Our overarching goal is to develop the capabilities to assess individual tissue specific response from low dose radiation using quantitative proteomics data from plasma extracellular vesicles (EVs). We will generate a quantitative proteomics dataset that will measure individual tissue responses to low dose radiation in a mouse model. Using a custom modified Xstrahl Small Animal Radiation Research Platform (SARRP), capable of delivering 5 mGy/hr dose rate, we will expose cohorts of mice to varying low doses of X-ray irradiation (0-100 mGy). We will generate untargeted proteomic datasets from multiple mouse tissues and plasma EVs using data independent acquisition (DIA) on an Orbitrap Astral mass spectrometer.  Additionally, low abundance DNA damage response (DDR) proteins and their modifications will be targeted using the new Stellar linear ion trap mass spectrometer, specifically designed for highly multiplexed, ultrasensitive targeted analysis. We will analyze the proteome of plasma EVs as a “liquid biopsy” and train a machine learning model using the systemic EV measurement to predict X-ray dose and tissue-specific protein perturbations, including DNA damage response.