcentral, as well as search and visualisation of families with pseudoknots. Rfam is freely available at https://rfam.org.
Hufsky, Franziska; Lamkiewicz, Kevin; Almeida, Alexandre; Aouacheria, Abdel; Arighi, Cecilia; Bateman, Alex; Baumbach, Jan; Beerenwinkel, Niko; Brandt, Christian; Cacciabue, Marco; Chuguransky, Sara; Drechsel, Oliver; Finn, Robert D; Fritz, Adrian; Fuchs, Stephan; Hattab, Georges; Hauschild, Anne-Christin; Heider, Dominik; Hoffmann, Marie; Hölzer, Martin; Hoops, Stefan; Kaderali, Lars; Kalvari, Ioanna; Kleist, Max; Kmiecinski, Renó; Kühnert, Denise; Lasso, Gorka; Libin, Pieter; List, Markus; Löchel, Hannah F; Martin, Maria J; Martin, Roman; Matschinske, Julian; McHardy, Alice C; Mendes, Pedro; Mistry, Jaina; Navratil, Vincent; Nawrocki, Eric P; O'Toole, Áine Niamh; Ontiveros-Palacios, Nancy; Petrov, Anton I; Rangel-Pineros, Guillermo; Redaschi, Nicole; Reimering, Susanne; Reinert, Knut; Reyes, Alejandro; Richardson, Lorna; Robertson, David L; Sadegh, Sepideh; Singer, Joshua B; Theys, Kristof; Upton, Chris; Welzel, Marius; Williams, Lowri; Marz, Manja
Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research Journal Article
In: Brief Bioinform, vol. 22, no. 2, pp. 642–663, 2020.
@article{Hufsky:20a,
title = {Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research},
author = {Franziska Hufsky and Kevin Lamkiewicz and Alexandre Almeida and Abdel Aouacheria and Cecilia Arighi and Alex Bateman and Jan Baumbach and Niko Beerenwinkel and Christian Brandt and Marco Cacciabue and Sara Chuguransky and Oliver Drechsel and Robert D Finn and Adrian Fritz and Stephan Fuchs and Georges Hattab and Anne-Christin Hauschild and Dominik Heider and Marie Hoffmann and Martin Hölzer and Stefan Hoops and Lars Kaderali and Ioanna Kalvari and Max Kleist and Renó Kmiecinski and Denise Kühnert and Gorka Lasso and Pieter Libin and Markus List and Hannah F Löchel and Maria J Martin and Roman Martin and Julian Matschinske and Alice C McHardy and Pedro Mendes and Jaina Mistry and Vincent Navratil and Eric P Nawrocki and Áine Niamh O'Toole and Nancy Ontiveros-Palacios and Anton I Petrov and Guillermo Rangel-Pineros and Nicole Redaschi and Susanne Reimering and Knut Reinert and Alejandro Reyes and Lorna Richardson and David L Robertson and Sepideh Sadegh and Joshua B Singer and Kristof Theys and Chris Upton and Marius Welzel and Lowri Williams and Manja Marz},
url = {http://evbc.uni-jena.de/tools/coronavirus-tools/},
doi = {10.1093/bib/bbaa232},
year = {2020},
date = {2020-11-04},
urldate = {2020-11-04},
journal = {Brief Bioinform},
volume = {22},
number = {2},
pages = {642--663},
publisher = {Oxford University Press (OUP)},
abstract = {SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories.
Jordan-Paiz, Ana; Nevot, Maria; Lamkiewicz, Kevin; Lataretu, Marie; Franco, Sandra; Marz, Manja; Martinez, Miguel Angel
HIV-1 lethality and loss of Env protein expression induced by single synonymous substitutions in the virus genome intronic splicing silencer Journal Article
In: J Virol, vol. 94, no. 21, 2020.
