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LiSyM network

Overview

This comprises the whole LiSyM network

SEEK ID: https://seek.lisym.org/projects/13

Public web page: http://www.lisym.org

Organisms: Rattus norvegicus, Rattus rattus, Mus musculus, Homo sapiens

FAIRDOM PALs: Max Lüdemann, Matthias König, Vincent Moser, Matthias Reichert, Lutz Brusch, Christian Hudert, Janine Koehncke, Madlen Matz-Soja

Project created: 8th Jun 2017

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Claire Barbieux

Projects: Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network

Institutions: Deutsches Krebsforschungszentrum

Richa Batra

Projects: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network

Institutions: Helmholtz Zentrum München - Institute of Computational Biology

https://orcid.org/0000-0003-3708-0086
Johannes Bausch

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Early Metabolic Injury (LiSyM-EMI - Pillar I), Liver Function Diagnostics (LiSyM-LiFuDi - Pillar IV), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), The Hedgehog Signalling Pathway (LiSyM-JGMMS), LiSyM network, LiSyM Scientific Leadership Team

Institutions: University of Freiburg - Institute of Physics, LiSyM programme directorate

https://orcid.org/0000-0002-1003-1682
Ann-Kristin Becker

Projects: Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM network

Institutions: University Medicine Greifswald - Institute of Bioinformatics

Marie-Luise Berres

Projects: Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network

Institutions: RWTH Aachen University Hospital - Department of Internal Medicine III

SBMC 2018 Book of Abstracts
LiSyM network
No description specified

Creators: None

Contributor: Martin Golebiewski

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LPS stimulated BMDM (ELISA analysis TNF-alpha)
LiSyM network
No description specified

Creator: Sonja Kleeschulte

Contributor: Sonja Kleeschulte

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Key Visual SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Contributor: Johannes Bausch

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Logo SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Contributor: Johannes Bausch

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Banner SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Contributor: Johannes Bausch

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SOP for the exchange of clinical samples and corresponding data between collaboration partners in LiSyM
LiSyM network

The purpose of this document is to define procedures to follow for exchanging the following items between collaboration partners within the LiSyM network:
a) Exchanging samples of human origin obtained from a natural person (i.e. a patient or other human subject).
b) Exchanging material derived from samples of human origin as defined in a).
c) Exchanging associated data describing samples of human origin and derived material as defined in a) and b).
d) Exchanging data derived from samples of human
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Creators: Martin Golebiewski, Frank Lammert, Wolfgang Müller

Contributor: Martin Golebiewski

Benchmark and integration of resources for the estimation of human transcription factor activities
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network

Abstract (Expand)

The prediction of transcription factor (TF) activities from the gene expression of their targets (i.e., TF regulon) is becoming a widely used approach to characterize the functional status of transcriptional … regulatory circuits. Several strategies and data sets have been proposed to link the target genes likely regulated by a TF, each one providing a different level of evidence. The most established ones are (1) manually curated repositories, (2) interactions derived from ChIP-seq binding data, (3) in silico prediction of TF binding on gene promoters, and (4) reverse-engineered regulons from large gene expression data sets. However, it is not known how these different sources of regulons affect the TF activity estimations and, thereby, downstream analysis and interpretation. Here we compared the accuracy and biases of these strategies to define human TF regulons by means of their ability to predict changes in TF activities in three reference benchmark data sets. We assembled a collection of TF–target interactions for 1541 human TFs and evaluated how different molecular and regulatory properties of the TFs, such as the DNA-binding domain, specificities, or mode of interaction with the chromatin, affect the predictions of TF activity. We assessed their coverage and found little overlap on the regulons derived from each strategy and better performance by literature-curated information followed by ChIP-seq data. We provide an integrated resource of all TF–target interactions derived through these strategies, with confidence scores, as a resource for enhanced prediction of TF activities.

Authors: Luz Garcia-Alonso, Christian Holland, Mahmoud M. Ibrahim, Denes Turei, Julio Saez-Rodriguez

Date Published: 1st Aug 2019

Journal: Genome Res.

