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LiSyM network

Overview

This comprises the whole LiSyM network

Programme: LiSyM: Liver Systems Medicine

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 start date: 1st Jan 2016

Related items

Claire Barbieux

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

Institutions: Deutsches Krebsforschungszentrum

Richa Batra

Projects: LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), 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), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

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

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

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

Institutions: University Medicine Greifswald - Institute of Bioinformatics

Nikolaus Berndt

Projects: LiSyM-Krebs Partnering, LiSyM network, LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), LiSyM-Krebs

Institutions: Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Computational Systems Biochemistry Group

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SBMC 2018 Book of Abstracts
LiSyM network
No description specified

Creators: None

Submitter: Martin Golebiewski

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

Creator: Sonja Kleeschulte

Submitter: Sonja Kleeschulte

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Key Visual SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Submitter: Johannes Bausch

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Logo SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Submitter: Johannes Bausch

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Banner SBMC 2018 Bremen
LiSyM network
No description specified

Creator: Johannes Bausch

Submitter: Johannes Bausch

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Spatio-temporal model of YAP activation during liver regeneration
LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network

For the spatio-temporal dynamics of bile transport, bile canalicular dilation, mechanical stimulation and transduction of YAP signaling during liver regeneration see the open access publication and its appendix:
Meyer et al. (2020) Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration. Molecular Systems Biology 16:e8985. https://doi.org/10.15252/msb.20198985

The model format is MorpheusML that can readily be loaded and run in the free and open source software
...

Creator: Lutz Brusch

Submitter: Lutz Brusch

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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

Submitter: Martin Golebiewski

Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data
LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network

Abstract (Expand)

Background Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome 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 and low library sizes. It is thus not clear if functional TF and pathway analysis tools established for bulk sequencing can be applied to scRNA-seq in a meaningful way. Results To address this question, we perform benchmark studies on simulated and real scRNA-seq data. We include the bulk-RNA tools PROGENy, GO enrichment, and DoRothEA that estimate pathway and transcription factor (TF) activities, respectively, and compare them against the tools SCENIC/AUCell and metaVIPER, designed for scRNA-seq. For the in silico study, we simulate single cells from TF/pathway perturbation bulk RNA-seq experiments. We complement the simulated data with real scRNA-seq data upon CRISPR-mediated knock-out. Our benchmarks on simulated and real data reveal comparable performance to the original bulk data. Additionally, we show that the TF and pathway activities preserve cell type-specific variability by analyzing a mixture sample sequenced with 13 scRNA-seq protocols. We also provide the benchmark data for further use by the community. Conclusions Our analyses suggest that bulk-based functional analysis tools that use manually curated footprint gene sets can be applied to scRNA-seq data, partially outperforming dedicated single-cell tools. Furthermore, we find that the performance of functional analysis tools is more sensitive to the gene sets than to the statistic used.

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

Date Published: 1st Dec 2020

Publication Type: Journal

Chronic Disruption of the Late Cholesterol Synthesis Leads to Female-Prevalent Liver Cancer.
The Hedgehog Signalling Pathway (LiSyM-JGMMS), LiSyM network

Abstract (Expand)

While the role of cholesterol in liver carcinogenesis remains controversial, hepatocellular carcinoma generally prevails in males. Herein, we uncover pathways of female-prevalent progression to … hepatocellular carcinoma due to chronic repression of cholesterogenic lanosterol 14alpha-demethylase (CYP51) in hepatocytes. Tumors develop in knock-out mice after year one, with 2:1 prevalence in females. Metabolic and transcription factor networks were deduced from the liver transcriptome data, combined by sterol metabolite and blood parameter analyses, and interpreted with relevance to humans. Female knock-outs show increased plasma cholesterol and HDL, dampened lipid-related transcription factors FXR, LXRalpha:RXRalpha, and importantly, crosstalk between reduced LXRalpha and activated TGF-beta signalling, indicating a higher susceptibility to HCC in aging females. PI3K/Akt signalling and ECM-receptor interaction are common pathways that are disturbed by sex-specific altered genes. Additionally, transcription factors (SOX9)2 and PPARalpha were recognized as important for female hepatocarcinogenesis, while overexpressed Cd36, a target of nuclear receptor RORC, is a new male-related regulator of ECM-receptor signalling in hepatocarcinogenesis. In conclusion, we uncover the sex-dependent metabolic reprogramming of cholesterol-related pathways that predispose for hepatocarcinogenesis in aging females. This is important in light of increased incidence of liver cancers in post-menopausal women.

