RENEB Inter-Laboratory Comparison 2021: The Gene Expression Assay.

Area of Science:

• Radiation biology and dosimetry
• Molecular epidemiology
• Genomics and transcriptomics

Background:

• Accurate and rapid individual dose estimation is critical for managing large-scale radiation exposure events.
• Gene expression profiling offers a promising avenue for biodosimetry, enabling timely assessment of radiation doses.

Purpose of the Study:

• To evaluate the performance of gene expression assays for dose estimation in a simulated radiation exposure scenario.
• To compare the accuracy and efficiency of different gene expression-based biodosimetry approaches.
• To assess the utility of gene expression for classifying individuals into clinically relevant dose categories.

Main Methods:

• Eight laboratories participated in an inter-laboratory exercise using whole blood samples exposed to 0, 1.2, and 3.5 Gy X-rays.
• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses were employed for gene expression measurements.
• Dose estimates were calculated, and accuracy was assessed using summed absolute difference (SAD) and correct classification into dose categories.

Main Results:

• Gene expression assays provided dose estimates within hours, confirming early and high-throughput capabilities.
• Using a combination of genes resulted in approximately two-fold lower median SADs compared to single-gene approaches.
• All teams correctly ordered dose estimates, and unexposed/highly exposed samples were accurately identified; however, low-dose samples were sometimes misclassified.

Conclusions:

• Gene expression biodosimetry is effective for rapid dose assessment and classification in radiological scenarios.
• Combining multiple genes enhances dose estimation accuracy, supporting triage and medical management decisions.
• This exercise identified technical improvements for future radiation biodosimetry efforts.