Robustness and applicability of functional genomics tools on scRNA-seq data
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network

Abstract (Expand)

Many tools have been developed to extract functional and mechanistic insight from bulk transcriptome profiling data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible … to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events, low library sizes and a comparatively large number of samples/cells. It is thus not clear if functional genomics tools established for bulk sequencing can be applied to scRNA-seq in a meaningful way. To address this question, we performed benchmark studies on in silico and in vitro single-cell RNA-seq data. We included the bulk-RNA tools PROGENy, GO enrichment and DoRothEA that estimate pathway and transcription factor (TF) activities, respectively, and compared them against the tools AUCell and metaVIPER, designed for scRNA-seq. For the in silico study we simulated single cells from TF/pathway perturbation bulk RNA-seq experiments. Our simulation strategy guarantees that the information of the original perturbation is preserved while resembling the characteristics of scRNA-seq data. We complemented the in silico data with in vitro scRNA-seq data upon CRISPR-mediated knock-out. Our benchmarks on both the simulated and real data revealed comparable performance to the original bulk data. Additionally, we showed that the TF and pathway activities preserve cell-type specific variability by analysing a mixture sample sequenced with 13 scRNA-seq different protocols. Our analyses suggest that bulk functional genomics tools can be applied to scRNA-seq data, outperforming dedicated single cell tools. Furthermore we provide a benchmark for further methods development by the community.

Authors: Christian Holland, Jovan Tanevski, Jan Gleixner, Manu P. Kumar, Elisabetta Mereu, Javier Perales-Patón, Brian A. Joughin, Oliver Stegle, Douglas A. Lauffenburger, Holger Heyn, Bence Szalai, Julio Saez-Rodriguez

Date Published: No date defined

Journal: Not specified

ECM1 Prevents Activation of Transforming Growth Factor beta, Hepatic Stellate Cells, and Fibrogenesis in Mice.
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network

Abstract (Expand)

BACKGROUND & AIMS: Activation of transforming growth factor beta (TGFB) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanism of TGFB activation are not clear. We … investigated the role of extracellular matrix protein 1 (ECM1), which interacts with extracellular and structural proteins, in TGFB activation in livers of mice. METHODS: We performed studies with e C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Deltahep). ECM1 or soluble TGFB receptor 2 (TGFBR2) were expressed in livers of mice following injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy liver were analyzed by immunohistochemistry and in situ hybridization. RESULTS: ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with alphav integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Deltahep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. CONCLUSIONS: ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.

Authors: W. Fan, T. Liu, W. Chen, Seddik Hammad, T. Longerich, Y. Fu, N. Li, Y. He, C. Liu, Y. Zhang, Q. Lian, Jieling Zhao, C. Yan, L. Li, C. Yi, Z. Ling, L. Ma, Jieling Zhao, H. Xu, P. Wang, M. Cong, H. You, Z. Liu, Y. Wang, J. Chen, D. Li, L. Hui, Steven Dooley, J. Hou, J. Jia, B. Sun

Date Published: 27th Jul 2019

Journal: Gastroenterology

Transfer of regulatory knowledge from human to mouse for functional genomic analysis: Supplementary Document
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network

Abstract (Expand)

Transcriptome profiling followed by differential gene expression analysis often leads to lists of genes that are hard to analyse and interpret. Functional genomic tools are powerful approaches for … downstream analysis, as they summarize the large and noisy gene expression space into a smaller number of biological meaningful features. In particular, methods that estimate the activity of processes by mapping transcripts level to process members are popular. However, footprints of either a pathway or transcription factor (TF) on gene expression show superior performance over mapping-based gene sets. These footprints are largely developed for humans and their usability in the broadly-used model organism Mus musculus is uncertain. Evolutionary conservation of the gene regulatory system suggests that footprints of human pathways and TFs can functionally characterize mice data. In this paper we analyze this hypothesis. We perform a comprehensive benchmark study exploiting two state-of-the-art footprint methods, DoRothEA and an extended version of PROGENy. These methods infer TF and pathway activity, respectively. Our results show that both can recover mouse perturbations, confirming our hypothesis that footprints are conserved between mice and humans. Subsequently, we illustrate the usability of PROGENy and DoRothEA by recovering pathway/TF-disease associations from newly generated disease sets. Additionally, we provide pathway and TF activity scores for a large collection of human and mouse perturbation and disease experiments (2,374). We believe that this resource, available for interactive exploration and download (https://saezlab.shinyapps.io/footprint_scores/), can have broad applications including the study of diseases and therapeutics.

