Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.05.07.593019

Enhancing Whole Slide Image Classification with Discriminative and Contrastive Learning

Abstract

Whole slide image (WSI) classification plays a crucial role in digital pathology data analysis. However, the immense size of WSIs and the absence of fine-grained sub-region labels, such as patches, pose significant challenges for accurate WSI classification. Typical classification-driven deep learning methods often struggle to generate compact image representations, which can compromise the robustness of WSI classification. In this study, we address this challenge by incorporating both discriminative and contrastive learning techniques for WSI classification. Different from the extant contrastive learning methods for WSI classification that primarily assign pseudo labels to patches based on the WSI-level labels, our approach takes a different route to directly focus on constructing positive and negative samples at the WSI-level. Specifically, we select a subset of representative and informative patches to represent WSIs and create positive and negative samples at the WSI-level, allowing us to better capture WSI-level information and increase the likelihood of effectively learning informative features. Experimental results on two datasets and ablation studies have demonstrated that our method significantly improved the WSI classification performance compared to state-of-the-art deep learning methods and enabled learning of informative features that promoted robustness of the WSI classification.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Liang, P., Zheng, H., Li, H., Gong, Y., Fan, Y.. 2024-05-10. Enhancing Whole Slide Image Classification with Discriminative and Contrastive Learning. https://doi.org/10.1101/2024.05.07.593019

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

Bradykinin Contributes to Vasogenic Edema in Murine Experimental Cerebral Malaria

Cerebral malaria (CM) due to Plasmodium falciparum (Pf) infection is a major cause of death in African children. Bradykinin (BK) is a mediator of vasogenic edema. It could contribute to the pathogenesis of central nervous system malaria in Kenyan children and P. berghei ANKA (PbA) infected C57BL/6J mice with experimental cerebral malaria. Cleaved plasma high molecular weight kininogen (cHK) is a marker for prior BK release. 40% of children with central nervous system malaria had plasma cHK versus 18% of children with uncomplicated malaria. Wild-type PbA-infected mice had circulating plasma cHK, elevated BK levels, and reduced HK and prekallikrein levels. HK null (Kng1-/-), combined BK B1 and B2 receptor null (Bdkrb1-/- / Bdkrb2-/-), BK B2 (Bdkrb2-/-) or BK B1 (Bdkrb1-/-) receptor null mice were protected from neurologic deterioration and brain edema compared to wild-type mice. F12-/-mice were not protected from neurological deterioration. Prekallikrein null (Klkb1-/-), prolylcarboxypeptidase hypomorphs (Prcpgt/gt), and brain endothelial cell conditional knockout of PRCP (Prcpfl/fl Cre) mice had reduced neurologic deterioration and brain edema. Adjuvant plasma kallikrein inhibition combined with artesunate treatment of PbA-infected mice reversed neurologic deterioration and brain edema and prolonged survival relative to artesunate alone. BK-induced vasogenic edema contributes to human and murine CM.

pathology↗

Glutathione impacts both Batrachochytrium dendrobatidis virulence and amphibian cellular defence in a chytridiomycosis model

Glutathione has important roles in diverse infections, yet its involvement in the interaction between the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd) and its amphibian hosts is still unclear. Using in vitro assays and a cell infection model, we examined how glutathione influences Bd virulence traits and cellular host disease resistance. For Bd, inhibition of glutathione reductase rapidly killed zoospores, indicating that glutathione is essential for this pathogen. In addition, exposure to exogenous glutathione promoted the potential for virulence through accelerated and increased zoospore release. In host amphibian cells, Bd infection decreased intracellular glutathione content and increased reactive oxygen species, suggesting that chytridiomycosis pathogenesis may involve oxidative stress. Depletion of host glutathione before exposure to Bd increased infection severity and Bd growth, whereas amphibian cells with slightly elevated glutathione levels were partially protected against Bd. However, manipulation of host glutathione levels after the establishment of Bd infection did not impact its intracellular growth, implying that the host glutathione-mediated resistance only occurs during the initial Bd invasion process. Importantly, this effect of glutathione on host resistance is not a general response to pathogens, as it was not observed in cells exposed to viral pathogen FV3. As glutathione increased both infectious zoospore production and host resistance to zoospore infection, our study suggests that this antioxidant may play an important role in the host/pathogen interaction during chytridiomycosis. Thus, environmental conditions and therapeutic approaches that affect glutathione systems in the host and/or pathogen have the potential to alter chytridiomycosis dynamics and should be further explored.

pathology↗