This software development project combines the perspectives and software from three experienced groups to create and maintain what will be the most advanced and complete software package available for systems biology and the analysis of physiological data for research and clinical practice. The project brings together: (1) The JSim system for model based analysis using single or multi-scale models using ordinary and 1- dimensional partial differential equations for transport and metabolism (Butterworth and Bassingthwaighte, University of Washington), (2) the System Biology Workbench and related software coding packages invented by Herbert Sauro (Unversity of Washington), and (3) thermodynamically constrained and detailed equations for biochemical reactions created automatically from databases on reactions equilibria and kinetics (Daniel Beard, Medical College Wisconsin). The coalescence of these three powerful techniques, all of which utilize archival database markup languages like SBML and CellML, will foster model construction using JSim's inbuilt error identification and correction mechanisms. The toolkits and models will be disseminated worldwide in easily understood code, and will provide exactly and directly reproducible solutions on a wide range of computational platforms including Windows, Macintosh, and Linux. The models will be designed for experiment design and analysis, and the open source code for models and the analysis packages will be freely available to investigators everywhere. This powerful combination is relevant to the betterment of health as it provides investigators in genomics, molecular biology, physiology, and pharmacology with practical mechanisms for predicting and understanding integrated cellular organ and body function. Many of the current generation of biologists are not deeply trained in quantitative analysis of complex systems, so the availability of these tools will greatly facilitate their understanding of the biology and their ability to design more precisely targeted experimentation, more efficient data analysis, and improved therapies.

Public Health Relevance

This research will expedite the translation from basic research in genomics, genetic network regulation, biochemical network behavior, and cell function to clinical applications that provide long range public health benefits. It will occur via better directed experimentation through modeling, and through improved prediction of therapy outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB008407-04
Application #
8274847
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Peng, Grace
Project Start
2009-06-01
Project End
2013-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$324,974
Indirect Cost
$110,867
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Smith, Lucian P; Butterworth, Erik; Bassingthwaighte, James B et al. (2014) SBML and CellML translation in antimony and JSim. Bioinformatics 30:903-7
Bassingthwaighte, James B; Chinn, Tamara M (2013) Reexamining Michaelis-Menten enzyme kinetics for xanthine oxidase. Adv Physiol Educ 37:37-48
Jardine, Bartholomew; Bassingthwaighte, James B (2013) Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation. Am J Physiol Lung Cell Mol Physiol 305:L42-55
Alessio, Adam M; Bassingthwaighte, James B; Glenny, Robb et al. (2013) Validation of an axially distributed model for quantification of myocardial blood flow using ýýýýN-ammonia PET. J Nucl Cardiol 20:64-75