Authors: Christian Holland, Bence Szalai, Julio Saez-Rodriguez

Date Published: No date defined

Journal: Not specified

SECOND EXPOSURE TO ACETAMINOPHEN OVERDOSE IS ASSOCIATED WITH LIVER FIBROSIS IN MICE
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network

Abstract (Expand)

Repeated administration of hepatotoxicants is usually accompanied by liver fibrosis. However, the difference in response as a result of repeated exposures of acetaminophen (APAP) compared to a single … dose is not well-studied. Therefore, in the current study, the liver response after a second dose of APAP was investigated. Adult fasted Balb/C mice were exposed to two toxic doses of 300 mg/kg APAP, which were administered 72 h apart from each other. Subsequently, blood and liver from the treated mice were collected 24 h and 72 h after both APAP admin-istrations. Liver transaminase, i.e. alanine amino transferase (ALT) and aspartate amino transferase (AST) levels revealed that the fulminant liver damage was reduced after the second APAP administration compared to that observed at the same time point after the first treatment. These results correlated with the necrotic areas as indicated by histological analyses. Surprisingly, Picro Sirius Red (PSR) staining showed that the accumulation of extracel-lular matrix after the second dose coincides with the upregulation of some fibrogenic signatures, e.g., alpha smooth muscle actin. Non-targeted liver tissue metabolic profiling indicates that most alterations occur 24 h after the first dose of APAP. However, the levels of most metabolites recover to basal values over time. This organ adaptation process is also confirmed by the upregulation of antioxidative systems like e.g. superoxide dismutase and catalase. From the results, it can be concluded that there is a different response of the liver to APAP toxic doses, if the liver has already been exposed to APAP. A necroinflammatory process followed by a liver regeneration was observed after the first APAP exposure. However, fibrogenesis through the accumulation of extracellular matrix is observed after a second challenge. Therefore, further studies are required to mechanistically understand the so called “liver memory”

Author: Seddik Hammad

Date Published: 6th Feb 2019

Journal: EXCLI

Hedgehog around the clock
The Hedgehog Signalling Pathway (LiSyM-JGMMS), LiSyM PALs, LiSyM network
No description specified

Creator: Madlen Matz-Soja

Contributor: Madlen Matz-Soja

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Pillar II: Outline poster-Jamboree2019-Leipzig
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

Pillar III: AG Dooley Poster-Jamboree2019-Leipzig
Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM network
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

AG Dooley Poster- Jamboree2019-Leipzig
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM network
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

Hünfeld presentation by Peter Jansen
LiSyM network
No description specified

Creator: Peter Jansen

Contributor: Peter Jansen

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e:Med meeting on Systems Medicine

e:Med brings together leading scientists and exceptional young researchers from all over Germany in the emerging field of Systems Medicine. Systems medicine uses interdisciplinary systems-oriented research on diseases to create a basis for understanding complex physiological and pathological processes for development of innovative personalized diagnosis, therapies, and preventive measures. Key to the appropriate analysis and possibly to the modelling of Big Data derived from information levels
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Start Date: 8th Mar 2020

End Date: 10th Mar 2020

Event Website: http://www.sys-med.de/de/meeting/emed-kick-off-2020/

Country:  DE

City: Bonn

21st International Conference on Systems Biology (ICSB 2020)

ICSB is one of the largest international conferences on systems biology. Since the first conference in Tokyo in 2000, which was organized by Dr. Hiroaki Kitano, it has been held annually in different countries.

Start Date: 10th Oct 2020

End Date: 16th Oct 2020

Event Website: http://icsb2020.bioscience-ct.net/

Country:  US

City: Hartford, Connecticut

HARMONY 2020 (Hackathon on Resources for Modeling in Biology)

The Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology, synthetic biology and related fields. HARMONY is a codefest-type meeting, with a focus on development of the standards, interoperability and infrastructure. There are generally not many general discussions or oral presentations during HARMONY; instead, the time is devoted to allowing hands-on hacking and interaction between people
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Start Date: 9th Mar 2020

End Date: 13th Mar 2020

Event Website: http://co.mbine.org/events

Country:  GB

City: Hinxton, Cambridge

COMBINE 2020 (Computational Modeling in Biology Network Meeting)

The "Computational Modeling in Biology" Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology, systems medicine, synthetic biology and related fields. COMBINE 2020 will be a workshop-style event with invited lectures, oral presentations and posters, but also reserving enough time for afternoon breakout sessions to discuss topics around data and model standardization and integration, as well as harmonization and further
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Start Date: 6th Oct 2020

End Date: 9th Oct 2020

Event Website: http://co.mbine.org/events

Country:  US

City: Farmington, Connecticut

COMBINE & de.NBI Tutorial: Modelling and Simulation Tools in Systems Biology

This tutorial workshop is a satellite of the 20th International Conference on Systems Biology (ICSB).
Participants will learn how to set up computer models of biological systems (e.g. metabolic or signalling networks) using experimental kinetic data and how to simulate them in different systems biology platforms. Hands-on sessions, lectures and software demonstrations will be included, providing attendees with the necessary skills to access experimental kinetics data from available resources, to
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Start Date: 31st Oct 2019

End Date: 31st Oct 2019

Event Website: http://co.mbine.org/events/tutorial2019

Country:  JP

City: Onna, Okinawa

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