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|Abstract:||Histopathological images are used to characterize complex phenotypes such as tumor stage. Our goal is to associate features of stained tissue images with high-dimensional genomic markers. We use convolutional autoencoders and sparse canonical correlation analysis (CCA) on paired histological images and bulk gene expression to identify subsets of genes whose expression levels in a tissue sample correlate with subsets of morphological features from the corresponding sample image. We apply our approach, ImageCCA, to two TCGA data sets, and find gene sets associated with the structure of the extracellular matrix and cell wall infrastructure, implicating uncharacterized genes in extracellular processes. We find sets of genes associated with specific cell types, including neuronal cells and cells of the immune system. We apply ImageCCA to the GTEx v6 data, and find image features that capture population variation in thyroid and in colon tissues associated with genetic variants (image morphology QTLs, or imQTLs), suggesting that genetic variation regulates population variation in tissue morphological traits.|
|Citation:||Ash, Jordan T., Gregory Darnell, Daniel Munro, and Barbara E. Engelhardt. "Joint analysis of expression levels and histological images identifies genes associated with tissue morphology." Nature Communications 12, no. 1 (2021). doi:10.1038/s41467-021-21727-x|
|Type of Material:||Journal Article|
|Journal/Proceeding Title:||Nature Communications|
|Version:||Final published version. This is an open access article.|
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