Matthias König

Matthias König
  • Phd Biophysics
  • Group Leader at Humboldt-Universität zu Berlin

About

105
Publications
31,916
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2,726
Citations
Introduction
The König lab uses Systems Medicine and Systems Biology to study drug metabolism and liver function. We apply computational modeling, data science, data management, bioinformatics analysis and machine learning on biological, medical and clinical data. The main research topics are (i) predictive modeling of biomedical systems with a special focus on the liver, (ii) development of digital twins using physiologically based pharmacokinetic (PBPK) models, (iii) reproducible and open research.
Current institution
Humboldt-Universität zu Berlin
Current position
  • Group Leader
Additional affiliations
January 2016 - present
Humboldt-Universität zu Berlin
Position
  • Junior Group Leader
January 2011 - December 2015
Charité Universitätsmedizin Berlin
Position
  • PhD
January 2010 - present
Education
September 2002 - December 2009
Humboldt-Universität zu Berlin
Field of study
  • Biophysics

Publications

Publications (105)
Preprint
Full-text available
Computational models are essential for studying complex systems which, particularly in clinical settings, need to be quality-approved and transparent. To enhance the communication of a model's features and capabilities, we propose an adaptation of the Findability, Accessibility, Interoperability and Reusability (FAIR) indicators published by the Re...
Preprint
Full-text available
Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of 'da...
Article
Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of 'da...
Preprint
Full-text available
Genome-scale metabolic models (GEMs) and other constraint-based models (CBMs) play a pivotal role in understanding biological phenotypes and advancing research in areas like metabolic engineering, human disease modelling, drug discovery, and personalized medicine. Despite their growing application, a significant challenge remains in ensuring the re...
Preprint
Full-text available
Reproducibility is a foundational standard for validating scientific claims in computational research. Stochastic computational models are employed across diverse fields such as systems biology, financial modelling and environmental sciences. Existing infrastructure and software tools support various aspects of reproducible model development, appli...
Article
Full-text available
There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, ra...
Article
Full-text available
Motivation Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such informa...
Article
Full-text available
Modern biological research is increasingly informed by computational simulation experiments, which necessitate the development of methods for annotating, archiving, sharing, and reproducing the conducted experiments. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Informati...
Preprint
Multiscale modeling requires the coupling of models on different scales, often based on different mathematical approaches and developed by different research teams. This poses many challenges, such as defining interfaces for coupling, reproducible exchange of submodels, efficient simulation of the models, or reproducibility of results. Here, we pre...
Article
Full-text available
Metabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g., metabolic dysfunction-associated steatotic liver disease/MASLD). Zonated metabolic functions are influence...
Article
The SIMulation supported LIVer Assessment for donor organs (SimLivA) project aims to develop a mathematical model to accurately simulate the influence of mechanical alterations in marginal liver grafts (specifically steatotic ones) and cold ischemia on early ischemia‐reperfusion injury (IRI) during liver transplantation. Our project tackles signifi...
Preprint
Full-text available
This study explores the critical interplay between lobular geometry and the zonated distribution of cytochrome P450 (CYP) enzymes across species. We present an innovative approach to assess lobular geometry and zonation patterns using whole slide imaging (WSI). This method allows a detailed, systematic comparison of lobular structures and spatial d...
Article
Full-text available
Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages...
Preprint
Talinolol is a cardioselective beta-blocker used in the treatment of various cardiovascular diseases and tachyarrhythmias. Its intestinal absorption is determined by uptake by the organic anion transporting polypeptide 2B1 (OATP2B1) and efflux via P-glycoprotein (P-gp). Talinolol can be taken up via OATP1B1 in the liver, where it enters the enteroh...
Preprint
Full-text available
Metabolic zonation refers to the spatial separation of metabolic functions along thesinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepaticmetabolism to physiological requirements in health and disease (e.g. metabolicdysfunction-associated steatotic liver disease/ MASLD). Zonated metabolic functions areinfluenced by...
Article
Full-text available
The pancreas plays a critical role in maintaining glucose homeostasis through the secretion of hormones from the islets of Langerhans. Glucose-stimulated insulin secretion (GSIS) by the pancreatic β-cell is the main mechanism for reducing elevated plasma glucose. Here we present a systematic modeling workflow for the development of kinetic pathway...
Preprint
Full-text available
Across disciplines, researchers increasingly recognize that open science and reproducible research practices may accelerate scientific progress by allowing others to reuse research outputs and by promoting rigorous research that is more likely to yield trustworthy results. While initiatives, training programs, and funder policies encourage research...
