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Multi-level modeling

Since the inception of ISB group (in 2009), we have developed all of our organ models with the long-term goal that they should become a part of our multi-level whole-body models. Our modular approach to connecting organ models with each other was first presented in (Nyman, 2011). The basic idea is to define the input-output profile for each organ, and then have different versions of each organ model, which all fulfill these input-output profiles. In practice, the best way to characterize these input-output profiles is to measure them directly. This can be done using so-called arteriovenous difference data (AV-data). Such AV-data measures both the arterious blood going into an organ and the venous blood leaving the organ. In other words, using such AV-data, we have experimental time-curves describing what each organ is experiencing as input (the arterial blood), and what each organ is doing with the blood (the difference between the arterial and venous blood). We can then construct a simple top-level model, where we have minimal organ models for each organ, that still agree with these AV-data, and which can communicate with each other, based on these input-output profiles. After this, each new organ model can either be included in the big multi-level model, by including it as a sub-model to an existing organ model, or by updating the entire organ-model.

Key references

Tilda Herrgårdh, Hao Li, Elin Nyman, Gunnar Cedersund, (2021). "An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow". Front Physiol. 12:619254. (Take me to the article)

Elin Nyman, Cecilia Brännmark, Robert Palmér, Jan Brugård, Fredrik H Nyström, Peter Strålfors, Gunnar Cedersund (2011). "A hierarchical whole-body modeling approach elucidates the link between in Vitro insulin signaling and in Vivo glucose homeostasis". J Biol Chem. 286(29):26028-41. (Take me to the article)

Tilda Herrgårdh, Christian Simonsson, Mattias Ekstedt, Peter Lundberg, Karin G Stenkula, Elin Nyman, Peter Gennemark, Gunnar Cedersund (2023). "A multi-scale digital twin for adiposity-driven insulin resistance in humans: diet and drug effects". Diabetol Metab Syndr. 15(1):250. (Take me to the article)

Oscar Silfvergren, Christian Simonsson, Mattias Ekstedt, Peter Lundberg, Peter Gennemark, Gunnar Cedersund (2022). "Digital twin predicting diet response before and after long-term fasting". PLoS Comput Biol. 18(9):e1010469. (Take me to the article)

Key personnel

Gunnar Cedersund
Elin Nyman
Oscar Silfvergren
Christian Simonsson
William Lövfors
Tilda Herrgårdh
Henrik Podéus
Kajsa Tunedal