Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function

Daehee Hwang, George Stephanopoulos, Christina Chan

Research output: Contribution to journalArticle

  • 17 Citations

Abstract

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.

LanguageEnglish (US)
Pages487-499
Number of pages13
JournalBioinformatics
Volume20
Issue number4
DOIs
StatePublished - Mar 1 2004

Profile

Inverse Modeling
Multiblock
Environmental Factors
Least-Squares Analysis
Partial Least Squares
Metabolic Flux Analysis
Artificial Liver
Tissue
Fluxes
Equipment and Supplies
Metabolome
Bioelectric potentials
Tissue Engineering
Metabolic Networks and Pathways
Cell
Tissue engineering
Urea
Liver
Lipids
Hepatocytes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Computer Science Applications
  • Computational Theory and Mathematics

Cite this

Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function. / Hwang, Daehee; Stephanopoulos, George; Chan, Christina.

In: Bioinformatics, Vol. 20, No. 4, 01.03.2004, p. 487-499.

Research output: Contribution to journalArticle

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