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Updated: Jun 27, 2026

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
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Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

Zhang-Zhi Hu1, Hongzhan Huang, Amrita Cheema

  • 1Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.

Journal of Proteomics & Bioinformatics
|December 18, 2008
PubMed
Summary
This summary is machine-generated.

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Ionizing radiation impacts cellular metabolism in an ATM-dependent manner. Researchers identified ribonucleoside-diphosphate reductase subunit M2 (RRM2) as a key downstream target in DNA repair via the ATM-p53 pathway.

Area of Science:

  • Molecular Biology
  • Genetics
  • Bioinformatics

Background:

  • Large-scale omics data analysis requires integrated bioinformatics tools.
  • Ataxia-telangiectasia mutated (ATM) kinase is crucial for cellular response to DNA damage.
  • Understanding ATM's role in radiation response is vital for DNA repair mechanisms.

Purpose of the Study:

  • To analyze cellular pathways affected by ionizing radiation using an integrated bioinformatics approach.
  • To investigate the role of ATM in radiation-induced metabolic changes.
  • To identify downstream targets of the ATM pathway involved in DNA repair.

Main Methods:

  • Utilized a 2D-gel/MS proteomics and microarray gene expression analysis.
  • Compared gene and protein expression in fibroblasts with wild-type versus mutant ATM.

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  • Applied integrated bioinformatics tools for pathway and target identification.

    • Main Results:

    • Metabolism was significantly altered by radiation in an ATM-dependent manner.
    • Purine metabolic pathways showed differential changes between ATM wild-type and mutant cells.
    • Ribonucleoside-diphosphate reductase subunit M2 (RRM2) expression increased in ATM wild-type cells post-irradiation, unlike in ATM-mutated cells.

    Conclusions:

    • RRM2 is a downstream target of the ATM-p53 pathway involved in radiation-induced DNA repair.
    • Integrated bioinformatics approaches are effective for pathway analysis and target discovery.
    • ATM status critically influences cellular metabolic response to ionizing radiation.