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Computational Systems Genetics Group

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Contents

Prof. Dr. Susanne Gerber

Personal information

2001-2004

Bachelor of Science in Bioinformatics, Free University of Berlin, Germany

2004-2007

Master of Science in Bioinformatics, Free University of Berlin

2007-2011

Ph.D. studies in Theoretical Biophysics, Humboldt University of Berlin

2011- 09/2015

Postdoc at the Faculty of Informatics, Universita della Svizzera italiana, Lugano, Switzerland

10/2015-05/2020

Assistant Professor for Bioinformatics, Faculty of Biology and Center for Computational Sciences, Johannes Gutenberg University Mainz

Since 05/2020

Full Professor for Computational Genomics and Bioinformatics, Institute of Human Genetics, University Medical Center Mainz

Lab Members

Prof. Dr. Gerber
Prof. Dr. Susanne Gerber
Funktionen: Research Group Leader

+49 (0)6131 39 27331
sugerber@uni-mainz.de

Butto
Tamer Butto
Funktionen: PhD Student
Qualifikationen: MSc. Genetics and Microbiology

06131 39 20141
t.butto@imb-mainz.de

Caliendo
Cosima Caliendo
Funktionen: PhD Student
Qualifikationen: MSc. Applied bioinformatics

06131 39 27144
caliendo@uni-mainz.de

Hewel
Charlotte Hewel
Funktionen: PhD Student
Qualifikationen: MSc. Anthropology

06131 39 27144
chhewel@uni-mainz.de

Klingenberg
Susanne Klingenberg
Funktionen: PhD Student
Qualifikationen: Dipl. Biology

06131 39 27144
klingens@uni-mainz.de

Mungikar
Kanak Mungikar
Funktionen: PhD Student
Qualifikationen: MSc. Bioinformatics

06131 39 20141
kanakmungikar@gmail.com

Navandar
Mohit Navandar
Funktionen: PhD Student
Qualifikationen: MSc. Bioinformatics

06131 39 20141
M.Navandar@imb-mainz.de

Ruffini
Nicolas Ruffini
Funktionen: PhD Student
Qualifikationen: MSc. Applied bioinformatics

ruffini@uni-mainz.de

Sys
Stanislav Sys
Funktionen: PhD Student
Qualifikationen: MSc. Applied bioinformatics

stsys@uni-mainz.de

Todorov
Hristo Todorov
Funktionen: Research Assistant
Qualifikationen: MSc. Bioinformatics

06131 39 20141
hristo.todorov@uni-mainz.de

Weißbach
Stephan Weißbach
Funktionen: PhD Student
Qualifikationen: MSc. Applied bioinformatics

s.weissbach@uni-mainz.de

Wierczeiko
Anna Wierczeiko
Funktionen: PhD Student
Qualifikationen: MSc. Applied bioinformatics

06131 39 27144
anna.wierczeiko@lir-mainz.de

Research Projects

Deciphering the epigenetic basis of resilience

This study examines the molecular mechanisms regulating neuronal function in stress susceptible and resilient mice following chronic social defeat (CSD) by comparing the transcriptomes of activated cells in selected brain regions using RNA-seq. In addition, using the assay for transposase-accessible chromatin followed by high-throughput sequencing (ATAC-seq) and bisulfite sequencing (Bis-seq), we monitor the global changes in chromatin accessibility and DNA methylation signatures that alter the functional states of neurons in response to stress.

Using Multi-Omics Integration to explore the Molecular Background of Stress Resilience

Resilience is the ability to cope with stress or to quickly recover to pre-crisis state after being exposed to extreme stress. As the human mental status is highly diverse, there are presumably many different molecular mechanisms underlying resilience. The main goal of this project is the identification of common molecular patterns between resilient individuals by analyzing and integrating various omics levels, e.g. transcriptomics, proteomics, methylomics and metagenomics. By subsequently selecting important features within the large amount of data, we aim to give a less complex view on the dynamic process of resilience. This work is funded by the Leibniz Institute for Resilience Research (LIR) (https://lir-mainz.de/) and in collaboration with the Frauenhofer ITWM (https://www.itwm.fraunhofer.de/). The majority of the underlying data sets originate from the MARP (https://marpstudie.de/) and LORA (https://lora-studie.de/) studies from the LIR.

Reliability of Next Generation Sequencing Machines and Bioinformatic Processing Pipelines

Next Generation Sequencing (NGS) is commonly used to gain insights into various questions from biology and medicine. This approach depends heavily on reliable and accurate data. In this project, we investigated the impact of different sequencing machines and their respective bioinformatic processing pipelines on the resulting variant call data.

