Deep models of integrated multiscale molecular data decipher the endothelial cell response to ionizing radiation

综合多尺度分子数据的深度模型解读内皮细胞对电离辐射的反应

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作者:Ian Morilla, Philippe Chan, Fanny Caffin, Ljubica Svilar, Sonia Selbonne, Ségolène Ladaigue, Valérie Buard, Georges Tarlet, Béatrice Micheau, Vincent Paget, Agnès François, Maâmar Souidi, Jean-Charles Martin, David Vaudry, Mohamed-Amine Benadjaoud, Fabien Milliat, Olivier Guipaud

Abstract

The vascular endothelium is a hot spot in the response to radiation therapy for both tumors and normal tissues. To improve patient outcomes, interpretable systemic hypotheses are needed to help radiobiologists and radiation oncologists propose endothelial targets that could protect normal tissues from the adverse effects of radiation therapy and/or enhance its antitumor potential. To this end, we captured the kinetics of multi-omics layers-i.e. miRNome, targeted transcriptome, proteome, and metabolome-in irradiated primary human endothelial cells cultured in vitro. We then designed a strategy of deep learning as in convolutional graph networks that facilitates unsupervised high-level feature extraction of important omics data to learn how ionizing radiation-induced endothelial dysfunction may evolve over time. Last, we present experimental data showing that some of the features identified using our approach are involved in the alteration of angiogenesis by ionizing radiation.

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