@article{Jordan-Paiz:20,
title = {HIV-1 lethality and loss of Env protein expression induced by single synonymous substitutions in the virus genome intronic splicing silencer},
author = {Ana Jordan-Paiz and Maria Nevot and Kevin Lamkiewicz and Marie Lataretu and Sandra Franco and Manja Marz and Miguel Angel Martinez},
doi = {10.1128/jvi.01108-20},
year = {2020},
date = {2020-10-14},
urldate = {2020-01-01},
journal = {J Virol},
volume = {94},
number = {21},
publisher = {American Society for Microbiology},
abstract = {Synonymous genome recoding has been widely used to study different aspects of virus biology. Codon usage affects the temporal regulation of viral gene expression. In this study, we performed synonymous codon mutagenesis to investigate whether codon usage affected HIV-1 Env protein expression and virus viability. We replaced the codons AGG, GAG, CCU, ACU, CUC, and GGG of the HIV-1 env gene with the synonymous codons CGU, GAA, CCG, ACG, UUA, and GGA, respectively. We found that recoding the Env protein gp120 coding region (excluding the Rev response element [RRE]) did not significantly affect virus replication capacity, even though we introduced 15 new CpG dinucleotides. In contrast, changing a single codon (AGG to CGU) located in the gp41 coding region (HXB2 env position 2125 to 2127), which was included in the intronic splicing silencer (ISS), completely abolished virus replication and Env expression. Computational analyses of this mutant revealed a severe disruption in the ISS RNA secondary structure. A variant that restored ISS secondary RNA structure also reestablished Env production and virus viability. Interestingly, this codon variant prevented both virus replication and Env translation in a eukaryotic expression system. These findings suggested that disrupting mRNA splicing was not the only means of inhibiting translation. Our findings indicated that synonymous gp120 recoding was not always deleterious to HIV-1 replication. Importantly¸ we found that disrupting an external ISS loop strongly affected HIV-1 replication and Env translation.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Synonymous genome recoding has been widely used to study different aspects of virus biology. Codon usage affects the temporal regulation of viral gene expression. In this study, we performed synonymous codon mutagenesis to investigate whether codon usage affected HIV-1 Env protein expression and virus viability. We replaced the codons AGG, GAG, CCU, ACU, CUC, and GGG of the HIV-1 env gene with the synonymous codons CGU, GAA, CCG, ACG, UUA, and GGA, respectively. We found that recoding the Env protein gp120 coding region (excluding the Rev response element [RRE]) did not significantly affect virus replication capacity, even though we introduced 15 new CpG dinucleotides. In contrast, changing a single codon (AGG to CGU) located in the gp41 coding region (HXB2 env position 2125 to 2127), which was included in the intronic splicing silencer (ISS), completely abolished virus replication and Env expression. Computational analyses of this mutant revealed a severe disruption in the ISS RNA secondary structure. A variant that restored ISS secondary RNA structure also reestablished Env production and virus viability. Interestingly, this codon variant prevented both virus replication and Env translation in a eukaryotic expression system. These findings suggested that disrupting mRNA splicing was not the only means of inhibiting translation. Our findings indicated that synonymous gp120 recoding was not always deleterious to HIV-1 replication. Importantly¸ we found that disrupting an external ISS loop strongly affected HIV-1 replication and Env translation.
Hufsky, Franziska; Lamkiewicz, Kevin; Almeida, Alexandre; Aouacheria, Abdel; Arighi, Cecilia; Bateman, Alex; Baumbach, Jan; Beerenwinkel, Niko; Brandt, Christian; Cacciabue, Marco; Chuguransky, Sara; Drechsel, Oliver; Finn, Robert D.; Fritz, Adrian; Fuchs, Stephan; Hattab, Georges; Hauschild, Anne-Christin; Heider, Dominik; Hoffmann, Marie; Hölzer, Martin; Hoops, Stefan; Kaderali, Lars; Kalvari, Ioanna; Kleist, Max; Kmiecinski, Rene; Kühnert, Denise; Lasso, Gorka; Libin, Pieter; List, Markus; Löchel, Hannah F.; Martin, Maria J.; Martin, Roman; Matschinske, Julian; McHardy, Alice C.; Mendes, Pedro; Mistry, Jaina; Navratil, Vincent; Nawrocki, Eric; O'Toole, Áine Niamh; Palacios-Ontiveros, Nancy; Petrov, Anton I.; Rangel-Piñeros, Guillermo; Redaschi, Nicole; Reimering, Susanne; Reinert, Knut; Reyes, Alejandro; Richardson, Lorna; Robertson, David L.; Sadegh, Sepideh; Singer, Joshua B.; Theys, Kristof; Upton, Chris; Welzel, Marius; Williams, Lowri; Marz, Manja
Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research Journal Article
In: Preprints, 2020, (Now published in Brief Bioinform: https://dx.doi.org/10.1093/bib/bbaa232).