We examined 99 individuals, which were sequenced three times with three different sequencers and were post-processed with different bioinformatic processing pipelines. The analysis showed considerable heterogeneity between the three sequencing cohorts. Even after applying non-specific filters like MAF and HWE, which are the standard for quality filtering and noise reduction in NGS cohorts, differences of several thousand variants per individual remained. This illustrates the need for continued refinement of both laboratory and computational analysis methods in order to achieve bias-free data.

BIG data integration of genetic and epigenetic variations in neurodegenerative diseases

To gain a better understanding of the global mechanisms underlying neurodegeneration we use supercomputing facilities and recently developed High-Performance Computing methods in multivariate Genome Wide Association Studies (GWAS) for the extraction of global patterns. Analysis includes genetic as well as epigenetic and transcriptional aspects, underlying neurodegenerative diseases i.e. Alzheimer’s, Parkinson’s and Huntington’s disease. Via a trans-Omics evaluation followed by in silico modeling we hope to extract core (biochemical) networks across multiple omic-layers (genome, transcriptome, methylome).

Optimization of the Calcium Imaging Analysis Pipeline

Calcium Imaging Analysis enables researchers to track the activity of hundreds and thousands of neurons within the brains of living animals. However, analyzing this huge amount of data raises some difficulties. Together with the group of Prof. Dr. Albrecht Stroh (http://www.strohlab.com/) and in collaboration with the Fraunhofer ITWM, we are following the goal of improving and accelerating the analysis of calcium imaging data, starting with the automatic marking of neurons in the generated image files using deep learning. By optimizing and simplifying the application through user-friendly interfaces of the entire analysis pipeline, the effort and time required for Calcium Imaging Analyses can be drastically reduced and will also be less dependent on personal decisions.

Uncovering neural subpopulations and transcriptional networks underlying stress resilience

Chronic stress and traumatic events have major impact on human psychological health and the manifestation of stress-related mental disorders. The majority of individuals encountering such stress are able to surmount it and therefore are resilient, while a small portion of the population manifest mood disorders, such as anxiety, social dysfunction and depression. However, very little is known about the rewiring of gene regulatory programs underlying these processes.

The chronic social defeat (CSD) is known to evoke responses in distinct brain areas, especially hippocampus, prefrontal cortex, and amygdala. In this project, we conduct single-cell RNA-seq from the hippocampus and basolateral amygdala of socially defeated mice from resilient and non-resilient groups and use this approach not only to reveal distinct neural subpopulations in response to CSD, but also to uncover whether these subpopulations behave differently in resilient and non-resilient mice. Using extensive computational analysis, we aim at characterizing gene expression programs that operate at single cell level in response to stress and how such networks are differentially (re)programmed between resilient and non-resilient mice.

Characterization of gut microbiota composition using 16S rRNA sequencing

Sequencing of the 16S ribosomal RNA marker gene (16S rRNA) provides a cost-effective method to characterize the bacterial composition of biological or ecological samples. In experimental animal studies, this approach allows investigating the impact of factors such as pharmacological treatment or diet on commensal microbiota. Another crucial research question is whether shifts in gut bacterial composition are associated with disease phenotypes. In ongoing collaborations with experimental groups, we focus on the bioinformatical and biostatistical analysis of 16S sequencing data. This requires applying ordination techniques which can handle distance measures appropriate for ecological data such as principal coordinates analysis or correspondence analysis. Furthermore, no consensus on the optimal statistical technique for differential abundance analysis exists. Therefore, this decision needs to be based on considerations such as sample size, experimental setup and specific research question.

