Systems Medicine & Biology for Advanced Drug Metabolism and Liver Studies

At the König Lab, we merge the fields of Systems Medicine and Systems Biology to delve deep into drug metabolism and liver function. By harnessing the power of computational modeling, data science, bioinformatics analysis, and machine learning, we analyze and interpret datasets spanning biological, medical, and clinical spheres.

Interested in joining the lab, have a look at the open positions.

Our Core Research Avenues

  • Predictive Biomedical Modeling: With a primary emphasis on the liver and kidneys, we strive to foresee how these systems react and interact.
  • Digital Twins Development: We pioneer in creating digital replicas using physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models.
  • Reproducibility and Open Research: We champion transparent methodologies and workflows, ensuring our work can be revisited and built upon.
  • FAIR Data & Workflows: Ensuring that our data and workflows are Findable, Accessible, Interoperable, and Reusable is pivotal to our mission.

Flagship Projects

  • Personalized assessments of liver and kidney functions.
  • Multi-scale modeling endeavors for the liver.
  • Advanced pharmacometric strategies.
  • Crafting databases and workflows that serve as cornerstones for reproducible, open, and FAIR research.

A hallmark of our research is the generation of predictive digital twins mirroring individual human physiology. These models are instrumental in shedding light on inter-individual variances, paving the way for personalized treatments—from tailoring drug dosages to understanding the nuanced impacts of lifestyle on drug metabolism. For more information, please see our publications and projects.

Contact

Group Leader
Dr. Matthias König


Systems Medicine of the Liver
Institute for Biology, Institute for Theoretical Biology
Humboldt Universität zu Berlin
Philippstraße 13, 10115 Berlin, Germany
+49 30 2093-98435
koenigmx@hu-berlin.de

Funding

For more information, see our funding.

           

Editor

We are actively involved in the standardization and reproducibility efforts in Systems Biology and Systems Medicine.
2020-2023 COMBINE coordinator
The COmputational Modeling in BIology NEtwork (COMBINE) is an initiative to coordinate the development of the various community standards and formats for computational models.
2023-2026 PETab editor
PEtab is a data format for specifying parameter estimation problems in systems biology.
2018-2023 SBML editor
The Systems Biology Markup Language (SBML) is a software data format for describing models in biology.
2017-2022 SED-ML editor
The Simulation Experiment Description Markup Language (SED-ML) is a format for encoding simulation setups, to ensure exchangeability and reproducibility of simulation experiments.

Software

We are actively involved in the standardization and reproducibility efforts in Systems Biology and Systems Medicine. For more information, see our software.
PK-DB - Pharmacokinetics database
An open database for pharmacokinetics information from clinical trials as well as pre-clinical research.
sbmlutils - Python utilities for SBML
sbmlutils is a collection of python utilities for working with SBML models implemented on top of libsbml and other libraries.
SBML4Humans - SBML simulation made easy
The objective of SBML4Humans is to provide an interactive and reactive report for SBML models which allows humans (experts as well as beginners) to easily comprehend the content of a model.
sbmlsim - SBML simulation made easy
sbmlsim is a collection of python utilities to simplify simulations with SBML models implemented on top of roadrunner.
cysbml - Cytoscape 3 app for the Systems Biology Markup Language
cy3sbml is a Cytoscape 3 app for the Systems Biology Markup Language SBML. Our mission is the visualization of SBML information within the network context.
brendapy - BRENDA in python
The brendapy package provides a python parser and utility functions for enzyme information from BRENDA.
libsbgnpy - Python library for SBGN
Python library to work with the Systems Biology Graphical Notation (SBGN).
roadrunner - Contributor to the high-performance simulator for SBML
libRoadRunner is a C/C++ library that supports simulation of SBML based models. It uses LLVM) to generate extremely high performance code.
COBRApy - Contributor to the COBRA python package
COBRApy is a constraint-based modeling package that is designed to accommodate the biological complexity of the next generation of COBRA models and provides access to commonly used COBRA methods, such as flux balance analysis, flux variability analysis, and gene deletion analyses.
cobrapy - Contributor to the tellurium simulator
Tellurium is a python environment for reproducible dynamical modeling of biological networks. Tellurium provides the interfacial code to convert between standard formats and utilize powerful libraries without requiring technical expertise, allowing you to focus on what’s important: building better models.

Teaching

For more information, see our teaching.
Theory, tools and methods in biology HP. Herzel, R. Kempter, S. Schreiber, P. Kuokkanen, R. Steuer, JH. Schleimer, P. Romanczuk, N. Blüthgen, M. König SS23  lecture,  course
X-Student Research Group: Physiologically based digital twins for the treatment of hypertension with ACE inhibitors and diuretics M. König SS23  lecture,  course
Theory, tools and methods in biology HP. Herzel, R. Kempter, S. Schreiber, P. Kuokkanen, R. Steuer, JH. Schleimer, P. Romanczuk, N. Blüthgen, M. König SS23  lecture,  course
X-Student Research Group: Physiologically based modeling of drugs: ACE inhibitors in the treatment of high blood pressure M. König WS22/23  lecture,  course
Important models of quantitative biology from the literature R. Steuer, P. Romanczuk, N. Blüthgen, M. König WS21/22  seminar,  course
Important models of quantitative biology from the literature R. Steuer, P. Romanczuk, N. Blüthgen, M. König WS20/21  seminar,  course
Models of cellular processes M. König, R. Steuer WS19/20  lecture
Important models of quantitative biology from the literature N.Blüthgen, M.König, R.Steuer WS19/20  seminar,  course
Important models of quantitative biology from the literature N. Blüthgen, R.Steuer, M. König WS18/19  seminar,  course