Preprint
The cytochrome P450 (CYP) superfamily of enzymes plays a critical role in the metabolism of drugs, toxins, and endogenous and exogenous compounds. The activity of CYP enzymes can be influenced by a variety of factors, including genetics, diet, age, environmental factors, and disease. Among the major isoforms, CYP2E1 is of particular interest due to...
Article
Full-text available
This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2022 special issue presents three updates to the standards: CellML 2.0.1, SBML Level 3 Package: Spatial Processes, Version 1, Release 1, and Synthetic Biology Open Language (SBOL) Version 3.1.0....
Preprint
Full-text available
The field of metabolic modelling at the genomescale continues to grow with more models being created and curated. This comes with an increasing demand for adopting common principles regarding transparency and versioning, in addition to standardisation efforts regarding file formats, annotation and testing. Here, we present a standardised template f...
Preprint
Full-text available
The pancreas plays a critical role in maintaining glucose homeostasis through the secretion of hormones from the islets of Langerhans. Glucose-stimulated insulin secretion (GSIS) by the pancreatic beta-cell is the main mechanism for reducing elevated plasma glucose. Here we present a systematic modeling workflow for the development of kinetic pathw...
Preprint
Hypercholesterolemia is a multifaceted plasma lipid disorder with heterogeneous causes including lifestyle and genetic factors. A key feature of hypercholesterolemia is elevated plasma levels of low-density lipoprotein cholesterol (LDL-C). Several genetic variants have been reported to be associated with hypercholesterolemia, known as familial hype...
Article
Full-text available
The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) est...
Article
Full-text available
Little is known about the impact of morphological disorders in distinct zones on metabolic zonation. It was described recently that periportal fibrosis did affect the expression of CYP proteins, a set of pericentrally located drug-metabolizing enzymes. Here, we investigated whether periportal steatosis might have a similar effect. Periportal steato...
Article
Full-text available
Motivation This paper presents libRoadRunner 2.0, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using the Systems Biology Markup Language (SBML). Results libRoadRunner is a self-contained library, able to run either as a component inside other tools via its C ++, C...
Article
Full-text available
The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) est...
Preprint
The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) est...
Preprint
A major challenge for the dissemination, replication, and reuse of epidemiological forecasting studies during COVID-19 pandemics is the lack of clear guidelines and platforms to exchange models in a Findable, Accessible, Interoperable, and Reusable (FAIR) manner, facilitating reproducibility of research outcomes. During the beginning of pandemics,...
Article
Full-text available
Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed throug...
Article
Full-text available
Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and theophylline. Besides its stimulati...
Preprint
Full-text available
Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed throug...
Article
Full-text available
Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and theophylline. Besides its stimulati...
Preprint
Motivation: This paper presents libRoadRunner 2.0, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using Systems Biology Markup Language SBML). Results: libRoadRunner is a self-contained library, able to run both as a component inside other tools via its C++ and C bin...
Article
Full-text available
Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery....
Article
Full-text available
The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology as well as in hepatobiliary surgery. Indocyanine green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of hepatecto...
Article
Full-text available
Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties an...
Preprint
Full-text available
Science continues to become more interdisciplinary and to involve increasingly complex data sets. Many projects in the biomedical and health-related sciences follow or aim to follow the principles of FAIR data sharing, which has been demonstrated to foster collaboration, to lead to better research outcomes, and to help ensure reproducibility of res...
Article
Full-text available
This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2021 special issue presents four updates of standards: Synthetic Biology Open Language Visual Version 2.3, Synthetic Biology Open Language Visual Version 3.0, Simulation Experiment Description Ma...
Article
Full-text available
A standardized approach to annotating computational biomedical models and their associated files can facilitate model reuse and reproducibility among research groups, enhance search and retrieval of models and data, and enable semantic comparisons between models. Motivated by these potential benefits and guided by consensus across the COmputational...
Article
Full-text available
In systems biology, biological phenomena are often modeled by Ordinary Differential Equations (ODEs) and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for...
Article
Full-text available
Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulat...
Article
Full-text available
Studying biological systems generally relies on computational modelling and simulation, e.g., model-driven discovery and hypothesis testing. Progress in standardisation efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED...
Preprint
Science continues to become more interdisciplinary and to involve increasingly complex data sets. Many projects in the biomedical and health related sciences adhere to the principles of FAIR data sharing, or aim to follow them. Data sharing has been proven to foster collaboration, to lead to better research outcomes, and to help ensure reproducibil...
Preprint
Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery....
Preprint
In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published....