Authors: K. B. Cokan, Z. Urlep, G. Lorbek, M. Matz-Soja, C. Skubic, M. Perse, J. Jeruc, P. Juvan, T. Rezen, D. Rozman

Date Published: 9th Nov 2020

Publication Type: Journal

Expression of TLR-2 in hepatocellular carcinoma is associated with tumour proliferation, angiogenesis and Caspase-3 expression.
LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network

Abstract (Expand)

AIMS: Unlike other Toll-like receptors (TLRs), the role of toll like receptor 2 (TLR-2) in the pathogenesis of chronic liver disease and hepatocellular carcinoma (HCC) is not well studied. We, therefore, … set out to investigate the expression of TLR-2 in different chronic liver disease states along with other markers of cell death, cellular proliferation and tissue vascularisation METHODS AND RESULTS: Immunohistochemistry was performed on liver tissue microarrays comprising hepatitis, cirrhosis and HCC patient samples using antibodies against TLR-2, Ki-67, Caspase-3 and VEGF. This was done in order to characterise receptor expression and translocation, apoptosis, cell proliferation and vascularisation. Cytoplasmic TLR-2 expression was found to be weak in 5/8 normal liver cases, 10/19 hepatitis cases and 8/21 cirrhosis patients. Moderate to strong TLR-2 expression was observed in some cases of hepatitis and cirrhosis. Both, nuclear and cytoplasmic TLR-2 expression was present in HCC with weak intensity in 11/41 cases, and moderate to strong staining in 19/41 cases. Eleven HCC cases were TLR-2 negative. Surprisingly, both cytoplasmic and nuclear TLR-2 expression in HCC were found to significantly correlate with proliferative index (r = 0.24 and 0.37), Caspase-3 expression (r = 0.27 and 0.38) and vascularisation (r = 0.56 and 0.23). Further, nuclear TLR-2 localisation was predominant in HCC, whereas cytoplasmic expression was more prevalent in hepatitis and cirrhosis. Functionally, treatment of HUH7 HCC cells with a TLR-2 agonist induced the expression of cellular proliferation and vascularisation markers CD34 and VEGF. CONCLUSIONS: Our results demonstrate a positive correlation between the expression of TLR-2 and other markers of proliferation and vascularisation in HCC which suggests a possible role for TLR-2 in HCC pathogenesis.

Authors: F. E. A. Mohamed, S. Hammad, T. V. Luong, B. Dewidar, R. Al-Jehani, N. Davies, S. Dooley, R. Jalan

Date Published: 25th Jul 2020

Publication Type: Journal

Towards standardization guidelines for in silico approaches in personalized medicine.
LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM network

Abstract (Expand)

Despite the ever-progressing technological advances in producing data in health and clinical research, the generation of new knowledge for medical benefits through advanced analytics still lags behind … its full potential. Reasons for this obstacle are the inherent heterogeneity of data sources and the lack of broadly accepted standards. Further hurdles are associated with legal and ethical issues surrounding the use of personal/patient data across disciplines and borders. Consequently, there is a need for broadly applicable standards compliant with legal and ethical regulations that allow interpretation of heterogeneous health data through in silico methodologies to advance personalized medicine. To tackle these standardization challenges, the Horizon2020 Coordinating and Support Action EU-STANDS4PM initiated an EU-wide mapping process to evaluate strategies for data integration and data-driven in silico modelling approaches to develop standards, recommendations and guidelines for personalized medicine. A first step towards this goal is a broad stakeholder consultation process initiated by an EU-STANDS4PM workshop at the annual COMBINE meeting (COMBINE 2019 workshop report in same issue). This forum analysed the status quo of data and model standards and reflected on possibilities as well as challenges for cross-domain data integration to facilitate in silico modelling approaches for personalized medicine.