Publications

2024 Cross-Species Variability in Lobular Geometry and Cytochrome P450 Hepatic Zonation: Insights into CYP1A2, CYP2E1, CYP2D6 and CYP3A4
Mohamed Albadry, Jonas Kuettner, Jan Grzegorzewski, Olaf Dirsch, Eva Kindler, Robert Klopfleisch, Vaclav Liska, Vladimira Moulisova, Sandra Nickel, Richard Palek, Jachym Rosendorf, Sylvia Saalfeld, Utz Settmacher, Hans-Michael Tautenhahn, Matthias König*, Uta Dahmen* (* equal contribution)
Front Pharmacol. 2024 May 16;15:1404938. doi:10.3389/fphar.2024.1404938. pmid:38818378
2024 Enhancing Our Understanding of Enalapril’s Pharmacokinetics: A Physiologically Based Modeling Approach
Master Thesis Shubhankar Palwankar (supervisor: Matthias König)
Master Thesis, May 2024
2024 Bayesian modelling of time series data (BayModTS)-a FAIR workflow to process sparse and highly variable data
Höpfl S, Albadry M, Dahmen U, Herrmann KH, Kindler EM, König M, Reichenbach JR, Tautenhahn HM, Wei W, Zhao WT, Radde NE.
Bioinformatics. 2024 May 2;40(5):btae312. doi:10.1093/bioinformatics/btae312. pmid:38741151
2024 Specifications of Standards in Systems and Synthetic Biology: Status, Developments and Tools in 2024
M. Golebiewski, P. Gleeson, T. Gorochowski, M. Hucka, S. Keating, M. König, C. Myers, D. Nickerson, H. Sommer, D. Waltemath, F. Schreiber
J Integr Bioinform. 2024 (accepted)
2024 The simulation experiment description markup language (SED-ML): language specification for level 1 version 5
Smith LP, Bergmann FT, Garny A, Helikar T, Karr J, Nickerson D, Sauro H, Waltemath D, König M.
J Integr Bioinform. 2024 Apr 15. doi:10.1515/jib-2024-0008. pmid:38613325
2024 Simulation of zonation-function relationships in the liver using coupled multiscale models: Application to drug-induced liver injury
Steffen Gerhäusser, Lena Lambers, Luis Mandl, Julian Franquinet, Tim Ricken, Matthias König
bioRxiv 2024.03.26.586870; (preprint). doi:10.1101/2024.03.26.586870
2024 Quantifying fat zonation in liver lobules: an integrated multiscale in silico model combining disturbed microperfusion and fat metabolism via a continuum biomechanical bi-scale, tri-phasic approach
Lena Lambers, Navina Waschinsky, Jana Schleicher, Matthias König, Hans-Michael Tautenhahn, Mohamed Albadry, Uta Dahmen and Tim Ricken
Biomech Model Mechanobiol. 2024 Feb 25.. doi:10.1007/s10237-023-01797-0. pmid:38402347
2024 SimLivA – Modelling ischemia reperfusion injury in the liver: A first step towards a clinical decision support tool.
Hans-Michael Tautenhahn, Tim Ricken, Uta Dahmen, Luis Mandl, Laura Bütow, Steffen Gerhäusser, Lena Lambers, Xinpei Chen, Elina Lehmann, Olaf Dirsch, Matthias König
GAMM-Mitteilungen. (2024), e202370003. doi:10.1002/gamm.202370003
2024 A physiologically-based pharmacokinetic (PBPK) model of sorafenib for investigating the effect of sorafenib parameters in hepatorenal impairment
Internship Report Frances Okibedi (supervisor: Matthias König)
Internship report, July 2024
2023 Eleven Strategies for Making Reproducible Research and Open Science Training the Norm at Research Institutions
Friederike E Kohrs, Susann Auer, Alexandra Bannach-Brown, Susann Fiedler, Tamarinde Laura Haven, Verena Heise, Constance Holman, Flavio Azevedo, René Bernard, Armin Bleier, Nicole Bössel, Brian Patrick Cahill, Leyla Jael Castro, Adrian Ehrenhofer, Kristina Eichel, Maximillian Frank, Claudia Frick, Malte Friese, Anne Gärtner, Kerstin Gierend, David Joachim Grüning, Lena Hahn, Maren Hülsemann, Malika Ihle, Sabrina Illius, Laura König, Matthias König, Louisa Kulke, Anton Kutlin, Fritjof Lammers, David MA Mehler, Christoph Miehl, Anett Müller-Alcazar, Claudia Neuendorf, Helen Niemeyer, Florian Pargent, Aaron Peikert, Christina U Pfeuffer, Robert Reinecke, Jan Philipp Röer, Jessica L Rohmann, Alfredo Sánchez-Tójar, Stefan Scherbaum, Elena Sixtus, Lisa Spitzer, Vera Maren Straßburger, Marcel Weber, Clarissa J Whitmire, Josephine Zerna, Dilara Zorbek, Philipp Zumstein, Tracey L Weissgerber
eLife (2023) 12:e89736.. doi:10.7554/eLife.89736
2023 Insights into Intestinal P-glycoprotein Function using Talinolol: A PBPK Modeling Approach
Beatrice Stemmer Mallol, Jan Grzegorzewski, Matthias König
bioRxiv 2023.11.21.568168 (preprint). doi:10.1101/2023.11.21.568168
2023 A pathway model of glucose-stimulated insulin secretion in the pancreatic β-cell
Maheshvare MD., Raha S., König M.*, and Pal D.* (* equal contribution)
Front. Endocrinol. 14:1185656. doi:10.3389/fendo.2023.1185656
2023 A physiologically based pharmacokinetic (PBPK) model of the probe drug talinolol for the characterization of intestinal P-glycoprotein
