Characterization of Continuous Transcriptional Heterogeneity in High-Risk Blastemal-Type Wilms' Tumors Using Unsupervised Machine Learning.

ABSTRACT: Wilms' tumors are pediatric malignancies that are thought to arise from faulty kidney development. They contain a wide range of poorly differentiated cell states resembling various distorted developmental stages of the fetal kidney, and as a result, differ between patients in a continuous manner that is not well understood. Here, we used three computational approaches to characterize this continuous heterogeneity in high-risk blastemal-type Wilms' tumors. Using Pareto task inference, we show that the tumors form a triangle-shaped continuum in latent space that is bounded by three tumor archetypes with "stromal", "blastemal", and "epithelial" characteristics, which resemble the un-induced mesenchyme, the cap mesenchyme, and early epithelial structures of the fetal kidney. By fitting a gener

SUBMITTER: Trink Y 

PROVIDER: S-EPMC9965420 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature