Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21727-x
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Funding
- NIH [R01 HL133218]
- Sloan Faculty Fellowship
- NSF CAREER [AWD1005627]
- NSF Graduate Research Fellowship Program [DGE 1148900]
- CZI [AWD1005664, AWD1005667]
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The study aims to associate features of stained tissue images with high-dimensional genomic markers, identifying gene sets related to cell types and extracellular structures, and exploring how genetic variation regulates population variation in tissue morphological traits.
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.
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