Integration from proteins to organs: the IUPS Physiome Project

The IUPS Physiome Project is an internationally collaborative open source project intended to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales and across all organ systems. Here, we illustrate the application of this multi-scale modeling approach to three organ systems: the heart, the lungs and the musculo-skeletal system, and in each case we show how the organ level models incorporate tissue and cell-level physiology. Although the computational physiology framework presented here does not yet incorporate models of ageing processes, the model-based approach is certainly capable of describing ageing and disease-related processes both via parameter changes within the models of normal physiological processes and via models of additional processes added to the framework.     

The Microcirculation Physiome Project

Presented is a discussion of steps towards the creation of a database of the microcirculation encompassing anatomical and functional experimental data, and conceptual and computational models. The discussion includes issues of database utility, organization, data deposition, and linkage to other databases. The database will span levels from gene to tissue and will serve both research and educational purposes. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 0130Cc     

Systems approaches to the networks of aging

The aging of an organism is the result of complex changes in structure and function of molecules, cells, tissues, and whole body systems. To increase our understanding of how aging works, we have to analyze and integrate quantitative evidence from multiple levels of biological organization. Here, we define a broader conceptual framework for a quantitative, computational systems biology approach to aging. Initially, we consider fractal supply networks that give rise to scaling laws relating body mass, metabolism and lifespan. This approach provides a top-down view of constrained cellular processes. Concomitantly, multi-omics data generation build such a framework from the bottom-up, using modeling strategies to identify key pathways and their physiological capacity. Multiscale spatio-temporal representations finally connect molecular processes with structural organization. As aging manifests on a systems level, it emerges as a highly networked process regulated through feedback loops between levels of biological organization.     

Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity

One of the major aims of the Tnternational Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health.We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically,we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach.     

欧洲虚拟生理人

虚拟生理人(VPH)项目由欧盟强力支持，致力于人体生理在各层面的全身完整模型的建立，从器官、组织、细胞和分子水平到基因水平。该项目从STEP项目率先实施，由欧盟资助下的协调行动从2006年初正式启动。作者介绍了VPH项目及其最近通过physiome平台在世界范围的快速发展。最后，着重介绍了VPH项目在骨肌系统的一个子项目－Living Human项目和其在世界各地的类似的研究探索。     

Transport and Reaction at Endothelial Plasmalemma: Distinguishing Intra- From Extracellular Events

The pulmonary endothelium is a chemical reactor that modifies blood composition in several ways, including reduction of the oxidized forms of certain redox active substances in the blood. The physiological functions of the transplasma membrane electron transport systems involved in the latter are not fully understood, but an argument is made that they are involved in antioxidant defense. In addition, the experimental approaches used to characterize the process, including studies at whole organ, cell culture, and subcellular levels, along with the use of mathematical modeling, may be representative of the physiome concept wherein a goal is the integration of information obtained at all levels of biological organization. In this article, separation of intra- and extracellular events involved in the disposition of redox active probes within the lungs is the particular example. © 2000 Biomedical Engineering Society. PAC00: 8716Uv, 8716Dg, 8715Rn, 8719Uv     

A “Geographic Information Systems” Based Technique for the Study of Microvascular Networks

An automated system (ANET) has been developed to construct interactive maps of microvascular networks, calculate blood flow parameters, and simulate microvascular network blood flow using the geographic information systems (GIS) technology. ANET enables us to automatically collect and display topological, structural, and functional parameters and simulate blood flow in microvascular networks. The user-definable programming interface was used for the manipulation of drawings and data. Visual enhancement techniques such as color can be used to display useful information within a network. In ANET the network map becomes a graphical interface through which network information is stored and retrieved and simulations of microvascular network blood flow are carried out. We have used ANET to study the effects of ionizing radiation on normal tissue microvascular networks. Our results indicate that while vessel diameters significantly increased with age in control animals they decreased in irradiated animals. The tortuosity of irradiated vessels (16.3 ± 1.1 mean±standard error of the mean) was significantly different from control vessels (10.0 ± 1.3) only at 7 days postirradiation. Average red blood cell transit time was significantly different between control (1.6 ± 0.6 s) and irradiated (10.7 ± 5.7 s) microvascular networks at 30 days postirradiation. ANET provides an effective tool for handling the large volume of complex data that is usually obtained in microvascular network studies and for simulating blood flow in microvascular networks. © 1999 Biomedical Engineering Society. PAC99: 8764-t, 8719Tt, 0705Pj, 8750Gi     

Systems biology,the Physiome Project and oriental medicine

Systems biology, particularly at the higher levels that are the domain of the Physiome Project, offers a more promising basis for constructive dialogue with traditional oriental medicine than does reductive molecular biology alone. However, there are major problems to be overcome before this can be achieved. First, systems biology is at an early stage of development as a fully quantitative and computational discipline. We still do not know what the higher level concepts should be that might map well to traditional oriental medical concepts. Second, there are major problems of translation and interpretation to be tackled. Exploring the full semantic frame of the oriental concepts will be necessary before mapping to concepts in western medicine can be useful.     

The Coronary Vasculature and its Reconstruction

Recently, we have developed several new innovations in the morphometry of vascular trees. These innovations have been used to study the anatomy of the coronary circulation in the pig and have yielded a complete set of morphometric data on the entire coronary vasculature. Since, the innovations are applicable to any organ that has a tree-like vasculature, their utility in describing the quantitative anatomy of intraorgan vasculature is evident. These advancements in morphometry along with the automation of vascular tree reconstruction, data analysis, and hemodynamic applications should make the data base on intraorgan vasculature more abundant and more useful. The morphometric data will contribute to the Circulatory Network Physiome that will serve as an anatomical basis for the Physiome Project. This article covers several topics: (1) intraorgan vascular trees in terms of their anatomy, mechanical properties, physiological behavior, and adaptation, (2) reconstruction of the coronary vasculature, and (3) some of the shortcomings of the present morphometric data base and some proposed remedies. Finally, a discussion of the constitution of the circulatory network physiome in terms of the available morphometric data on intraorgan vasculature will be presented. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8719Rr