
Detecting time-resolved and virulence-associated host responses to viral infection
Understanding the cell’s transcriptional response to virus infections is crucial for comprehending the host’s molecular defence, the pathogen’s strategies to circumvent these mechanisms, and hence the viral capability to cause severe disease (i.e. their virulence). However, currently available methods are not sufficient to accurately determine the cellular transcription response, especially for viruses that cause a global host cell shut-off. In these cases, available computational read normalisation strategies prohibit an accurate analysis of differential gene expression. Moreover, current off-the-shelf methods also cannot assess the expression of all relevant transcript classes, in particular the highly repetitive transposable elements (TEs) that have been reported to trigger innate immunity in virus-infected cells. Currently used analysis pipelines do not yet enable the assessment of individual TE copy expression.
Thus, we aim to develop tools for (i) normalisation of reads to accurately measure the host transcription shut-off imposed by viruses and (ii) mapping expression of individual TE copies. Moreover, we aim to (iii) combine these methods into a tool to systematically analyse and cluster expression time series to characterise expression trajectories and infer regulatory interactions during viral infections. We expect that the development and implementation of the proposed software will subsequently enable us to improve the transcriptome-based prediction of a pathogen’s virulence.
- WP 1: Shut-off-corrected comparison of recurring expression profiles (Weber/Hoffmann)
- WP 2: Locus-specific expression of endogenous retroviruses in response to viral infection (Hoffmann/Weber)
- WP 3: Integrative analysis and transcriptome-based virulence prediction (Hoffmann/Weber)
Team Members
N. N.
Doctoral Researcher
N. N.
Doctoral Researcher
Project-Specific Publications
2025
Wiechens, Elina; Vigliotti, Flavia; Siniuk, Kanstantsin; Schwarz, Robert; Schwab, Katjana; Riege, Konstantin; Bömmel, Alena; Görlich, Ivonne; Bens, Martin; Sahm, Arne; Groth, Marco; Sammons, Morgan A; Loewer, Alexander; Hoffmann, Steve; Fischer, Martin
Gene regulation by convergent promoters Journal Article
In: Nat Genet, vol. 57, iss. 1, no. 1, pp. 206-217, 2025.
@article{Wiechens:25,
title = {Gene regulation by convergent promoters},
author = {Elina Wiechens and Flavia Vigliotti and Kanstantsin Siniuk and Robert Schwarz and Katjana Schwab and Konstantin Riege and Alena Bömmel and Ivonne Görlich and Martin Bens and Arne Sahm and Marco Groth and Morgan A Sammons and Alexander Loewer and Steve Hoffmann and Martin Fischer},
url = {https://pubmed.ncbi.nlm.nih.gov/39779959/},
doi = {10.1038/s41588-024-02025-w},
year = {2025},
date = {2025-01-01},
urldate = {2025-01-01},
journal = {Nat Genet},
volume = {57},
number = {1},
issue = {1},
pages = {206-217},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2024
Hofmann, Nina; Bartkuhn, Marek; Becker, Stephan; Biedenkopf, Nadine; Böttcher-Friebertshäuser, Eva; Brinkrolf, Karina; Dietzel, Erik; Fehling, Sarah Katharina; Goesmann, Alexander; Heindl, Miriam Ruth; Hoffmann, Simone; Karl, Nadja; Maisner, Andrea; Mostafa, Ahmed; Kornecki, Laura; Müller-Kräuter, Helena; Müller-Ruttloff, Christin; Nist, Andrea; Pleschka, Stephan; Sauerhering, Lucie; Stiewe, Thorsten; Strecker, Thomas; Wilhelm, Jochen; Wuerth, Jennifer D.; Ziebuhr, John; Weber, Friedemann; Schmitz, M. Lienhard
Distinct negative-sense RNA viruses induce a common set of transcripts encoding proteins forming an extensive network. Journal Article
In: J Virol, vol. 98, iss. 10, no. 10, pp. e0093524, 2024.
