Inter-Individual Variation in DNA Repair Capacity

Standardizing statistical approach to apply novel DNA repair assay in population studies.

Project Overview

This project aims to standardize analytical approaches for applying a novel DNA repair assay (FM-HCR) to population-level studies and provide a comprehensive measurement of inter-individual variation in DNA repair capacity. By leveraging high-throughput functional assays of DNA repair with a standardized analytical pipeline and user-friendly website, our study seeks to establish best practices for population-based DNA repair capacity measurements in precision medicine.

Objectives

  • Develop and validate a standardized pipeline for population-scale DNA repair capacity assays.
  • Identify inter-individual variability in repair mechanisms using high-throughput analysis.
  • Develop an R package and an interactive web-based platform for broader research applications.

Methodology

This study employs a combination of:

  • Multiplex functional DNA repair assays to simultaneously measure major pathway DNA repair capacity in human peripheral mononuclear blood cells.
  • Development of an R package (pdrc) and website interface for analyzing DNA repair capacity data on populuation scale.
  • Advanced statistical modeling to quantify inter-individual differences in healthy volunteers.

Tools

  • R package (pdrc): See GitHub repository here.
  • Shiny-based website: Interactive tool for analyzing DNA repair capacity here.

Manuscript in Preparation

  • Title: Comprehensive Measurement of Inter-Individual Variation in DNA Repair Capacity
  • Target Submission Date: Spring 2025
  • Key Contributions: First comprehensive functional assessment of DNA repair variation across individuals.

Visual Highlights - available soon

Visualizing the study: (Left) Study workflow, (Middle) DNA repair landscape, (Right) Correlations among the pathways.

Next Steps

  • Expand cohort analysis to confirm findings across larger populations.
  • Enhance the web-based platform with additional functionalities for researchers.

References & Related Work

  • FM-HCR: a powerful method to quantify multiple DNA repair pathways in living cells, originally developed by Dr. Zachary Nagel in a pair of articles (PNAS 2014, PNAS 2017).
  • CometChip: a high-throughput comet assay allowing parallel quantification of multiple DNA repair activities (PNAS 2010).
  • Prior work: DNA repair activities were measured by CometChip in 56 healthy individuals (Free Radical Biology and Medicine 2021).

For further inquiries, feel free to reach out!