Authors: S. Brunak, C. Bjerre Collin, K. Eva O Cathaoir, M. Golebiewski, M. Kirschner, I. Kockum, H. Moser, D. Waltemath

Date Published: 24th Jul 2020

Publication Type: Journal

SBML Level 3: an extensible format for the exchange and reuse of biological models
Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM network

Abstract (Expand)

Systems biology has experienced dramatic growth in the number, size and complexity of computational models describing biology. To reproduce simulation results and reuse models, researchers need to … exchange precise and unambiguous descriptions of model structure and meaning. SBML (the Systems Biology Markup Language) is a community-developed format for this purpose. The latest edition, called SBML Level 3, has a modular structure, with a core suited to representing reaction-based models, and packages that extend the core with features suited for a variety of model types. Examples include constraint-based models, reaction-diffusion models, logical network models, and rule-based models. SBML and its rich software ecosystem have transformed the way systems biologists build and interact with models, and has played an important role in increasing model interoperability and reuse over the past two decades. More recently, a rise of multiscale models of whole cells and organs, and new data sources such as single cells measurements and live imaging, have precipitated new ways of integrating data and models. SBML Level 3 provides the foundation needed to support this evolution.

Authors: SM Keating, D Waltemath, M König, F Zhang, A Dräger, C Chaouiya, FT Bergmann, A Finney, CS Gillespie, T Helikar, S Hoops, RS Malik-Sheriff, SL Moodie, II Moraru, CJ Myers, A Naldi, BG Olivier, S Sahle, JC Schaff, LP Smith, MJ Swat, DT, L Watanabe, DJ Wilkinson, ML Blinov, K Begley, JR Faeder, HF Gómez, TM Hamm, Y Inagaki, W Liebermeister, AL Lister, D Lucio, E Mjolsness, CJ Proctor, K Raman, N Rodriguez, CA Shaffer, BE Shapiro, J Stelling, N Swainston, N Tanimura, J Wagner, M Meier-Schellersheim, HM Sauro, B Palsson, H Bolouri, H Kitano, Akira Funahashi, H Hermjakob, JC Doyle, M Hucka, SBML Community members

Date Published: 1st Jul 2020

Publication Type: Journal

Robustness and applicability of functional genomic tools on scRNA-seq data
LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network
No description specified

Creator: Christian Holland

Submitter: Christian Holland

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Social media for Academics
LiSyM network

Workshop from LiSyM retreat in January 2020. Additional slides devoted to Social Media for Academics. Developed by Peter Krinenberg from https://naturalscience.careers/

Creator: Olga Vvedenskaya

Submitter: Olga Vvedenskaya

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Pathway modeling with SBML (LiSyM modeling workshop)
Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM network

We face a reproducibility crisis and computational science, with most published models neither being accessible nor reproducible.
The Systems Biology Markup Language (SBML) is the de facto standard format for encoding pathway based models, which provides a means for exchanging process based models between researchers and tools.
The talk gives an overview of SBML and SBML-based tools.

Creator: Matthias König

Submitter: Matthias König

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Participant Abstracts LiSyM Retreat 2020
LiSyM network
No description specified

Creator: Nachiket Vartak

Submitter: Nachiket Vartak

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

Creator: Madlen Matz-Soja

Submitter: Madlen Matz-Soja

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21st International Conference on Systems Biology (ICSB) - POSTPONED to 2021

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: 9th Oct 2021

End Date: 14th Oct 2021

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

Country:  United States

City: Hartford, Connecticut

Systems Biology of Mammalian Cells 2020 (SBMC) - postponed to May 2021

SBMC 2020 was postponed to 10th - 12th of May 2021. Further information will follow soon.

Start Date: 10th May 2021

End Date: 12th May 2021

Event Website: https://sbmc2020.bioquant.uni-heidelberg.de

Country:  Germany

City: Heidelberg

COMBINE 2020 (Computational Modeling in Biology Network Meeting) - VIRTUAL 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:  United States

City: virtual

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/HARMONY_2020

Country:  United Kingdom

City: Hinxton, Cambridge

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:  Germany

City: Bonn

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Poster - Identifying alterations of proliferation signaling in chronic liver disease
LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network

Poster for the PhD retreat in Hofgeismar - Svenja Kemmer

Creator: Svenja Kemmer

Submitter: Svenja Kemmer

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