@article{Hofmann:24,
title = {Distinct negative-sense RNA viruses induce a common set of transcripts encoding proteins forming an extensive network.},
author = {Nina Hofmann and Marek Bartkuhn and Stephan Becker and Nadine Biedenkopf and Eva Böttcher-Friebertshäuser and Karina Brinkrolf and Erik Dietzel and Sarah Katharina Fehling and Alexander Goesmann and Miriam Ruth Heindl and Simone Hoffmann and Nadja Karl and Andrea Maisner and Ahmed Mostafa and Laura Kornecki and Helena Müller-Kräuter and Christin Müller-Ruttloff and Andrea Nist and Stephan Pleschka and Lucie Sauerhering and Thorsten Stiewe and Thomas Strecker and Jochen Wilhelm and Jennifer D. Wuerth and John Ziebuhr and Friedemann Weber and M. Lienhard Schmitz},
url = {https://pubmed.ncbi.nlm.nih.gov/39283124/},
doi = {10.1128/jvi.00935-24},
year = {2024},
date = {2024-10-01},
urldate = {2024-10-01},
journal = {J Virol},
volume = {98},
number = {10},
issue = {10},
pages = {e0093524},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Olecka, Maja; Bömmel, Alena; Best, Lena; Haase, Madlen; Foerste, Silke; Riege, Konstantin; Dost, Thomas; Flor, Stefano; Witte, Otto W; Franzenburg, Sören; Groth, Marco; Eyss, Björn; Kaleta, Christoph; Frahm, Christiane; Hoffmann, Steve
Nonlinear DNA methylation trajectories in aging male mice Journal Article
In: Nat Commun, vol. 15, iss. 1, no. 1, pp. 3074, 2024, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking).
@article{Olecka:24,
title = {Nonlinear DNA methylation trajectories in aging male mice},
author = {Maja Olecka and Alena Bömmel and Lena Best and Madlen Haase and Silke Foerste and Konstantin Riege and Thomas Dost and Stefano Flor and Otto W Witte and Sören Franzenburg and Marco Groth and Björn Eyss and Christoph Kaleta and Christiane Frahm and Steve Hoffmann},
url = {https://pubmed.ncbi.nlm.nih.gov/38594255/},
doi = {10.1038/s41467-024-47316-2},
issn = {2041-1723 (Electronic)
2041-1723 (Linking)},
year = {2024},
date = {2024-04-01},
journal = {Nat Commun},
volume = {15},
number = {1},
issue = {1},
pages = {3074},
keywords = {},
pubstate = {epublish},
tppubtype = {article}
}
2022
Schwarz, Robert; Koch, Philipp; Wilbrandt, Jeanne; Hoffmann, Steve
Locus-specific expression analysis of transposable elements. Journal Article
In: Brief Bioinform, vol. 23, iss. 1, 2022, ISSN: 1477-4054.
@article{Schwarz:22,
title = {Locus-specific expression analysis of transposable elements.},
author = {Robert Schwarz and Philipp Koch and Jeanne Wilbrandt and Steve Hoffmann},
doi = {10.1093/bib/bbab417},
issn = {1477-4054},
year = {2022},
date = {2022-01-01},
journal = {Brief Bioinform},
volume = {23},
issue = {1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2020
Schoen, Andreas; Lau, Simone; Verbruggen, Paul; Weber, Friedemann
Elongin C contributes to RNA polymerase II degradation by the interferon antagonist NSs of La Crosse Orthobunyavirus Journal Article
In: J Virol, vol. 94, iss. 7, 2020.
@article{Schoen:20,
title = {Elongin C contributes to RNA polymerase II degradation by the interferon antagonist NSs of La Crosse Orthobunyavirus},
author = {Andreas Schoen and Simone Lau and Paul Verbruggen and Friedemann Weber},
doi = {10.1128/JVI.02134-19},
year = {2020},
date = {2020-01-01},
journal = {J Virol},
volume = {94},
issue = {7},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2019
Hölzer, Martin; Schoen, Andreas; Wulle, Julia; Müller, Marcel A; Drosten, Christian; Marz, Manja; Weber, Friedemann
Virus- and interferon alpha-induced transcriptomes of cells from the microbat emphMyotis daubentonii Journal Article
In: iScience, vol. 19, pp. 647-661, 2019, ISSN: 2589-0042.
