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Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Overview

Chronic liver diseases (CLD) progression leads to cirrhosis, often cancer, and ultimately to organ failure and death. Because of the complexity of this scenario, a Systems Medicine approach is chosen to develop strategies to better characterize progression and resolution of fibrosis. Pillar II aims to define key molecular mechanisms and structural changes in tissue architecture during the progression of CLD by visualizing and quantifying at a cellular level, tissue and organ scale.

SEEK ID: https://seek.lisym.org/projects/4

Public web page: Not specified

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus

FAIRDOM PALs: Janine Koehncke, Annika Schneider, Daniel Lill, Seddik Hammad, Matthias Reichert

Project created: 21st Feb 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

Marie-Luise Berres

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

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

Johannes Bode

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

Institutions: Universitätsklinikum Düsseldorf - Klinik für Gastroenterologie, Hepatologie und Infektiologie

Lorenza D'Alessandro

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

Institutions: Deutsches Krebsforschungszentrum

Jules Dichamp

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

Institutions: INRIA (French National Institute for Research in Computer Science and Control), Leibniz-Institut für Arbeitsforschung (IfADo)

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

Pillar II dooley

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CCl4 Treatment in mice
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Person responsible: Seddik Hammad

Snapshots: No snapshots

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Metabolic CCl4
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Contributor: Seddik Hammad

Assay type: Proteomics

Technology type: FACS

Snapshots: No snapshots

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

GitHub repository containing the analysis code

Creator: Christian Holland

Contributor: Christian Holland

External Link
Transfer of regulatory knowledge from human to mouse for functional genomics analysis
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

GitHub repository that contains all analyses scripts to reproduce the results reported in "Transfer of regulatory knowledge from human to mouse for functional genomics analysis"

Creator: Christian Holland

Contributor: Christian Holland

Movies for quantification
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
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Creator: Seddik Hammad

Contributor: Seddik Hammad

TextBookData
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
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Creators: None

Contributor: Seddik Hammad

F4-80
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
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Creators: None

Contributor: Seddik Hammad

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SOP RNA Isolation from healthy and fatty liver
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)
No description specified

Creator: Sonja Kleeschulte

Contributor: Sonja Kleeschulte

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SOP FACS analysis of Macrophage population in healthy and fatty liver
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)

Non-parenchymal liver cells are isolated and staining for FACS analysis

Creator: Sonja Kleeschulte

Contributor: Sonja Kleeschulte

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SOP Immunhistochemistry Mac2 staining
Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)

Macrophage staining in paraffin-embedded tissue

Creator: Sonja Kleeschulte

Contributor: Sonja Kleeschulte

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

Journal: Genome Biol

Transfer of regulatory knowledge from human to mouse for functional genomics analysis
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 analyze and interpret. Functional genomics 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 (2374). 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: 1st Sep 2019

Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

TGF-β2 silencing to target biliary-derived liver diseases
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Abstract

Not specified

Authors: Anne Dropmann, Steven Dooley, Bedair Dewidar, Seddik Hammad, Tatjana Dediulia, Julia Werle, Vanessa Hartwig, Shahrouz Ghafoory, Stefan Woelfl, Hanna Korhonen, Michel Janicot, Katja Wosikowski, Timo Itzel, Andreas Teufel, Detlef Schuppan, Ana Stojanovic, Adelheid Cerwenka, Stefanie Nittka, Albrecht Piiper, Timo Gaiser, Naiara Beraza, Malgorzata Milkiewicz, Piotr Milkiewicz, John G Brain, David E J Jones, Thomas S Weiss, Ulrich M Zanger, Matthias Ebert, Nadja M Meindl-Beinker

Date Published: 28th Jan 2020

Journal: Gut

Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin.
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Abstract (Expand)

PURPOSE: Evaluation of [(68)Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity … of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [(68)Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [(68)Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [(68)Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [(68)Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Authors: A. Rix, N. I. Drude, Anna Mrugalla, F. Baskaya, K. Y. Pak, B. Gray, H. J. Kaiser, R. H. Tolba, E. Fiegle, Wiltrud Lederle, F. M. Mottaghy, F. Kiessling

Date Published: 8th Aug 2019

Journal: Mol Imaging Biol

Adenovirusmediated overexpression of bone morphogenetic protein9 promotes methionine choline deficiencyinduced nonalcoholic steatohepatitis in nonobese mice.
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

Abstract (Expand)