Bachelor Thesis Beatrice Stemmer Mallol (supervisor: Matthias König)
Bachelor Thesis, July 2023
2023 A physiologically based pharmacokinetic model for CYP2E1 phenotyping via chlorzoxazone
J. Küttner, J. Grzegorzewski, HM. Tautenhahn, M. König
bioRxiv 2023.04.12.536571 (preprint). doi:10.1101/2023.04.12.536571
2023 Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2022 and the COMBINE meeting 2022
M. König, P. Gleeson, M. Golebiewski, T. Gorochowski, M. Hucka, S. Keating, C. Myers, D. Nickerson, F. Schreiber
J Integr Bioinform. 2023 Mar 29;20(1).. doi:10.1515/jib-2023-0004. pmid:36989443
2023 standard-GEM: standardization of open-source genome-scale metabolic models
Mihail Anton, Eivind Almaas, Rui Benfeitas, Sara Benito-Vaquerizo, Lars M. Blank, Andreas Dräger, John M. Hancock, Cheewin Kittikunapong, Matthias König, Feiran Li, Ulf W. Liebal, Hongzhong Lu, Hongwu Ma, Radhakrishnan Mahadevan, Adil Mardinoglu, Jens Nielsen, Juan Nogales, Marco Pagni, Jason A. Papin, Kiran Raosaheb Patil, Nathan D. Price, Jonathan L. Robinson, Benjamín J. Sánchez, Maria Suarez-Diez, Snorre Sulheim, L. Thomas Svensson, Bas Teusink, Wanwipa Vongsangnak, Hao Wang, Ahmad A. Zeidan, Eduard J. Kerkhoven
bioRxiv 2023.03.21.512712 (preprint). doi:10.1101/2023.03.21.512712
2023 Simvastatin therapy in different subtypes of hypercholesterolemia - a physiologically based modelling approach
F. Bartsch, J. Grzegorzewski, H. Pujol, HM. Tautenhahn, M. König
medRxiv 2023.02.01.23285358 (preprint). doi:10.1101/2023.02.01.23285358
2023 Physiologically based pharmacokinetic (PBPK) modeling for dynamical liver function tests and CYP phenotyping
Jan Grzegorzewski (supervisor: Matthias König)
PhD Thesis, Jan 2023 (submitted)
2023 libRoadRunner 2.0: A High-Performance SBML Simulation and Analysis Library
Ciaran Welsh, Jin Xu, Lucian Smith, Matthias König, Kiri Choi, Herbert M. Sauro
Bioinformatics. 2023 Jan 1;39(1):btac770. doi:10.1093/bioinformatics/btac770. pmid:36478036
2022 Cytochrome p450 enzymes in periportal steatosis: Modulation of drug metabolizing activity but not of pericentral expression pattern
M. Albadry, S. Höpfl, N. Ehteshamzad, M. König, M. Böttcher, J. Neumann, A. Lupp, O. Dirsch, N. Radde, B. Christ, M. Christ, L.O. Schwen, H. Laue, R. Klopfleisch and Uta Dahmen
Sci Rep. 2022 Dec 17;12(1):21825. doi:10.1038/s41598-022-26483-6. pmid:36528753
2022 Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan
Grzegorzewski, J., Brandhorst, J., König, M.
Front Pharmacol. 2022 Oct 24;13:1029073. doi:10.3389/fphar.2022.1029073. pmid:36353484
2022 FAIR Sharing of Reproducible Models of Epidemic and Pandemic Forecast
Ramachandran, K.*; König, M.*; Scharm, M.; Nguyen, T.V.N.; Hermjakob, H.; Waltemath, D.; Malik Sheriff, R.S. (* equal contribution)
Preprints 2022, 2022060137 (preprint). doi:10.20944/preprints202206.0137.v1
2022 BioSimulators: a central registry of simulation engines and services for recommending specific tools
Shaikh B, Smith LP, Vasilescu D, Marupilla G, Wilson M, Agmon E, Agnew H, Andrews SS, Anwar A, Beber ME, Bergmann FT, Brooks D, Brusch L, Calzone L, Choi K, Cooper J, Detloff J, Drawert B, Dumontier M, Ermentrout GB, Faeder JR, Freiburger AP, Fröhlich F, Funahashi A, Garny A, Gennari JH, Gleeson P, Goelzer A, Haiman Z, Hasenauer J, Hellerstein JL, Hermjakob H, Hoops S, Ison JC, Jahn D, Jakubowski HV, Jordan R, Kalaš M, König M, Liebermeister W, Sheriff RSM, Mandal S, McDougal R, Medley JK, Mendes P, Müller R, Myers CJ, Naldi A, Nguyen TVN, Nickerson DP, Olivier BG, Patoliya D, Paulevé L, Petzold LR, Priya A, Rampadarath AK, Rohwer JM, Saglam AS, Singh D, Sinha A, Snoep J, Sorby H, Spangler R, Starruß J, Thomas PJ, van Niekerk D, Weindl D, Zhang F, Zhukova A, Goldberg AP, Schaff JC, Blinov ML, Sauro HM, Moraru II, Karr JR.
Nucleic Acids Res. 2022 May 7;50(W1):W108–14. doi:10.1093/nar/gkac331. pmid:35524558
2022 A physiologically based model of pravastatin - The role of genotypes and hepatic or renal impairment on the pharmacokinetics of pravastatin
Helena Leal Pujol (supervisor: Matthias König)
Bachelor Thesis, May 2022
2022 Dynamic Flux Balance Analysis Models in SBML
Matthias König*, Leandro H. Watanabe*, Jan Grzegorzewski, and Chris J. Myers
* equal contribution
bioRxiv 245076 (preprint, submitted). doi:10.1101/245076
2022 Pharmacokinetics of caffeine: A systematic analysis of reported data for application in metabolic phenotyping and liver function testing
Jan Grzegorzewski, Florian Bartsch, Adrian Köller, and Matthias König
