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Browsing by Subject "Histopathological images"
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Item A deep learning framework for automated classification of histopathological kidney whole-slide images(Elsevier, 2022-04-18) Abdeltawab, Hisham A.; Khalifa, Fahmi A.; Ghazal, Mohammed A.; Cheng, Liang; El-Baz, Ayman S.; Gondim, Dibson D.; Pathology and Laboratory Medicine, School of MedicineBackground: Renal cell carcinoma is the most common type of malignant kidney tumor and is responsible for 14,830 deaths per year in the United States. Among the four most common subtypes of renal cell carcinoma, clear cell renal cell carcinoma has the worst prognosis and clear cell papillary renal cell carcinoma appears to have no malignant potential. Distinction between these two subtypes can be difficult due to morphologic overlap on examination of histopathological preparation stained with hematoxylin and eosin. Ancillary techniques, such as immunohistochemistry, can be helpful, but they are not universally available. We propose and evaluate a new deep learning framework for tumor classification tasks to distinguish clear cell renal cell carcinoma from papillary renal cell carcinoma. Methods: Our deep learning framework is composed of three convolutional neural networks. We divided whole-slide kidney images into patches with three different sizes where each network processes a specific patch size. Our framework provides patchwise and pixelwise classification. The histopathological kidney data is composed of 64 image slides that belong to 4 categories: fat, parenchyma, clear cell renal cell carcinoma, and clear cell papillary renal cell carcinoma. The final output of our framework is an image map where each pixel is classified into one class. To maintain consistency, we processed the map with Gauss-Markov random field smoothing. Results: Our framework succeeded in classifying the four classes and showed superior performance compared to well-established state-of-the-art methods (pixel accuracy: 0.89 ResNet18, 0.92 proposed). Conclusions: Deep learning techniques have a significant potential for cancer diagnosis.Item Integrative analysis of histopathological images and chromatin accessibility data for estrogen receptor-positive breast cancer(BMC, 2020-12-28) Xu, Siwen; Lu, Zixiao; Shao, Wei; Yu, Christina Y.; Reiter, Jill L.; Feng, Qianjin; Feng, Weixing; Huang, Kun; Liu, Yunlong; Medicine, School of MedicineBackground: Existing studies have demonstrated that the integrative analysis of histopathological images and genomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, since the development of pathological phenotypes are influenced by a variety of complex biological processes, complete understanding of the underlying gene regulatory mechanisms for the cell and tissue morphology is still a challenge. In this study, we explored the relationship between the chromatin accessibility changes and the epithelial tissue proportion in histopathological images of estrogen receptor (ER) positive breast cancer. Methods: An established whole slide image processing pipeline based on deep learning was used to perform global segmentation of epithelial and stromal tissues. We then used canonical correlation analysis to detect the epithelial tissue proportion-associated regulatory regions. By integrating ATAC-seq data with matched RNA-seq data, we found the potential target genes that associated with these regulatory regions. Then we used these genes to perform the following pathway and survival analysis. Results: Using canonical correlation analysis, we detected 436 potential regulatory regions that exhibited significant correlation between quantitative chromatin accessibility changes and the epithelial tissue proportion in tumors from 54 patients (FDR < 0.05). We then found that these 436 regulatory regions were associated with 74 potential target genes. After functional enrichment analysis, we observed that these potential target genes were enriched in cancer-associated pathways. We further demonstrated that using the gene expression signals and the epithelial tissue proportion extracted from this integration framework could stratify patient prognoses more accurately, outperforming predictions based on only omics or image features. Conclusion: This integrative analysis is a useful strategy for identifying potential regulatory regions in the human genome that are associated with tumor tissue quantification. This study will enable efficient prioritization of genomic regulatory regions identified by ATAC-seq data for further studies to validate their causal regulatory function. Ultimately, identifying epithelial tissue proportion-associated regulatory regions will further our understanding of the underlying molecular mechanisms of disease and inform the development of potential therapeutic targets.Item Spatial Transcriptomic Analysis Reveals Associations between Genes and Cellular Topology in Breast and Prostate Cancers(MDPI, 2022-10-04) Alsaleh, Lujain; Li, Chen; Couetil, Justin L.; Ye, Ze; Huang, Kun; Zhang, Jie; Chen, Chao; Johnson, Travis S.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Cancer is the leading cause of death worldwide with breast and prostate cancer the most common among women and men, respectively. Gene expression and image features are independently prognostic of patient survival; but until the advent of spatial transcriptomics (ST), it was not possible to determine how gene expression of cells was tied to their spatial relationships (i.e., topology). Methods: We identify topology-associated genes (TAGs) that correlate with 700 image topological features (ITFs) in breast and prostate cancer ST samples. Genes and image topological features are independently clustered and correlated with each other. Themes among genes correlated with ITFs are investigated by functional enrichment analysis. Results: Overall, topology-associated genes (TAG) corresponding to extracellular matrix (ECM) and Collagen Type I Trimer gene ontology terms are common to both prostate and breast cancer. In breast cancer specifically, we identify the ZAG-PIP Complex as a TAG. In prostate cancer, we identify distinct TAGs that are enriched for GI dysmotility and the IgA immunoglobulin complex. We identified TAGs in every ST slide regardless of cancer type. Conclusions: These TAGs are enriched for ontology terms, illustrating the biological relevance to our image topology features and their potential utility in diagnostic and prognostic models.