@article{Hufsky:20,
title = {Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research},
author = {Franziska Hufsky and Kevin Lamkiewicz and Alexandre Almeida and Abdel Aouacheria and Cecilia Arighi and Alex Bateman and Jan Baumbach and Niko Beerenwinkel and Christian Brandt and Marco Cacciabue and Sara Chuguransky and Oliver Drechsel and Robert D. Finn and Adrian Fritz and Stephan Fuchs and Georges Hattab and Anne-Christin Hauschild and Dominik Heider and Marie Hoffmann and Martin Hölzer and Stefan Hoops and Lars Kaderali and Ioanna Kalvari and Max Kleist and Rene Kmiecinski and Denise Kühnert and Gorka Lasso and Pieter Libin and Markus List and Hannah F. Löchel and Maria J. Martin and Roman Martin and Julian Matschinske and Alice C. McHardy and Pedro Mendes and Jaina Mistry and Vincent Navratil and Eric Nawrocki and Áine Niamh O'Toole and Nancy Palacios-Ontiveros and Anton I. Petrov and Guillermo Rangel-Piñeros and Nicole Redaschi and Susanne Reimering and Knut Reinert and Alejandro Reyes and Lorna Richardson and David L. Robertson and Sepideh Sadegh and Joshua B. Singer and Kristof Theys and Chris Upton and Marius Welzel and Lowri Williams and Manja Marz},
doi = {10.20944/preprints202005.0376.v1},
year = {2020},
date = {2020-05-23},
urldate = {2020-05-23},
journal = {Preprints},
publisher = {MDPI AG},
abstract = {SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding, and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are freely available online, either through web applications or public code repositories.
},
note = {Now published in Brief Bioinform: https://dx.doi.org/10.1093/bib/bbaa232},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding, and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are freely available online, either through web applications or public code repositories.
Hölzer, Martin; Barf, Lisa-Marie; Lamkiewicz, Kevin; Vorimore, Fabien; Lataretu, Marie; Favaroni, Alison; Schnee, Christiane; Laroucau, Karine; Marz, Manja; Sachse, Konrad
Comparative Genome Analysis of 33 Chlamydia Strains Reveals Characteristic Features of Chlamydia Psittaci and Closely Related Species Journal Article
In: Pathogens, vol. 9, no. 11, pp. 899, 2020.
@article{Hölzer:20,
title = {Comparative Genome Analysis of 33 \textit{Chlamydia} Strains Reveals Characteristic Features of \textit{Chlamydia Psittaci} and Closely Related Species},
author = {Martin Hölzer and Lisa-Marie Barf and Kevin Lamkiewicz and Fabien Vorimore and Marie Lataretu and Alison Favaroni and Christiane Schnee and Karine Laroucau and Manja Marz and Konrad Sachse},
url = {github.com/hoelzer-lab/ribap},
doi = {10.3390/pathogens9110899},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Pathogens},
volume = {9},
number = {11},
pages = {899},
publisher = {MDPI AG},
abstract = {To identify genome-based features characteristic of the avian and human pathogen Chlamydia (C.) psittaci and related chlamydiae, we analyzed whole-genome sequences of 33 strains belonging to 12 species. Using a novel genome analysis tool termed Roary ILP Bacterial Annotation Pipeline (RIBAP), this panel of strains was shown to share a large core genome comprising 784 genes and representing approximately 80% of individual genomes. Analyzing the most variable genomic sites, we identified a set of features of C. psittaci that in its entirety is characteristic of this species: (i) a relatively short plasticity zone of less than 30,000 nt without a tryptophan operon (also in C. abortus, C. avium, C. gallinacea, C. pneumoniae), (ii) a characteristic set of of Inc proteins comprising IncA, B, C, V, X, Y (with homologs in C. abortus, C. caviae and C. felis as closest relatives), (iii) a 502-aa SinC protein, the largest among Chlamydia spp., and (iv) an elevated number of Pmp proteins of subtype G (14 in C. psittaci, 14 in Cand. C. ibidis). In combination with future functional studies, the common and distinctive criteria revealed in this study provide important clues for understanding the complexity of host-specific behavior of individual Chlamydia spp.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To identify genome-based features characteristic of the avian and human pathogen Chlamydia (C.) psittaci and related chlamydiae, we analyzed whole-genome sequences of 33 strains belonging to 12 species. Using a novel genome analysis tool termed Roary ILP Bacterial Annotation Pipeline (RIBAP), this panel of strains was shown to share a large core genome comprising 784 genes and representing approximately 80% of individual genomes. Analyzing the most variable genomic sites, we identified a set of features of C. psittaci that in its entirety is characteristic of this species: (i) a relatively short plasticity zone of less than 30,000 nt without a tryptophan operon (also in C. abortus, C. avium, C. gallinacea, C. pneumoniae), (ii) a characteristic set of of Inc proteins comprising IncA, B, C, V, X, Y (with homologs in C. abortus, C. caviae and C. felis as closest relatives), (iii) a 502-aa SinC protein, the largest among Chlamydia spp., and (iv) an elevated number of Pmp proteins of subtype G (14 in C. psittaci, 14 in Cand. C. ibidis). In combination with future functional studies, the common and distinctive criteria revealed in this study provide important clues for understanding the complexity of host-specific behavior of individual Chlamydia spp.
