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Biology subjects

Vickery, J. M.

Publications and source records attributed to Vickery, J. M..

2 recordsLinked to original sources

Generative Adversarial Networks Accurately Reconstruct Pan-Cancer Histology from Pathologic, Genomic, and Radiographic Latent Features

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network - HistoXGAN - capable of reconstructing representative histology using feature vectors produced by common feature extractors. We evaluate HistoXGAN across 29 cancer subtypes and demonstrate that reconstructed images retain information regarding tumor grade, histologic subtype, and gene expression patterns. We leverage HistoXGAN to illustrate the underlying histologic features for deep learning models for actionable mutations, identify model reliance on histologic batch effect in predictions, and demonstrate accurate reconstruction of tumor histology from radiographic imaging for a virtual biopsy.

cancer biology↗

Synaptopodin is necessary for Shigella flexneri intercellular spread

For many intracellular pathogens, their virulence depends on an ability to spread between cells of an epithelial layer. For intercellular spread to occur, these pathogens deform the plasma membrane into a protrusion structure that is engulfed by the neighboring cell. Although the polymerization of actin is essential for spread, how these pathogens manipulate the actin cytoskeleton in a manner that enables protrusion formation is still incompletely understood. Here, we show that butyrate responsive pathways promote intercellular spread by Shigella flexneri. We identify the mammalian actin binding protein synaptopodin, a butyrate responsive gene, as required for efficient intercellular spread of S. flexneri and Listeria monocytogenes. We show synaptopodin enhances the recruitment of actin to bacteria and stabilizes the actin tail. We show that, for S. flexneri, synaptopodin presence enables protrusions to form and to resolve at a greater rate, indicating that greater stability of the actin tail enables the bacteria to push against the membrane with greater force. We demonstrate that synaptopodin recruitment around bacteria requires the bacterial protein IcsA, and we show that this recruitment is further enhanced in a type 3 secretion system dependent manner. These data establish synaptopodin as required for intracellular bacteria to stabilize the actin cytoskeleton in a manner that enables efficient protrusion formation and identify for the first time that synaptopodin contributes to bacterial pathogenesis.

microbiology↗