Preprint
Full-text available
Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages. Caffeine is almost completely metabolized in the liver by the cytochrome P-450 enzyme system mainly to paraxanthine and the additional products theobromine and theophylline. Besides its stimulating properties, two i...
Preprint
Full-text available
The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology, especially in the context of liver surgery. Indocyanine Green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of h...
Preprint
Full-text available
More sophisticated models are needed to address problems in bioscience, synthetic biology, and precision medicine. To help facilitate the collaboration needed for such models, the community developed the Simulation Experiment Description Markup Language (SED-ML), a common format for describing simulations. However, the utility of SED-ML has been ha...
Preprint
Studying biological systems generally relies on computational modeling and simulation, e.g., for model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (...
Article
Full-text available
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://pk-db.com), an open database for pharmacokinetics information from clinical trials. PK-DB provides curated informati...
Article
Full-text available
Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community...
Article
Full-text available
Biological models often contain elements that have inexact numerical values, since they are based on values that are stochastic in nature or data that contains uncertainty. The Systems Biology Markup Language (SBML) Level 3 Core specification does not include an explicit mechanism to include inexact or stochastic values in a model, but it does prov...
Article
Full-text available
This special issue of the Journal of Integrative Bioinformatics presents papers related to the 10th COMBINE meeting together with the annual update of COMBINE standards in systems and synthetic biology.
Article
Full-text available
This paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic...
Article
Full-text available
A standardized approach to annotating computational biomedical models and their associated files can facilitate model reuse and reproducibility among research groups, enhance search and retrieval of models and data, and enable semantic comparisons between models. Motivated by these potential benefits and guided by consensus across the COmputational...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preprint
To address the issue of reproducibility in computational modeling we developed the concept of an executable simulation model (EXSIMO). An EXSIMO combines model, data and code with the execution environment to run the computational analysis in an automated manner using tools from software engineering. Key components are i) models, data and code for...
Chapter
To address the issue of reproducibility in computational modeling we developed the concept of an executable simulation model (EXSIMO). An EXSIMO combines model, data and code with the execution environment to run the computational analysis in an automated manner using tools from software engineering. Key components are (i) models, data and code for...
Preprint
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://pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research....
Article
Full-text available
Numerical modeling of biological systems has become an important assistance for understanding and predicting hepatic diseases like non‐alcoholic fatty liver disease (NAFLD) or the detoxification of drugs and toxines by the liver. We developed a model for the simulation of hepatic function‐perfusion processes using a multiscale and multiphase approa...
Article
Full-text available
This special issue of the Journal of Integrative Bioinformatics presents an overview of COMBINE standards and their latest specifications. The standards cover representation formats for computational modeling in synthetic and systems biology and include BioPAX, CellML, NeuroML, SBML, SBGN, SBOL and SED-ML. The articles in this issue contain updated...
Article
Full-text available
Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The S ystems B iology M arkup L anguage (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological proc...
Article
Full-text available
Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-re...
Article
Full-text available
Here we present Tellurium, a Python-based environment for model building, simulation, and analysis that facilitates reproducibility of models in systems and synthetic biology. Tellurium is a modular, cross-platform, and open-source simulation environment composed of multiple libraries, plugins, and specialized modules and methods. Tellurium is a se...
Article
Full-text available
The considerable difficulty encountered in reproducing the results of published dynamical models limits validation, exploration and reuse of this increasingly large biomedical research resource. To address this problem, we have developed Tellurium Notebook, a software system for model authoring, simulation, and teaching that facilitates building re...
Data
A normative example of a COMBINE archive introduced in the original paper describing the COMBINE archive format [26]. This example contains the repressilator model [92], a damped oscillation variant showing the modification of model parameters using SED–ML, and a phase portrait of the undamped system. (EPS)
Data
Round-tripping the SED–ML Web Tools examples [27]. In order to demonstrate broad support for standards, we conducted a series of tests utilizing advanced usage of SED–ML. The first row shows the original example rendered in the SED–ML Web Tools. The second row shows the same example imported into Tellurium. The third row shows the simulation after...
Data
Tellurium SBML test suite results. This table shows the results of converting the SBML test suite into COMBINE archives and running the test cases with Tellurium. Notebooks for running these tests and converting the SBML test suite to COMBINE archives can be found in our repository [96]. The SBML test suite was converted into COMBINE archives using...
Data
Combine archive test cases. We collected all COMBINE archives used during development of Tellurium in an online repository on GitHub [93]. These archives serve to test Tellurium’s standards compliance, but they may also allow other tool developers to better support COMBINE archives. We have therefore organized the test cases into different categori...