Frontiers in Pharmacology 2022, Vol12. doi:10.3389/fphar.2021.752826. pmid:35280254
2021 Prediction of survival after hepatectomy using a physiologically based pharmacokinetic model of indocyanine green liver function tests
Adrian Köller, Jan Grzegorzewski, Michael Tautenhahn, Matthias König
Front. Physiol., 22 November 2021. doi:10.3389/fphys.2021.730418. pmid:34880771
2021 Physiologically based modeling of the effect of physiological and anthropometric variability on indocyanine green based liver function tests
Adrian Köller, Jan Grzegorzewski and Matthias König
Front Physiol. 2021 Nov 22;12:757293. doi:10.3389/fphys.2021.757293. pmid:34880776
2021 Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function
Bruno Christ∗, Maximilian Collatz*, Uta Dahmen*, Karl-Heinz Herrmann*, Sebastian Höpfl*, Matthias König*, Lena Lambers*, Manja Marz*, Daria Meyer*, Nicole Radde*, Jürgen R. Reichenbach*, Tim Ricken*, and Hans-Michael Tautenhahn* (* equal contribution)
Front Physiol. 2021 Nov 18;12:733868. doi:10.3389/fphys.2021.733868. pmid:34867441
2021 Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2021
F. Schreiber, P. Gleeson, M. Golebiewski, T. Gorochowski, M. Hucka, S. Keating, M. König, C. Myers, D. Nickerson, D. Walthemath
J Integr Bioinform. 2021 Oct 22;18(3):20210026. doi:10.1515/jib-2021-0026. pmid:34674411
2021 Computational modelling of omeprazole - pharmacokinetics and pharmacodynamics
Sükrü Balci (supervisor: Matthias König)
Bachelor Thesis, October 2021
2021 SBMLWebApp: Web-based Simulation, Steady-State Analysis, and Parameter Estimation of Systems Biology Models
Takahiro G. Yamada, Kaito Ii, Matthias König, Martina Feierabend, Andreas Dräger, and Akira Funahashi
Processes 9, no. 10: 1830. doi:10.3390/pr9101830
2021 The simulation experiment description markup language (SED-ML): language specification for level 1 version 4
Smith, Lucian P., Bergmann, Frank T., Garny, Alan, Helikar, Tomáš, Karr, Jonathan, Nickerson, David, Sauro, Herbert, Waltemath, Dagmar and König, Matthias.
Journal of Integrative Bioinformatics, vol. 18, no. 3, 2021, pp. 20210021. doi:10.1515/jib-2021-0021. pmid:35330701
2021 The Systems Biology Simulation Core Library
Panchiwala, H.; Shah, S.; Planatscher, H.; Zakharchuk, M.; König, M.; Dräger, A.
Bioinformatics. 2022 Jan 12;38(3):864-865. doi:10.1093/bioinformatics/btab669. pmid:34554191
2021 Ten Simple Rules for FAIR Sharing of Experimental and Clinical Data with the Modeling Community
Matthias König*, Jan Grzegorzewski, Martin Golebiewski, Henning Hermjakob, Mike Hucka, Brett Olivier, Sarah M. Keating, David Nickerson, Falk Schreiber, Rahuman Sheriff, Dagmar Waltemath
Preprints 2021, 2021080303 (in revision). doi:10.20944/preprints202108.0303.v2
2021 OMEX Metadata Specification Version 1.2
John Gennari, Matthias König, Goskel Misirli, Maxwell Neal, David Nickerson, Dagmar Waltemath
J Integr Bioinform. 2021 Oct 20;18(3):20210020. doi:10.1515/jib-2021-0020. pmid:34668356
2021 SED-ML Validator: tool for debugging simulation experiments
Bilal Shaikh, Andrew Philip Freiburger, Matthias König, Frank T. Bergmann, David P. Nickerson, Herbert M. Sauro, Michael L. Blinov, Lucian P. Smith, Ion I. Moraru, Jonathan R. Karr
arXiV, 2021, 2106.00844 (preprint, submitted). doi:10.48550/arXiv.2106.00844
2021 A Physiologically Based Model of Indocyanine Green Liver Function Tests - Effects of Physiological Factors, Hepatic Disease and Hepatic Surgery
Adrian Köller (supervisor: Matthias König)
Bachelor Thesis, March 2021
2020 QuaLiPerF – Multi-X Liver Modelling
Tim Ricken, Lena Lambers, Bruno Christ, Uta Dahmen, Karl-Heinz Herrmann, Matthias König, Manja Marz, Nicole Radde, Jürgen R. Reichenbach, Lars Ole Schwen & Hans-Michael Tautenhahn
GACM - German Association for Computational Mechanics Report, winter 2020: No. 13
2020 Computational Modelling of Simvastatin - Effects on HMG-CoA Reductase Activity and Cholesterol
Florian Bartsch (supervisor: Matthias König)
Bachelor Thesis, November 2020
2020 Computational Modelling of Midazolam Clearance: Effect of Inhibitors and Inducers
Yannick Duport (supervisor: Matthias König)
Bachelor Thesis, August 2020
2020 PK-DB: pharmacokinetics database for individualized and stratified computational modeling
Grzegorzewski J, Brandhorst J, Green K, Eleftheriadou D, Duport Y, Barthorscht F, Köller A, Ke DYJ, De Angelis S, König M.
Nucleic Acids Res. 2021 Jan 8;49(D1):D1358-D1364. doi:10.1093/nar/gkaa990. pmid:33151297
2020 SBML Level 3: an extensible format for the exchange and reuse of biological models
