The virtual liver: a multidisciplinary, multilevel challenge for systems biology

Abstract

The liver is the central metabolic organ in human physiology, with functions that are fundamentally important to the detoxification of xenobiotics (drugs), the maintenance of homeostasis of numerous blood metabolites, and the production of mediators of the acute phase response. Liver toxicity, whether actual or implied is the reason for the failure of a significant proportion of many promising novel medicines that consequently never reach the market, and diseases such as atherosclerosis, diabetes, and fatty liver diseases, that are a major burden on current health resources, are directly linked to functional and structural disorders of the liver. This article presents the concepts and approaches underpinning one of the most exciting and ambitious modeling projects in the field of systems biology and systems medicine. This major multidisciplinary research program is aimed at developing a whole-organ model of the human liver, representing its central physiological functions under normal and pathological conditions The model will be composed of a larger battery of interconnected submodels representing liver anatomy and physiology, integrating processes across hierarchical levels in space, time, and structural organization. In this article, we outline the general architecture of the liver model and present first step taken to reach this ambitious goal.

Future of Medicine: Models in Predictive Diagnostics and Personalized Medicine

“…The Virtual Liver Network (www. virtual-liver.de) followed this approach as a multidisciplinary research programme aiming at the development of a whole-organ model of the human liver and describing the physiological functions under normal and pathological conditions [49,50]. The Virtual Physiological Human is a European scale initiative developing patient-specific computer models for personalized and predictive health care.…”

“…Physiological models are based on metabolic information and integrate population data that have clinical relevance [49]. Physiological models study the dynamic processes and the functional behavior of the physiological state of a tissue, an organ, or even an organism.…”

A physiome interoperability roadmap for personalized drug development

“…virtual-liver.de) (VLN) to more detailed vascular models of the hepatic sinusoids [46,47] and to multiscale and biophysically based models of physiological liver function [48,49]. Similar work is being done for the heart [40].…”

Model Prediction and Validation of an Order Mechanism Controlling the Spatiotemporal Phenotype of Early Hepatocellular Carcinoma

“…To ensure that the emerging model is able to simulate both liver regeneration after drug-induced central liver lobule damage and early states of hepatocellular carcinoma, we maintained all mechanisms of the liver regeneration model and integrated mechanisms specific to cancer initiation. Prospectively, this shall permit us to construct a virtual liver model that can be used as a tool to perform virtual experiments and explore the consequence of various perturbations and malfunctions in liver (Holzhuetter et al 2012;D'Alessandro et al 2015).…”