Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF)

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

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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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 ...

Collection of Presentations and Posters from Dresden LiSyM Jamboree (LiFuDi & MM-PLF)

Pillar IV Jamboree • (10 min) Introduction to Pillar IV (Hergo Holzhütter) • (20 min) Precise Measurement of Hepatic Elasticity for Fibrosis Detection (Christian Hudert) • (20 min) Tissue Scale Metabolic Modelling (Sascha Bulik) • (10 min) Multi-scale models for liver function tests (Matthias König) • (20 min) Improving the diagnostic precision of the 13C-methacetin dynamic liver function test (LiMAx) (Tilo ...

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) ...

Pharmacokinetics data set for caffeine

Data digitized from publication.

Hetzler1990 Description

Data digitized from publication.

Spigset1999a Description

Data digitized from publication.

Akinyinka2000 Description

Data digitized from publication.

Perera2011 Description

Data digitized from publication.

Amchin1999 Description

Digitized pharmacokinetics data.

Digitized pharmacokinetics data.

Digitized pharmacokinetics data.

Digitized pharmacokinetics data.

Digitized pharmacokinetics data.

PK-DB: PharmacoKinetics DataBase for Individualized and Stratified Computational Modeling Jan Grzegorzewski, Janosch Brandhorst, Dimitra Eleftheriadou, Kathleen Green, Matthias König bioRxiv 760884; doi: https://doi.org/10.1101/760884

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.

Assessment of liver function is a key task in hepatology but accurate quantification of hepatic function has remained a clinical challenge. Dynamic liver function tests are a promising tool for the non-invasive evaluation of liver function in vivo. Quantitative dynamical liver function tests evaluate the function of the liver via the clearance of a given test substance, thereby providing in vivo information on the metabolic capacity of the liver. Here, we present recent results in establishing ...

Improved evaluation of caffeine-based dynamical liver function tests by accounting for lifestyle and pharmacological modifiers like smoking and oral contraceptive use

Matthias König1,*, Ute Hofmann2, Jan Grzegorzewski1, Reinhold Kerb2, Svitlana Igel2, Elke Schäffeler2 and Matthias Schwab2,3

1Institute for Theoretical Biology, Institute of Biology, Humboldt University, Berlin, Germany, koenigmx@hu-berlin.de, orcid.org/0000-0003-1725-179X 2Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, ...

In the growing elderly societies, the incidence of primary and secondary liver tumors is continuously increasing. Surgical interventions like partial liver resections are often the only curative therapy removing more than 70% of the total liver mass. In humans, 20% to 30% of the remaining liver is required for liver regeneration. Successful restoration of the liver mass ultimately depends on the regenerative and metabolic capacity of the hepatocytes in the remnant liver. This, however, might be ...

Modeling tutorial as part of the 1st LiSyM Retreat Meeting in Hünfeld (20-22 November 2017).

This tutorial gives a quick introduction into standards used in computational modeling and visualizes, simulates and analysis showcase example models. A basic introduction to simple kinetic models is provided.

The latest material is available from https://github.com/matthiaskoenig/lisym-tutorial under https://github.com/matthiaskoenig/lisym-tutorial/releases. The presentation is available from the within ...

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.

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, ...

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

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.