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, and SBML Community members
Mol Syst Biol. 2020;16(8):e9110. doi:10.15252/msb.20199110. pmid:32845085
2020 Open modeling and exchange (OMEX) metadata specification version 1.0
Neal ML, Gennari JH, Waltemath D, Nickerson DP, König M
J Integr Bioinform. 2020 Jun 25;17(2-3):20200020. doi:10.1515/jib-2020-0020. pmid:32589606
2020 Specifications of Standards in Systems and Synthetic Biology:Status and Developments in 2020
F. Schreiber, B. Sommer, G. Bader, P. Gleeson, M. Golebiewski, T. Gorochowski, M. Hucka, S. Keating, M. König, C. Myers, D. Nickerson, D. Walthemath
J Integr Bioinform. 2020 Jun 29;17(2-3):20200022. doi:10.1515/jib-2020-0022
2020 The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE)
D Waltemath, M Golebiewski, M Blinov, P Gleeson, H Hermjakob, E Inau, S Keating, M König, O Krebs, R Malik-Sheriff, D Nickerson, E Oberortner, H Sauro, F Schreiber, L Smith, M Stefan, U Wittig, C Myers
J Integr Bioinform. 2020 Jun 29;17(2-3):20200005. doi:10.1515/jib-2020-0005
2020 The Distributions Package for SBML Level 3
L Smith, S Moodie, F Bergmann, C Gillespie, S Keating, M. König, C Myers, M Swat, D Wilkinson, M Hucka
J Integr Bioinform. 2020 Jul 20;17(2-3):20200018. doi:10.1515/jib-2020-0018. pmid:32750035
2020 MEMOTE for standardized genome-scale metabolic model testing
Christian Lieven, Moritz Emanuel Beber, Brett G. Olivier, Frank T. Bergmann, Meric Ataman, Parizad Babaei, Jennifer A. Bartell, Lars M. Blank, Siddharth Chauhan, Kevin Correia, Christian Diener, Andreas Dräger, Birgitta Elisabeth Ebert, Janaka N. Edirisinghe, Jose P. Faria, Adam Feist, Georgios Fengos, Ronan M. T. Fleming, Beatriz Garcia-Jimenez, Vassily Hatzimanikatis, Wout van Helvoirt, Christopher Henry, Henning Hermjakob, Markus J. Herrgard, Hyun Uk Kim, Zachary King, Jasper Jan Koehorst, Matthias König, Steffen Klamt, Edda Klipp, Meiyappan Lakshmanan, Nicolas Le Novere, Dong-Yup Lee, Sang Yup Lee, Sunjae Lee, Nathan E. Lewis, Hongwu Ma, Daniel Machado, Radhakrishnan Mahadevan, Paulo Maia, Adil Mardinoglu, Greg L. Medlock, Jonathan Monk, Jens Nielsen, Lars K. Nielsen, Juan Nogales, Intawat Nookaew, Osbaldo Resendis, Bernhard Palsson, Jason A. Papin, Kiran Raosaheb Patil, Mark Poolman, Nathan D. Price, Anne Richelle, Isabel Rocha, Benjamin Sanchez, Peter Schaap, Rahuman S. Malik Sheriff, Saeed Shoaie, Nikolaus Sonnenschein, Bas Teusink, Paulo Vilaca, Jon Olav Vik, Judith A. Wodke, Joana C. Xavier, Qianqian Yuan, Maksim Zakhartsev, Cheng Zhang
Nat Biotechnol. 2020;38(3):272-276. doi:10.1038/s41587-020-0446-y. pmid:32123384
2020 Executable Simulation Model of the Liver
Matthias König
bioRxiv 2020.01.04.894873 (preprint). doi:10.1101/2020.01.04.894873v1
2019 Model Order Reduction (MOR) of Function-Perfusion-Growth Simulation in the Human Fatty Liver via Artificial Neural Network (ANN)
Lambers L., Ricken T., and König M.
Proceedings in Applied Mathematics & Mechanics, PAMM, 2019. doi:10.1002/pamm.201900429
2019 Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2019
F Schreiber, G Bader, P Gleeson, M Golebiewski, M Hucka, SM Keating, M König, C Myers, D Nickerson, B Sommer, D Waltemath
J Integr Bioinform. 2019 Jul 13;16(2). doi:10.1515/jib-2019-0035. pmid:31301675
2019 The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core
M. Hucka, F. Bergmann, C. Chaouiya, A. Dräger, S. Hoops, S. Keating, M. König, N Le Novere, C. Myers, B. Olivier, S. Sahle, J. Schaff, R. Sheriff, L. Smith, D. Waltemath, D. Wilkinson, F. Zhang
J Integr Bioinform. 2019 Jun 20;16(2);. doi:10.1515/jib-2019-0021. pmid:31219795
2018 Tellurium: An Extensible Python-based Modeling Environment for Systems and Synthetic Biology
Choi K., Medley K., König M., Stocking K., Smith L., Gu S., and Sauro HM.
Biosystems. 2018 Jul 24. pii: S0303-2647(18)30125-4. doi:10.1016/j.biosystems.2018.07.006. pmid:30053414
2018 HEPATOKIN1: A Biochemistry-Based Model of Liver Metabolism Suited for Applications in Medicine and Pharmacology
Berndt N., Bulik S., Wallach I., Wünsch T., König M., Stockmann M., Meierhofer M., Holzhütter HG.
Nat Commun. 2018 Jun 19;9(1):2386.. doi:10.1038/s41467-018-04720-9. pmid:29921957
2018 Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 3 (L1V3)
Bergmann, FT., Cooper, J., König, M.*, Moraru, I., Nickerson, D., Le Novère N., Olivier, BG., Sahle, S., Smith, L., Waltemath, D.
* corresponding author
J Integr Bioinform. 2018 Mar 19;15(1). doi:10.1515/jib-2017-0086. pmid:29550789
2018 Harmonizing semantic annotations for computational models in biology