Data
Advanced SED–ML tests (provided by the SED–ML Web Tools [27]). The SBML test suite was converted into COMBINE archives using the provided notebook https://github.com/0u812/tellurium-combine-archive-test-cases/blob/master/sbml-test-suite/convert-to-combine-arch.ipynb. These SBML test cases are automatically converted into COMBINE archives containing...
Data
Demonstrating exchangeability of the second case study. To show that the extended set of simulations from Fig 4 can be exchanged with other tools via a COMBINE archive, we exported the study in Fig 4 to the SED–ML Web Tools and verified that the plots were identical to Fig 4. (EPS)
Data
Examples of Tellurium’s inline OMEX format for specifying COMBINE archives. These examples start with very simple cases and build on these cases with progressively more advanced features. The first example contains a simple two–species model and simulated using a deterministic and stochastic solver. The second example shows a phase portrait. The th...
Article
Full-text available
The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-M...
Preprint
Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-re...
Preprint
Motivation Systems biology models are typically simulated using a single formalism such as ordinary differential equations (ODE) or stochastic methods. However, more complex models require the coupling of multiple formalisms since different biological concepts are better described using different methods, e.g., stationary metabolism is often modele...
Preprint
Full-text available
The considerable difficulty encountered in reproducing the results of published dynamical models limits validation, exploration and reuse of this increasingly large biomedical research resource. To address this problem, we have developed Tellurium Notebook, a software system that facilitates building reproducible dynamical models and reusing models...
Article
Full-text available
The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver re...
Article
Full-text available
Kinetic data of biochemical reactions are essential for the creation of kinetic models of biochemical networks. One of the main resources of such information is SABIO-RK, a curated database for kinetic data of biochemical reactions and their related information. Despite the importance for computational modelling there has been no simple solution to...
Preprint
Full-text available
Kinetic data of biochemical reactions are essential for the creation of kinetic models of biochemical networks. One of the main resources of such information is SABIO-RK, a curated database for kinetic data of biochemical reactions and their related information. Despite the importance for computational modelling there has been no simple solution to...
Article
Full-text available
Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose sev...
Article
In this article, we present Tellurium, a powerful Python-based integrated environment designed for model building, analysis, simulation and reproducibility in systems and synthetic biology. Tellurium is a modular, cross-platform, and open-source integrated development environment (IDE) composed of multiple libraries, plugins, and specialized module...
Preprint
Full-text available
In this article, we present Tellurium, a powerful Python-based integrated environment designed for model building, analysis, simulation and reproducibility in systems and synthetic biology. Tellurium is a modular, cross-platform, and open-source integrated development environment (IDE) composed of multiple libraries, plugins, and specialized module...
Article
Full-text available
Disrupted bile secretion leads to liver damage characterized by inflammation, fibrosis, eventually cirrhosis, and hepatocellular cancer. As obstructive cholestasis often progresses insidiously, markers for the diagnosis and staging of the disease are urgently needed. To this end, we compiled a comprehensive data set of serum markers, histological p...
Article
Biochemical reactions in the liver are a complex non-linear and time depending coupled function-perfusion-mechanisms. The metabolism of the liver, e.g. nutrient storage, is directly coupled to its blood perfusion. Growth phenomena, such as accumulation of fat, have a strong impact onto micro-perfusion within the liver. Here, we present the results...
Article
Full-text available
Motivation: This article presents libRoadRunner, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using Systems Biology Markup Language (SBML). SBML is the most widely used standard for representing dynamic networks, especially biochemical networks. libRoadRunner is f...
Article
Fatty liver is a common disease in the western society. Different stimuli, such as obesity or abuse of alcohol, cause the liver to store fat within liver cells, the so called hepatocytes. This growth induced by storage of fat influences the perfusion of the overlying structures, i. e. sinusoids, liver lobules, liver lobes, and consequently the live...
Article
Full-text available
This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as...
Article
Characteristics of many tumor types are the reprogramming of metabolism and the occurrence of regional hypoxia. In this work we investigated the hypothesis that metabolic reprogramming in combination with metabolic zonation of cellular energy metabolism are important factors to promote the growth capacity of solid tumors. A tissue-scale model of th...
Article
Full-text available
A major problem in the insulin therapy of patients with diabetes type 2 (T2DM) is the increased occurrence of hypoglycemic events which, if left untreated, may cause confusion or fainting and in severe cases seizures, coma and even death. To elucidate the potential contribution of the liver to hypoglycemia in T2DM we applied a detailed kinetic mode...

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