2019
Mostajo, Nelly F.; Lataretu, Marie; Krautwurst, Sebastian; Mock, Florian; Desirò, Daniel; Lamkiewicz, Kevin; Collatz, Maximilian; Schoen, Andreas; Weber, Friedemann; Marz, Manja; Hölzer, Martin
A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes Journal Article
In: NAR Genomics Bioinf, vol. 2, no. 1, pp. lqz006, 2019.
@article{Mostajo:20,
title = {A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes},
author = {Nelly F. Mostajo and Marie Lataretu and Sebastian Krautwurst and Florian Mock and Daniel Desirò and Kevin Lamkiewicz and Maximilian Collatz and Andreas Schoen and Friedemann Weber and Manja Marz and Martin Hölzer},
url = {https://www.rna.uni-jena.de/supplements/bats/index.html},
doi = {10.1093/nargab/lqz006},
year = {2019},
date = {2019-09-30},
urldate = {2019-09-30},
journal = {NAR Genomics Bioinf},
volume = {2},
number = {1},
pages = {lqz006},
abstract = {Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.
Viehweger, Adrian; Krautwurst, Sebastian; Lamkiewicz, Kevin; Madhugiri, Ramakanth; Ziebuhr, John; Hölzer, Martin; Marz, Manja
In: Genome Res, vol. 29, pp. 1545-1554, 2019.
@article{Viehweger:19a,
title = {Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis.},
author = {Adrian Viehweger and Sebastian Krautwurst and Kevin Lamkiewicz and Ramakanth Madhugiri and John Ziebuhr and Martin Hölzer and Manja Marz},
doi = {10.1101/gr.247064.118},
year = {2019},
date = {2019-08-22},
urldate = {2019-08-22},
journal = {Genome Res},
volume = {29},
pages = {1545-1554},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called “quasispecies.” Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called “quasispecies.” Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.
Dukhovny, Anna; Lamkiewicz, Kevin; Chen, Qian; Fricke, Markus; Jabrane-Ferrat, Nabila; Marz, Manja; Jung, Jae U.; Sklan, Ella H.
A CRISPR activation screen identifies genes protecting from Zika virus infection Journal Article
In: J Virol, vol. 93, no. 16, 2019.
@article{Dukhovny:19,
title = {A CRISPR activation screen identifies genes protecting from Zika virus infection},
author = {Anna Dukhovny and Kevin Lamkiewicz and Qian Chen and Markus Fricke and Nabila Jabrane-Ferrat and Manja Marz and Jae U. Jung and Ella H. Sklan},
doi = {10.1128/JVI.00211-19},
year = {2019},
date = {2019-07-30},
urldate = {2019-07-30},
journal = {J Virol},
volume = {93},
number = {16},
publisher = {American Society for Microbiology Journals},
abstract = {Zika virus (ZIKV) is an arthropod borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré 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-Barré 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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Zika virus (ZIKV) is an arthropod borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré 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-Barré 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.
Peter, Stephan; Hölzer, Martin; Lamkiewicz, Kevin; Fenizio, Pietro Speroni; Hwaeer, Hassan Al; Marz, Manja; Schuster, Stefan; Dittrich, Peter; Ibrahim, Bashar
Structure and Hierarchy of Influenza Virus Models Revealed by Reaction Network Analysis Journal Article
In: Viruses, vol. 11, no. 5, pp. 449, 2019.