Neal, M.; König, M.; Nickerson, D.; Misirli, G.; Kalbasi, R.; Dräger, A.; Atalag, K.; Chelliah, V.; Cooling, M.; Cook, D.; Crook, S.; de Alba, M.; Friedman, S.; Garny, A.; Gennari, J.; Gleeson, P.; Golebiewski, M.; Hucka, M.; Juty, N.; Novère, N. L.; Myers, C.; Olivier, B.; Sauro, H.; Scharm, M.; Snoep, J.; Touré, V.; Wipat, A.; Wolkenhauer, O. & Waltemath, D.
Brief Bioinform. 2019 Mar 22;20(2):540-550. doi:10.1093/bib/bby087. pmid:30462164
2018 Tellurium Notebooks — An Environment for Reproducible Dynamical Modeling in Systems Biology.
Medley K., Choi K., König M., Smith L., Gu S., Hellerstein J., Sealfon S., and Sauro HM.
PLoS Comput Biol. 2018 Jun 15;14(6):e1006220. doi:10.1371/journal.pcbi.1006220. pmid:29906293
2017 Computational Modeling in Liver Surgery
Christ, B.*, Dahmen, U.*, Herrmann, K.H.*, König, M.*, Reichenbach, J.R*., Ricken, T.*, Schleicher, J.*, Ole Schwen, L.*, Vlaic, S.* and Waschinsky, N.*
* equal contribution
Front Physiol. 2017 Nov 14;8:906. doi:10.3389/fphys.2017.00906. pmid:29249974
2016 Challenges and opportunities for system biology standards and tools in medical research
König M.*, Oellrich A.*, Waltemath D.*, Dobson R., Hubbard T., and Wolkenhauer O.
* equal contribution
ODLS, p1-6, 2016; article
2016 cy3sabiork: A Cytoscape app for visualizing kinetic data from SABIO-RK
König M.
[version 1; referees: awaiting peer review]. F1000Research 2016, 5:1736. doi:10.12688/f1000research.9211.1
2016 Toward community standards and software for whole-cell modeling
Wholecell Consortium (König M.)
IEEE Trans Biomed Eng. 2016 Jun 10.. doi:10.1109/TBME.2016.2560762. pmid:27305665
2015 Pathobiochemical signatures of cholestatic liver disease in bile duct ligated mice
Kerstin A.*, König M.*, Hoppe A., Thomas M., Müller I., Ebert M., Weng H., Holzhütter HG., Zanger UM., Bode J., Vollmar B. and Dooley S.
* equal contribution
BMC Syst Biol. 2015 Nov 20;9(1):83.. doi:10.1186/s12918-015-0229-0. pmid:26589287
2015 On the Influence of Growth in Perfusion Dependent Biological Systems - at the Example of the Human Liver.
Werner D., Ricken T., Dahmen U., Dirsch O., Holzhütter HG., König M.
PAMM 15 (1), 119-120, 2015. doi:10.1002/pamm.201510050
2015 LibRoadRunner: a high performance SBML simulation and analysis library.
Somogyi ET., Bouteiller JM., Glazier JA., König M., Medley JK., Swat MH and Sauro HM.
Bioinformatics. 2015 Oct 15;31(20):3315-21. doi:10.1093/bioinformatics/btv363. pmid:26085503
2014 Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach.
Ricken T., Werner D., Holzhütter HG., König M., Dahmen U., Dirsch O.
Biomech Model Mechanobiol. 2015 Jun;14(3):515-36. doi:10.1007/s10237-014-0619-z. pmid:25236798
2014 Homeostasis of blood glucose - Computer simulations of central liver functions.
König M. and Holzhütter HG.
systembiologie.de 2014; 8:p.53-57 [PDF (de), PDF (en)]
2013 Metabolic Gradients as Key Regulators in Zonation of Tumor Energy Metabolism: A Tissue-scale Model Based Study.
König M., Holzhütter HG., Berndt N.
Biotechnol J. 2013 Sep;8(9):1058-69.. doi:10.1002/biot.201200393. pmid:23589477
2012 Kinetic Modeling of Human Hepatic Glucose Metabolism in T2DM Predicts Higher Risk of Hypoglycemic Events in Rigorous Insulin Therapy
König M. and Holzhütter HG.
J Biol Chem. 2012 Oct 26;287(44):36978-89. doi:10.1074/jbc.M112.382069. pmid:22977253
2012 CySBML: a Cytoscape plugin for SBML
König M., Dräger A. and Holzhütter HG.
Bioinformatics. 2012 Sep 15;28(18):2402-3. doi:10.1093/bioinformatics/bts432. pmid:22772946
2012 Quantifying the Contribution of the Liver to the Homeostasis of Plasma Glucose: A Detailed Kinetic Model of Hepatic Glucose Metabolism Integrated with the Hormonal Control by Insulin, Glucagon and Epinephrine
König M., Bulik S. and Holzhütter HG.
PLoS Comput Biol. 2012 Jun;8(6):e1002577. Epub 2012 Jun 21.. doi:10.1371/journal.pcbi.1002577. pmid:22761565
2011 Enzymatic Features of the Glucose Metabolism in Tumor Cells.
Herling A, König M, Bulik S, Holzhütter HG.
FEBS J. 2011 Jul;278(14):2436-59. doi:10.1111/j.1742-4658.2011.08174.x. pmid:21564549
2011 FluxViz - Cytoscape Plug-in for Vizualisation of Flux Distributions in Networks
König M. and Holzhütter HG.
Genome Informatics 2010, Vol.24, p.96-103. pmid:22081592
2010 HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology.
Gille C, Bölling C, Hoppe A, Bulik S, Hoffmann S, Hübner K, Karlstädt A, Ganeshan R, König M, Rother K, Weidlich M, Behre J, Holzhütter HG.
Mol Syst Biol. 2010 Sep 7;6:411. doi:10.1038/msb.2010.62. pmid:20823849

