LiSyM: Liver Systems Medicine

Dr. Madlen Matz-Soja (University of Leipzig) investigates the importance of a control mechanism - the hedgehog signaling pathway - for fatty liver disease. She has shown that the signaling pathway directs how liver cells in NAFLD accumulate fat. Hedgehog also affects sex hormones in the liver. Therefore, Matz-Soya hopes to clarify why women and men suffer from cirrhosis and liver cancer with varying degrees of frequency.

In one in five people with NAFLD, the functioning liver cells, the hepatocytes, are replaced by connective tissue. Eventually this fibrosis becomes irreversible. In this state the liver is like a ‘scar that never heals’. Through it, the liver loses many of its vital functions.
LiSyM-Pillar II wants to know more about which factors promote fibrosis and the conditions under which fibrosis becomes irreversible How can fibrosis be diagnosed as early as possible? Researchers in the pillar are also
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This comprises the whole LiSyM network

Disorders of the liver show up through changes in blood tests. These blood tests indicate markers for events taking place in the liver. Usually studies of liver tissue cannot be performed: as liver samples would need to be obtained through a liver biopsy, and this procedure is not without risk, therefore these samples are usually unavailable. Complex metabolism models based on existing and new scientific data can simulate changes in the liver caused by disease. They often reveal unknown relationships
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Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction

Liver macrophages (LMs) play a central role in acute and chronic liver pathologies. In our study, we sought to gain further insight into the role of LMs in different liver pathologies and into their characteristics after isolation from liver tissue. Here we will characterize LMs in human liver tissue sections using immunohistochemistry and bioinformatic image analysis.
We investigate liver tissues characterized by antiinflammatory LMs which show a homogeneous distribution and increased cell numbers
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We face a crisis in reproducibility, where it is impossible to believe most of the computational results shown in conferences and papers. Recent replication efforts and theoretical considerations indicate that most published research findings in biomedical research are wrong. This is especially problematic for the translation of computational models into the clinics. Modelling standards, software, and community initiatives are fundamental for reproducibility in systems biology and systems medicine.
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Test for SEEK API upload.

Introduction: The field of pharmacokinetics describe the kinetics of substances administered to the body, consisting of absorption, distribution, metabolization and elimination (ADME) of the substance. An important use case is the testing of liver function via test substances like caffeine, methacetin or galactose in dynamical liver function tests. Understanding the kinetics of test substances and drugs is crucial to
evaluate therapeutic outcome and diagnostic value.

Results: Physiologically based
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A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://develop.pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status); (ii)
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Pharmacokinetics data set for caffeine

Data digitized from publication.

Jeppesen1996 Description

Data digitized from publication.

Magnusson2008 Description

Data digitized from publication.

Kaplan1997 Description

Data digitized from publication.

Tanaka2014 Description

This asset is going to be changed later. Its purpose is providing an accessible URL that stays.

The model is adapted from A.P. Kupinski, I. Raabe, M. Michel, D. Ail, L. Brusch, T. Weidemann, C. Bökel (2013) Phosphorylation of the Smo tail is controlled by membrane localization and is dispensable for clustering, J. Cell Sci., 126, 20, 4684-4697 https://doi.org/10.1242/jcs.128926

The model format is MorpheusML that can readily be loaded and run in Morpheus: https://morpheus.gitlab.io

Model for the interaction of Wnt and Hh as published in Kolbe et al.: Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human, Cell Reports, 29,4553,

https://doi.org/10.1016/j.celrep.2019.11.104

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
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Morpheus is the modelling and simulation framework for multicellular systems biology developed at Technische Universität Dresden.
Manual, examples and binaries for Windows, Linux, MacOS at: https://morpheus.gitlab.io
Open source code at: https://gitlab.com/morpheus.lab/morpheus

Code for the bile flow model in Segovia-Miranda et al.: Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression (https://www.nature.com/articles/s41591-019-0660-7)

See the README file in the link for details installing and running the code.

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

Macrophage staining in paraffin-embedded tissue

This SOP - Standard Operating Procedure for Sample Collection and Preservation of Blood and
Endometrial Tissue were developed at NIH University of California San Francisco Human Endometrial Tissue and DNA Bank
by Elizabeth Sheldonand, Ramsey A McIntire

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.

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

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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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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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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Poster for the PhD retreat in Hofgeismar - Svenja Kemmer

Small movie explaining how to associate authors to profiles.