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Dynamics of cellular level function and regulation derived from murine expression array data.

Benjamin de Bivort1, Sui Huang, Yaneer Bar-Yam

  • 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. bivort@fas.harvard.edu

Proceedings of the National Academy of Sciences of the United States of America
|December 16, 2004
PubMed
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Systems biology research reveals how gene groups influence cellular functions. Large-scale analysis identified key regulatory dynamics, including energy metabolism and cell-cycle control, in murine B lymphocytes.

Area of Science:

  • Systems biology
  • Molecular biology
  • Bioinformatics

Background:

  • Understanding gene and molecular interactions in cellular phenotypes is a key challenge.
  • Previous efforts focused on small gene networks, limiting insights into cellular-level function.
  • Microarray bioinformatics has not been fully utilized for cellular-level functional influence determination.

Purpose of the Study:

  • To analyze large-scale gene interactions for cellular-level function dynamics.
  • To identify effective aggregate regulatory influences among major gene groups.
  • To investigate cellular behavior at a high level of abstraction using gene megamodules.

Main Methods:

  • Aggregated genes into "megamodules" based on related behaviors.
  • Utilized microarray bioinformatics for large-scale data analysis.

Related Experiment Videos

  • Determined effective aggregate regulatory influences among 12 major gene groups in murine B lymphocytes over time.

    • Main Results:

    • Identified medium-term dependence on mitochondrial ATP-generating genes.
    • Observed longer-term dependence on glycolytic genes.
    • Found chromatin-reorganizing genes have dual roles (activation/repression).
    • Detected homeostasis-favoring influences.
    • Indicated G protein-mediated signals are not concentration-dependent.
    • Revealed cell-cycle system exhibits short-term activation/long-term repression.

    Conclusions:

    • Large-scale gene interaction analysis provides insights into cellular dynamics.
    • Energy metabolism (mitochondrial and glycolytic) plays critical roles in cellular function over different timescales.
    • Chromatin remodeling and signaling pathways exhibit complex regulatory behaviors.
    • Cellular systems like the cell cycle display distinct temporal regulatory patterns.