Liver inflammation and macrophage infiltration are critical steps in the progression of nonalcoholic fatty liver to the development of nonalcoholic steatohepatitis. Bone morphogenetic protein9 is a … cytokine involved in the regulation of chemokines and lipogenesis. However, the function of bone morphogenetic protein9 in nonalcoholic steatohepatitis is still unknown. The present study hypothesized that bone morphogenetic protein9 may contribute to steatohepatitis in mice fed a methionine choline deficiency diet (MCD). C57BL/6 mice overexpressing bone morphogenetic protein9 and control mice were fed the MCD diet for 4 weeks. Liver tissue and serum samples were obtained for subsequent measurements. Bone morphogenetic protein9 overexpression exacerbated steatohepatitis in mice on the MCD diet, as indicated by liver histopathology, increased serum alanine aminotransferase activity, aspartate transaminase activity, hepatic inflammatory gene expression and M1 macrophage recruitment. Although bone morphogenetic protein9 overexpression did not affect the expression of profibrogenic genes, including Collagen I (alpha)1 or matrix metalloproteinase (MMP) 9, it did upregulate the expression of transforming growth factorbeta and plasminogen activator inhibitor 1, and downregulated the expression of MMP2. The above results indicate that bone morphogenetic protein9 exerts a proinflammatory role in MCD dietinduced nonalcoholic steatohepatitis.

Authors: Q. Li, B. Liu, K. Breitkopf-Heinlein, H. Weng, Yixin Jiang, P. Dong, Steven Dooley, K. Xu, H. Ding

Date Published: 20th Jul 2019

Journal: Mol Med Rep

CYP2E1 recovery is associated with a pericentral fibrosis pattern after repeated CCl4 insults
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

Cellular and nuclear hepatocyte ploidy represent a repository in regenerating livers
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

Decreased ECM1 expression is consistent in HCC and correlates with overall survival
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

GPNMB as hepatocytic suppressor of steatosis and liver cancer
Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
No description specified

Creator: Seddik Hammad

Contributor: Seddik Hammad

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

Creator: Christian Holland

Contributor: Christian Holland

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First LiSyM PostDoc and PhD student retreat

The meeting will provide a great opportunity for discussion between modellers, experimentalists and clinicians and to organize and harmonize our future work within the LiSyM network on the grassroot level.

Start Date: 20th Nov 2017

End Date: 22nd Nov 2017

Event Website: Not specified

Country:  Germany

City: Hünfeld

International Conference on Systems Biology of Human Disease (SBHD)

The International Conference on Systems Biology of Human Disease (SBHD) is a transatlantic event and communication platform for scientific exchange that takes place alternately between the United States and Germany.

SBHD 2017 is continuing a conference series launched by Peter Sorger and colleagues from Harvard Medical School in 2008. The conference focus is on mammalian systems biology, particularly on its application to human disease and therapy.

Start Date: 5th Jul 2017

End Date: 7th Jul 2017

Event Website: http://www.sbhd-conference.org/2017/index.php

Country:  Germany

City: Heidelberg

First EASL Nonalcoholic Fatty Liver Disease (NAFLD) Summit: Target-oriented approach to Diagnosis and Pharmacotherapy of Nonalcoholic Steatohepatitis (NASH), a dialogue between Academia and Industry

This summit will cover both the basic and translational / clinical aspects of NAFLD, with a specific focus on novel drug target and prognostic signature development.

Key sessions include all crucial pathophysiological aspects currently known to affect development and progression of NAFLD, such as "lipid metabolism and lipotoxicity" and "insulin resistance, insulin and hormonal signaling". Furthermore, oxidative stress, ER stress, and mitochondrial dysfunction will be addressed. On the second day,
...

Start Date: 9th Nov 2017

End Date: 11th Nov 2017

Event Website: https://events.easl.eu/EventPortal/Information/EventInformation.aspx?EventInformationPageCode=HOME&EventCode=nafld2017

Country:  Italy

City: Rome

18th International Conference on Systems Biology (ICSB 2017)

ICSB continues to be the flagship conference of the International Society for Systems Biology (ISSB). The conference will cover a variety of themes from Fundamental Biological Sciences, Network Analysis, to Metabolic Engineering and Cancer Biology. The conference will also include a variety of engaging plenary lectures, parallel sessions, poster sessions, and interactive networking opportunities.

Abstract submission deadline: May 13th, 2017

Start Date: 6th Aug 2017

End Date: 12th Aug 2017

Event Website: http://www.cpe.vt.edu/icsb2017/

Country:  United States

City: Blacksburg, Virginia

Joint LiSyM & ERASysAPP Data Management PALs Meeting

This event is a jointly organized Data Management PALs Meeting that involves PALs from the German LiSyM (Liver Systems Medicine) network and from the ERASysAPP (ERA-Net for Systems Biology Applications) initiative. PALs (Project Area Liaisons) are the front line experts of the data management teams of these projects. They act as data management advocates and help gathering user requirements and testing potential data management solutions. An important part of the meeting will be to gather the
...

Start Date: 2nd May 2017

End Date: 3rd May 2017

Event Website: https://fairdomhub.org/events/64

Country:  Germany

City: 36088 Hünfeld bei Fulda

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