Selected Publications

  • Susanne Gerber, Lukas Pospisil, Mohit Navandar and Illia Horenko:Low-cost scalable discretization, prediction and feature selection for complex systems, Science Advances, Vol. 6, no. 5, eaaw0961 DOI: 10.1126/sciadv.aaw0961 (2020).
  • Laura Domingo-Rodriguez, Inigo Ruiz de Azua, Eduardo Dominguez, Eric Senabre, Irene Serra,Sami Kummer, Mohit Navandar, Sarah Baddenhausen, Clementine Hofmann, Raul Andero, Susanne Gerber, Marta Navarrete, Mara Dierssen, Beat Lutz, Elena Martín-García & Rafael Maldonado: A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nature Communications 11, 782 (2020). https://doi.org/10.1038/s41467-020-14458-y
  • Caroline Fischer, Heiko Endle, Lana Schumann, Annett Wilken-Schmitz, Julia Kaiser, Susanne Gerber, Christina F. Vogelaar, Mirko H.H. Schmidt, Robert Nitsch, Isabel Snodgrass, Dominique Thomas, Johannes Vogt, Irmgard Tegeder. Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2. Cellular and Molecular Life Sciences doi.org/10.1007/s00018-020-03553-4 (2020).
  • Klytaimnistra Kiouptsi, Giulia Pontarollo, Hristo Todorov, Johannes Braun, Sven Jäckel, Thomas Koeck, Franziska Bayer, Cornelia Karwot, Angelica Karpi, Susanne Gerber, Yvonne Jansen, Philipp Wild, Wolfram Ruf, Andreas Daiber, Emiel van der Vorst, Christian Weber, Yvonne Döring, Christoph Reinhardt. Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice.  Gut Microbes www.tandfonline.com/doi/full/10.1080/19490976.2020.1767463 (2020).
  • Malena dos Santos Guilherme, Hristo Todorov, Carina Osterhof, Anton Möllerke, Kristina Cub, Thomas Hankeln, Susanne Gerber, Kristina Endres: Impact of acute and chronic amyloid-β peptide exposure on gut microbial commensals in the mouse.  Frontiers in Microbiology 11:1008. doi: 10.3389/fmicb.2020.01008 (2020).
  • Hristo Todorov, Emily Searle-White and Susanne Gerber. Applying univariate vs. multivariate statistics to investigate therapeutic efficacy in (pre)clinical trials: A Monte Carlo simulation study on the example of a controlled preclinical neurotrauma trial. PLOS ONE, 15(3): e0230798; doi.org/10.1371/journal.pone.0230798 (2020).
  • Hristo Todorov, Bettina Kollar, Franziska Bayer, Inês Brandão, Amrit Mann, Julia Mohr, Giulia Pontarollo, Henning Formes, Roland Stauber, Jens M. Kittner, Kristina Endres, Bernhard Watzer, Wolfgang Andreas Nockher, Felix Sommer, Susanne Gerber and Christoph Reinhardt. Alpha-Linolenic Acid-Rich Diet Influences Microbiota Composition and Villus Morphology of the Mouse Small Intestine. Nutrients. 12, 732; doi:10.3390/nu12030732. (2020).
  • Marlon Wendelmuth, Michael Willam, Hristo Todorov, Konstantin Radyushkin, Susanne Gerber and Susann Schweiger. Dynamic longitudinal behavior in animals exposed to chronic social defeat stress.  PLOS ONE. 15(7): e0235268 (2020).
  • Charlotte Hewel, Julia Kaiser, Anna Wierczeiko, Jan Linke, Christoph Reinhardt, Kristina Endres and Susanne Gerber: Common miRNA patterns of Alzheimers disease and Parkinsons disease and their putative impact on commensal gut microbiota. Frontiers in Neuroscience, doi: 10.3389/fnins.2019.00113  (2019)
  • Susanne Gerber, Simon Olsson, Frank Noe and Illia Horenko: A scalable approach to the computation of invariant measures for high-dimensional Markovian systems. Nature Scientific Reports, 8,  Article number: 1796, doi:10.1038/s41598-018-19863-4 (2018)
  • Hristo Todorov, David Fournierand Susanne Gerber: Principal components analysis: theory and application to gene expression data analysis, Genomics and Computational Biology,  4(2) p. e100041, jan. 2018. ISSN 2365-7154 (2018)
  • Anna Wierczeiko, David Fournier, Hristo Todorov, Susanne Klingenberg, Kristina Endres and Susanne Gerber: Decoupling of DNA methylation status and gene expression levels in aging individuals,  Genomics and Computational Biology, 4(2) p.e100040, jan. 2018. ISSN 2365-7154 (2018).
  • Stanislav J. Sys, David Fournier, Illia Horenko, Kristina Endres and Susanne Gerber: Dynamics of SNP associations in relation to Alzheimer’s Disease captured with a new measure of linkage disequilibrium. Genomics and Computational Biology, 4(2) p. e100045, jan. 2018. ISSN 2365-7154 (2018).
  • Susanne Gerber and Illia Horenko: Towards a direct and scalable identification of reduced models for categorical processes, Proceedings of the National Academy of Sciences of the United States of America - (PNAS),114 (19) 4863-4868,doi:10.1073/pnas.1612619114 (2017).
  • Susanne Gerber, Martina Fröhlich, Hella Lichtenberg-Fraté, Sergey Shabala, Lana Shabala and Edda Klipp:  A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae PLoS Comput. Biol. 12 (1), e1004703. doi: 10.1371/journal.pcbi.1004703, PMID: 26815455  (2016).
  • Susanne Gerber and Illia Horenko:  Improving clustering by imposing network information. Science Advances 1(7), e1500163; DOI: 10.1126/sciadv.1500163  (2015).
  • Susanne Gerber and Illia Horenko: On inference of causality for discrete state models in multiscale context.  Proceedings of the National Academy of Sciences of the United States of America -  111 (41) 14651-14656, doi:10.1073/pnas.1410404111,(2014).

Full list of publications:

https://csg.uni-mainz.de/search/