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Saleeb, R.

Publications and source records attributed to Saleeb, R..

2 recordsLinked to original sources

PHARAOH: A collaborative crowdsourcing platform for PHenotyping And Regional Analysis Of Histology

Deep learning has proven to be capable of automating key aspects of histopathologic analysis, but its continual reliance on large expert-annotated training datasets hinders widespread adoption. Here, we present an online collaborative portal that streamlines tissue image annotation to promote the development and sharing of custom computer vision models for PHenotyping And Regional Analysis Of Histology (PHARAOH; https://www.pathologyreports.ai/). PHARAOH uses a weakly supervised active learning framework whereby patch-level image features are leveraged to organize large swaths of tissue into morphologically-uniform clusters for batched human annotation. By providing cluster-level labels on only a handful of cases, we show how custom PHARAOH models can be developed and used to guide the quantification of cellular features that correlate with molecular, pathologic and patient outcome data. Both custom model design and feature extraction pipelines are amenable to crowdsourcing making PHARAOH a fully scalable systems-level solution for the systematic expansion and cataloging of computational pathology applications.

bioinformatics↗

Myocardin-related transcription factor drives epithelial fibrogenesis in polycystic kidney disease

Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby the loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in cystogenesis, and we have shown that the RhoA/cytoskeleton/myocardin-related transcription factor (MRTF) pathway is a key mediator of epithelium-induced fibrogenesis. Therefore, we hypothesized that MRTF is activated by PC1/2 loss and plays a critical role in fibrogenic reprogramming of the epithelium. Loss of PC1 or PC2 induced by siRNA in vitro activated RhoA, caused cytoskeletal remodeling and robust nuclear MRTF translocation and overexpression. These phenomena were also manifest in PKD1 (RC/RC) and PKD2 (WS25/-) mice, with MRTF translocation and overexpression occurring predominantly in dilated tubules and in cyst-lining epithelium, respectively. In epithelial cells, a large cohort of PC1/PC2 downregulation-induced genes was MRTF-dependent, including cytoskeletal, integrin-related, and matricellular/fibrogenic proteins. Epithelial MRTF was necessary for paracrine priming of fibroblast-myofibroblast transition. Thus, MRTF is a critical novel mediator of the PC1/2 loss-induced profibrotic epithelial phenotype, and consequently PKD-related fibrosis.

cell biology↗