Effects of low dose ionizing radiation on DNA damage-caused pathways by reverse-phase protein array and Bayesian...

Area of Science:

• Molecular Biology
• Genomics
• Biophysics

Background:

• Ionizing radiation (IR) induces DNA damage, triggering cellular responses including DNA repair, cell cycle control, and apoptosis.
• Understanding these responses is crucial for assessing the biological impact of radiation exposure.

Purpose of the Study:

• To investigate the effects of low dose IR on human cellular signaling pathways.
• To identify proteins involved in DNA damage response pathways using the Ataxia Telangiectasia mutated (ATM) pathway as a focus.

Main Methods:

• Utilized Reverse-Phase Protein Array (RPPA) and isogenic human Ataxia Telangiectasia (A-T) cells.
• Employed correlation coefficient analysis to select interacting proteins under IR.
• Inferred signaling pathways using Bayesian networks integrated with Protein-Protein Interactions (PPIs) and Dempster-Shafer theory (DST).

Main Results:

• Identified specific proteins involved in cellular signaling pathways under IR exposure.
• Demonstrated differences in inferred pathways between low and high dose IR.
• Characterized the regulatory interactions among selected proteins within these pathways.

Conclusions:

• Low dose IR induces DNA damage and affects key signaling pathways, including apoptosis, cell cycle regulation, and DNA repair.
• The study provides insights into the molecular mechanisms underlying cellular responses to IR.