News

For details see news.

2024-06-09 Bachelor Thesis Afruja Hossain

Afruja Hossain finished her Bachelor thesis developing a database of CYP and UGT enzymes

2024-06-07 Successful Completion of One-Week Pharmacokinetic Modelling Course

We are excited to announce the successful completion of our one-week intensive course on Pharmacokinetic Modelling, where students delved into principles, drug distribution, clearance, elimination, and various modelling techniques to enhance drug therapy and development.

2024-05-23 New Project Launch via Humboldt Internship Program (HIP): PK-LLM by Prerna Parakkat

We are excited to announce the start of a new project under the Humboldt Internship Program (HIP) by Prerna Parakkat. Prerna will be working on PK-LLM: Implementing a Large Language Model (LLM) as an Expert System for Pharmacokinetic (PK) Data Curation from Scientific Publications.

2024-05-16 Preprint: Cross-Species Variability in Lobular Geometry and Cytochrome P450 Hepatic Zonation: Insights into CYP1A2, CYP2E1, CYP2D6 and CYP3A4

Our latest publication on 'Cross-Species Variability in Lobular Geometry & Cytochrome P450 Hepatic Zonation' reveals insights into liver function across species using WSI technology.

2024-04-15 New projects: Nike Nemitz and Yusuf Ali Kulanoglu start PBPK Modeling Projects

Nike Nemitz and Yusuf Ali Kulanoglu will develop PBPK models for dapagliflozin and aliskiren, respectively, aiming to enhance understanding of pharmacokinetics and pharmacodynamics in diabetes and cardiovascular treatments.

2024-04-15 Publication: The Simulation Experiment Description Markup Language (SED-ML): Language Specification for Level 1 Version 5

Level 1 Version 5 of SED-ML enhances the ability to annotate, archive, share, and reproduce computational simulation experiments by allowing modelers to define tasks, model changes, ranges, and outputs using the Kinetic Simulation Algorithm Ontology (KiSAO).

2024-05-05 Master Thesis Shubhankar Palwankar

Shubhankar Palwankar defended his Master Thesis developing a PBPK model of enalapril

2024-03-29 New multiscale liver model unveils zonation-function dynamics in Drug-Induced Liver Injury (DILI).

We're excited to announce the preprint of our latest research, 'Simulation of zonation-function relationships in the liver using coupled multiscale models: Application to drug-induced liver injury.' This study introduces a multiscale digital twin of the liver, integrating models from cellular to lobular scales, and sheds light on how liver zonation patterns influence drug-induced liver injury.

2024-03-01 PBPK Model of Morphine Project

New Internship Project Launch: Development of a Physiologically Based Pharmacokinetics Model of Morphine. Deepa supported by Rohini and Rohit will develop a PBPK model of morphine.

