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.

    Original languageEnglish (US)
    Pages (from-to)487-499
    Number of pages13
    JournalBioinformatics
    Volume20
    Issue number4
    DOIs
    StatePublished - Mar 1 2004

    Profile

    Environmental factors
    Anthralin
    Least-Squares Analysis
    Multiblock
    Library Catalogs
    Fluxes
    Equipment and Supplies
    Tissue
    Partial least squares
    Cell
    Model
    Myoclonic Cerebellar Dyssynergia
    Callosities
    Bromates
    Apoferritins
    Cerebellar Ataxia
    Metabolic Networks and Pathways
    Fibrin
    Hepatocytes
    Metabolic Flux Analysis

    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

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

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

    Research output: Contribution to journalArticle

    @article{2aebe7e869f545198b2872d73414392d,
    title = "Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function",
    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.",
    author = "Daehee Hwang and George Stephanopoulos and Christina Chan",
    year = "2004",
    month = "3",
    doi = "10.1093/bioinformatics/btg433",
    volume = "20",
    pages = "487--499",
    journal = "Bioinformatics",
    issn = "1367-4803",
    publisher = "Oxford University Press",
    number = "4",

    }

    TY - JOUR

    T1 - Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function

    AU - Hwang,Daehee

    AU - Stephanopoulos,George

    AU - Chan,Christina

    PY - 2004/3/1

    Y1 - 2004/3/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=1542400266&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=1542400266&partnerID=8YFLogxK

    U2 - 10.1093/bioinformatics/btg433

    DO - 10.1093/bioinformatics/btg433

    M3 - Article

    VL - 20

    SP - 487

    EP - 499

    JO - Bioinformatics

    T2 - Bioinformatics

    JF - Bioinformatics

    SN - 1367-4803

    IS - 4

    ER -