Bioinformatics Advance Access originally published online on January 22, 2004
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Bioinformatics 20(4) © Oxford University Press 2004; all rights reserved.
Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function
1 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA and 2 Department of Chemical Engineering and Material Science, Michigan State University, 1257 EB East Lansing, MI 48824, USA
Received on April 21, 2003
; revised on July 29, 2003
; accepted on August 6, 2003
Advance Access Publication January 22, 2004
Motivations: Tissue engineering constitutes an important field with its potential of addressing the current shortage in organ availability. To successfully develop tissue-engineered organs, it is crucial to understand how to maintain the cells under conditions that maximize their ability to perform their physiological roles, regardless of the environment, whether the cells are part of an extracorporeal system, such as the bioartificial liver assist device, or an implantable tissue-engineered device. Our goals are to (1) provide insight into how cells will behave when confronted with changes in its environment and (2) determine the optimal environmental factors to achieve a desired level of cellular function.
Results: Diverse sets of environmental factors were used to systematically perturb the metabolic behavior associated with pre-conditioning and plasma supplementation. To probe metabolic state of hepatocytes, metabolic flux analysis was used to obtain the metabolic profile. We applied a multi-block partial least square (MPLS) model to relate environmental factors and fluxes to levels of intracellular lipids and urea synthesis. The MPLS model identified: (1) the most influential environmental factors and (2) how the metabolic pathways are altered by these factors. Finally, we inverted the MPLS model to determine the concentrations and types of environmental factors required to obtain the most economical solution for achieving optimal levels of cellular function for practical situations.
Supplementary information: Appendices can be accessed at http://www.chems.msu.edu/fac.pub/chan/MPLS_App.pdf
Contact: krischan{at}egr.msu.edu
* To whom correspondence should be addressed.
Current address: Room 232, Institute for Systems Biology, 1441 N 34th St., Seattle, WA 98103, USA
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