@article{Hoelzer:19:bats,
title = {Virus- and interferon alpha-induced transcriptomes of cells from the microbat emphMyotis daubentonii},
author = {Martin Hölzer and Andreas Schoen and Julia Wulle and Marcel A Müller and Christian Drosten and Manja Marz and Friedemann Weber},
url = {https://doi.org/10.1016/j.isci.2019.08.016},
doi = {10.1016/j.isci.2019.08.016},
issn = {2589-0042},
year = {2019},
date = {2019-09-27},
journal = {iScience},
volume = {19},
pages = {647-661},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2018
Wuerth, Jennifer Deborah; Habjan, Matthias; Wulle, Julia; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann
In: J Virol, vol. 92, iss. 23, 2018.
@article{Wuerth:18,
title = {NSs protein of sandfly fever Sicilian phlebovirus counteracts interferon (IFN) induction by masking the DNA-binding domain of IFN regulatory factor 3},
author = {Jennifer Deborah Wuerth and Matthias Habjan and Julia Wulle and Giulio Superti-Furga and Andreas Pichlmair and Friedemann Weber},
doi = {10.1128/jvi.01202-18},
year = {2018},
date = {2018-01-01},
journal = {J Virol},
volume = {92},
issue = {23},
publisher = {American Society for Microbiology},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2014
Hoffmann, Steve; Otto, Christian; Doose, Gero; Tanzer, Andrea; Langenberger, David; Christ, Sabina; Kunz, Manfred; Holdt, Lesca M; Teupser, Daniel; Hackermüller, Jörg; Stadler, Peter F
A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection. Journal Article
In: Genome Biol, vol. 15, iss. 2, pp. R34, 2014, ISSN: 1474-760X.
@article{Hoffmann:14,
title = {A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection.},
author = {Steve Hoffmann and Christian Otto and Gero Doose and Andrea Tanzer and David Langenberger and Sabina Christ and Manfred Kunz and Lesca M Holdt and Daniel Teupser and Jörg Hackermüller and Peter F Stadler},
doi = {10.1186/gb-2014-15-2-r34},
issn = {1474-760X},
year = {2014},
date = {2014-01-01},
journal = {Genome Biol},
volume = {15},
issue = {2},
pages = {R34},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann
Virulence factor NSs of Rift Valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH Journal Article
In: J Virol, vol. 88, no. 6, pp. 3464-3473, 2014.
@article{Kainulainen:14,
title = {Virulence factor NSs of Rift Valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH},
author = {Markus Kainulainen and Matthias Habjan and Philipp Hubel and Laura Busch and Simone Lau and Jacques Colinge and Giulio Superti-Furga and Andreas Pichlmair and Friedemann Weber},
doi = {10.1128/jvi.02914-13},
year = {2014},
date = {2014-01-01},
journal = {J Virol},
volume = {88},
number = {6},
pages = {3464-3473},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2009
Hoffmann, Steve; Otto, Christian; Kurtz, Stefan; Sharma, Cynthia M; Khaitovich, Philipp; Vogel, Jörg; Stadler, Peter F; Hackermüller, Jörg
Fast mapping of short sequences with mismatches, insertions and deletions using index structures. Journal Article
In: PLoS Comput Biol, vol. 5, iss. 9, pp. e1000502, 2009, ISSN: 1553-7358.
@article{Hoffmann:09,
title = {Fast mapping of short sequences with mismatches, insertions and deletions using index structures.},
author = {Steve Hoffmann and Christian Otto and Stefan Kurtz and Cynthia M Sharma and Philipp Khaitovich and Jörg Vogel and Peter F Stadler and Jörg Hackermüller},
doi = {10.1371/journal.pcbi.1000502},
issn = {1553-7358},
year = {2009},
date = {2009-01-01},
journal = {PLoS Comput Biol},
volume = {5},
issue = {9},
pages = {e1000502},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