@article{Peter:19,
title = {Structure and Hierarchy of Influenza Virus Models Revealed by Reaction Network Analysis},
author = {Stephan Peter and Martin Hölzer and Kevin Lamkiewicz and Pietro Speroni Fenizio and Hassan Al Hwaeer and Manja Marz and Stefan Schuster and Peter Dittrich and Bashar Ibrahim},
doi = {10.3390/v11050449},
year = {2019},
date = {2019-05-16},
urldate = {2019-01-01},
journal = {Viruses},
volume = {11},
number = {5},
pages = {449},
publisher = {MDPI AG},
abstract = {Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in recent decades to capture viral dynamics within a host. These models differ in their complexity in terms of number of species elements and number of reactions. Here, we present a new approach to understanding the overall structure of twelve influenza A virus infection models and their relationship to each other. To this end, we apply chemical organization theory to obtain a hierarchical decomposition of the models into chemical organizations. The decomposition is based on the model structure (reaction rules) but is independent of kinetic details such as rate constants. We found different types of model structures ranging from two to eight organizations. Furthermore, the model’s organizations imply a partial order among models entailing a hierarchy of model, revealing a high model diversity with respect to their long-term behavior. Our methods and results can be helpful in model development and model integration, also beyond the influenza area. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in recent decades to capture viral dynamics within a host. These models differ in their complexity in terms of number of species elements and number of reactions. Here, we present a new approach to understanding the overall structure of twelve influenza A virus infection models and their relationship to each other. To this end, we apply chemical organization theory to obtain a hierarchical decomposition of the models into chemical organizations. The decomposition is based on the model structure (reaction rules) but is independent of kinetic details such as rate constants. We found different types of model structures ranging from two to eight organizations. Furthermore, the model’s organizations imply a partial order among models entailing a hierarchy of model, revealing a high model diversity with respect to their long-term behavior. Our methods and results can be helpful in model development and model integration, also beyond the influenza area.
Hufsky, Franziska; Ibrahim, Bashar; Modha, Sejal; Clokie, Martha R. J.; Deinhardt-Emmer, Stefanie; Dutilh, Bas E.; Lycett, Samantha; Simmonds, Peter; Thiel, Volker; Abroi, Aare; Adriaenssens, Evelien M.; Escalera-Zamudio, Marina; Kelly, Jenna Nicole; Lamkiewicz, Kevin; Lu, Lu; Susat, Julian; Sicheritz, Thomas; Robertson, David L.; Marz, Manja
The Third Annual Meeting of the European Virus Bioinformatics Center Journal Article
In: Viruses, vol. 11, no. 5, pp. 420, 2019.
@article{Hufsky:19,
title = {The Third Annual Meeting of the European Virus Bioinformatics Center},
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},
doi = {10.3390/v11050420},
year = {2019},
date = {2019-05-05},
urldate = {2019-05-05},
journal = {Viruses},
volume = {11},
number = {5},
pages = {420},
publisher = {MDPI AG},
abstract = {The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.
2018
Lamkiewicz, Kevin; Barth, Emanuel; Marz, Manja; Ibrahim, Bashar
Identification of potential microRNAs associated with Herpesvirus family based on bioinformatic analysis Journal Article
In: bioRxiv, pp. 417782, 2018.
@article{Lamkiewicz:18,
title = {Identification of potential microRNAs associated with Herpesvirus family based on bioinformatic analysis},
author = {Kevin Lamkiewicz and Emanuel Barth and Manja Marz and Bashar Ibrahim},
doi = {10.1101/417782},
year = {2018},
date = {2018-11-09},
urldate = {2018-11-09},
journal = {bioRxiv},
pages = {417782},
publisher = {Cold Spring Harbor Laboratory},
abstract = {MicroRNAs (miRNAs) are known key regulators of gene expression on posttranscriptional level in many organisms encoded in mammals, plants and also several viral families. To date, no homologous gene of a virus-originated miRNA is known in other organisms. To date, only a few homologous miRNA between two different viruses are known, however, no gene of a virus-originated miRNA is known in any organism of other kingdoms. This can be attributed to the fact that classical miRNA detection approaches such as homology-based predictions fail at viruses due to their highly diverse genomes and their high mutation rate.
Here, we applied the virus-derived precursor miRNA (pre-miRNA) prediction pipeline ViMiFi, which combines information about sequence conservation and machine learning-based approaches, on Human Herpesvirus 7 (HHV7) and Epstein-Barr virus (EBV). ViMiFi was able to predict 61 candidates in EBV, which has 25 known pre-miRNAs. From these 25, ViMiFi identified 20. It was further able to predict 18 candidates in the HHV7 genome, in which no miRNA had been described yet. We also studied the undescribed candidates of both viruses for potential functions and found similarities with human snRNAs and miRNAs from mammals and plants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
MicroRNAs (miRNAs) are known key regulators of gene expression on posttranscriptional level in many organisms encoded in mammals, plants and also several viral families. To date, no homologous gene of a virus-originated miRNA is known in other organisms. To date, only a few homologous miRNA between two different viruses are known, however, no gene of a virus-originated miRNA is known in any organism of other kingdoms. This can be attributed to the fact that classical miRNA detection approaches such as homology-based predictions fail at viruses due to their highly diverse genomes and their high mutation rate.