2024-02-01 Mariia Myshkina has started her PhD in the ATLAS project.

We welcome Mariia to our team who will be working on computational modeling of the liver within ATLAS.

2024-01-18 Participation in the First EDITH-CSA Ecosystem Meeting - Advancing the Virtual Human Twin

We participated in the first EDITH-CSA 'Ecosystem meeting on building the Virtual Human Twin was held at the École Polytechnique de Paris on January 18 and 19, 2024.

2023-11-03 Eleven Strategies for Making Reproducible Research and Open Science Training the Norm at Research Institutions

We are pleased to announce our latest paper in eLife that provides a roadmap for integrating reproducible research and open science practices into academic work.

2023-11-03 Your Dietary Digitial Twin (DDtwin)

Advancing Precision Nutrition: Workshop Success on Dietary Digital Twin, a workshop in Leiden from 30 October - 3 November 2023.

2023-10-31 Humboldt Internship Program 2024 - Computational Modeling of Drug Detoxification - A Systems Medicine Approach

We offer Internships in 2024, academic three-month research stays at Humboldt-Universität zu Berlin. The application for the Summer Term Internships 2024 is open from 03 November to 10 December 2023.

2023-10-10 e:Med Meeting 2023 on Systems Medicine: Quantifying Fat Zonation in Liver Lobules: An Integrated Multiscale In-silico Model

We successfully presented our research on reproducible digital twins for personalized liver function assessment at the e:Med Meeting 2023 on Systems Medicine.

2023-09-18 Preprint: Quantifying Fat Zonation in Liver Lobules: An Integrated Multiscale In-silico Model

Our latest preprint is now out: An integrated multiscale model for quantifying fat zonation in liver lobules.

2023-08-28 Hannah Menghis from Brown University starts her internship

We welcome Hannah Menghis who will establish a PBPK model of semaglutide.

2023-08-02 A pathway model of glucose-stimulated insulin secretion in the pancreatic β-cell

Our latest publication is now on Frontiers of Endocrinology: A pathway model of glucose-stimulated insulin secretion in the pancreatic β-cell

2023-07-17 Bachelor Thesis Beatrice Stemmer Mallol

Beatrice Stemmer Mallol submitted her Bachelor thesis developing a PBPK model of talinolol

2023-07-07 PhD Defense of Jan Grzegorzewski

Jan Grzegorzewski defended his PhD thesis on physiologically based pharmacokinetic modeling (PBPK) for dynamical liver function tests and Cytochrome P450 (CYP) phenotyping.

2023-07-01 Xenia Petukhova and Zahra Bahri start Humboldt Internship Program

Humboldt Internship Program 2023 - Computational Modeling of Drug Detoxification - A Systems Medicine Approach

2023-06-16 Keynote: Advancing Liver Function Assessment: Personalized and Stratified Approaches with Standardized Computational Models and Data

Keynote talk at the Workshop on Computational Models in Biology and Medicine 2023 organized by Nicole Radde and Sebastian Höpfl.

2023-05-28 Preprint: Eleven Strategies for Making Reproducible Research and Open Science Training the Norm at Research Institutions

We present 11 strategies for making #OpenScience & #ReproducibleResearch the norm at research institutions, with tips for implementation & resources. Let's join hands to make these practices standard in the scientific community!

2023-04-16 Preprint: A physiologically based pharmacokinetic model for CYP2E1 phenotyping via chlorzoxazone

Our latest preprint is now on bioRxiv: A physiologically based pharmacokinetic model for CYP2E1 phenotyping via chlorzoxazone

2023-04-03 Michael Stifel Price to promote interdisciplinary, data-driven research

M. Albadry, S. Höpfl, and M. König won the QuaLiPerF Michael Stifel Price for interdisciplinary, data-driven research.

2023-03-29 Publication: Specifications of standards in systems and synthetic biology: status and developments in 2022 and the COMBINE meeting 2022

Our overview of specifications in systems and synthetic biology with a brief overview of the COMBINE 2022 is available.

2023-02-12 PBPK modelling of sorafenib and Gd-EOB-DTPA

Frances Okibedi and Narudeem Sojimade will develop models of the anticancer drug sorafenib in HCC and the liver contrast agent Gd-EOB-DTPA.

2023-02-12 X-Research Group - Digital twins for the treatment of hypertension

M. König receives funding of the Berlin University Alliance and the DFG for the X-Student Research Group: Digital twins for the treatment of hypertension

2023-02-07 M. König has been elected as PEtab editor (2023-2026)

Proud to be elected editor for PEtab, a data format for specifying parameter estimation problems in systems biology.

2023-02-03 Preprint: Simvastatin therapy in different subtypes of hypercholesterolemia

Our latest preprint is now on medRxiv: Simvastatin therapy in different subtypes of hypercholesterolemia - a physiologically based modelling approach.

2023-02-01 ATLAS - AI and Simulation for Tumor Liver ASsessment

The BMBF is funding our joint project ATLAS in the "Computational Life Sciences - AI Methods for Systems Medicine".

2022-11-17 New Bachelor Student - Afruja Hossain

Afruja Hossain started working in our lab on a systematic overview of the protein variability of cytochrome P450 (CYP450) isoforms in the human liver.

2022-11-15 Visiting EU parliament and attending STOA AI session

We were selected to participate in an European policy journey on the topic EU research funding and science communication by the Berlin University Alliance (BUA).