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A Pan-Cancer PDX Histology Image Repository with Genomic and Pathological Annotations for Deep Learning Analysis

Cancer research(2023)

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摘要
Patient-derived xenografts (PDXs) model human intra-tumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histological imaging via hematoxylin and eosin (H&E) staining is performed on PDX samples for routine assessment and, in principle, captures the complex interplay between tumor and stromal cells. Deep learning (DL)-based analysis of large human H&E image repositories has extracted inter-cellular and morphological signals correlated with disease phenotype and therapeutic response. Here, we present an extensive, pan-cancer repository of nearly 1,000 PDX and paired human progenitor H&E images. These images, curated from the PDXNet consortium, are associated with genomic and transcriptomic data, clinical metadata, pathological assessment of cell composition, and, in several cases, detailed pathological annotation of tumor, stroma, and necrotic regions. We demonstrate that DL can be applied to these images to classify tumor regions and to predict xenograft-transplant lymphoproliferative disorder, the unintended outgrowth of human lymphocytes at the transplantation site. This repository enables PDX-specific, investigations of cancer biology through histopathological analysis and contributes important model system data that expand on existing human histology repositories. We expect the PDXNet Image Repository to be valuable for controlled digital pathology analysis, both for the evaluation of technical issues such as stain normalization and for development of novel computational methods based on spatial behaviors within cancer tissues.### Competing Interest StatementThe University of Utah may choose to license PDX models developed in the Welm labs, which may result in tangible property royalties to Dr Welm and members of their lab who developed the models. Michael T. Lewis is a founder and limited partner in StemMed Ltd. and a manager in StemMed Holdings, it's general partner. He is a founder and equity stake holder in Tvardi Therapeutics Inc. Some PDX are exclusively licensed to StemMed Ltd. resulting in royalty income to MTL. Lacey Dobrolecki is a compensated employee of StemMed Ltd. The other authors declare no competing interest.
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