Here, we applied the virus-derived precursor miRNA (pre-miRNA) prediction pipeline ViMiFi, which combines information about sequence conservation and machine learning-based approaches, on Human Herpesvirus 7 (HHV7) and Epstein-Barr virus (EBV). ViMiFi was able to predict 61 candidates in EBV, which has 25 known pre-miRNAs. From these 25, ViMiFi identified 20. It was further able to predict 18 candidates in the HHV7 genome, in which no miRNA had been described yet. We also studied the undescribed candidates of both viruses for potential functions and found similarities with human snRNAs and miRNAs from mammals and plants.
Here, we applied the virus-derived precursor miRNA (pre-miRNA) prediction pipeline ViMiFi, which combines information about sequence conservation and machine learning-based approaches, on Human Herpesvirus 7 (HHV7) and Epstein-Barr virus (EBV). ViMiFi was able to predict 61 candidates in EBV, which has 25 known pre-miRNAs. From these 25, ViMiFi identified 20. It was further able to predict 18 candidates in the HHV7 genome, in which no miRNA had been described yet. We also studied the undescribed candidates of both viruses for potential functions and found similarities with human snRNAs and miRNAs from mammals and plants.
2017
Madhugiri, Ramakanth; Karl, Nadja; Petersen, Daniel; Lamkiewicz, Kevin; Fricke, Markus; Wend, Ulrike; Scheuer, Robina; Marz, Manja; Ziebuhr, John
Structural and functional conservation of cis-acting RNA elements in coronavirus 5'-terminal genome regions Journal Article
In: Virology, vol. 517, pp. 44–55, 2017.
@article{Madhugiri:18,
title = {Structural and functional conservation of cis-acting RNA elements in coronavirus 5'-terminal genome regions},
author = {Ramakanth Madhugiri and Nadja Karl and Daniel Petersen and Kevin Lamkiewicz and Markus Fricke and Ulrike Wend and Robina Scheuer and Manja Marz and John Ziebuhr},
doi = {10.1016/j.virol.2017.11.025},
year = {2017},
date = {2017-12-06},
urldate = {2017-12-06},
journal = {Virology},
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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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.
Conferences
- 2020 — 4th International Virus Bioinformatics Meeting in Bern, Switzerland
- 2020 — 35th TBI Winterseminar in Bled, Slovenia
- 2019 — 17th Herbstseminar der Bioinformatik in Doubice, Czech Republic
- 2019 — 3rd Annual Meeting of the European Virus Bioinformatics Center in Glasgow, Scotland
- 2019 — 28th Annual Meeting of the Society for Virology in Düsseldorf, Germany
- 2019 — 34th TBI Winterseminar in Bled, Slovenia
- 2018 — 16th Herbstseminar der Bioinformatik in Doubice, Czech Republic
- 2018 — German Conference on Bioinformatics 2018 in Vienna, Austria
- 2018 — Mittelerde-Meeting – 3rd Central German Meeting on Bioinformatics in Mittweida, Germany
- 2018 — 2nd Annual Meeting of the European Virus Bioinformatics Center in Utrecht, Netherlands
- 2018 — 28th Annual Meeting of the Society for Virology in Würzburg, Germany
- 2018 — 33rd TBI Winterseminar in Bled, Slovenia
- 2017 — 15th Herbstseminar der Bioinformatik in Doubice, Czech
- 2017 — German Conference on Bioinformatics 2017 in Tübingen, Germany
- 2017 — Mittelerde-Meeting – 2nd Central German Meeting on Bioinformatics in Leipzig, Germany
- 2017 — HACKEN – Stay Young or Die Trying!, Hackathon in Jena, Germany
- 2017 — 1st Annual Meeting of the European Virus Bioinformatics Center in Jena, Germany
- 2017 — 27th Annual Meeting of the Society for Virology in Marburg, Germany
- 2017 — 32nd TBI Winterseminar in Bled, Slovenia
- 2016 — International Symposium on Bioinformatics Research and Applications in Minsk, Belarus
- 2015 — Recomb-CG in Frankfurt, Germany