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Characterization of Continuous Transcriptional Heterogeneity in High-Risk Blastemal-Type Wilms' Tumors Using Unsupervised Machine Learning.
Trink, Yaron; Urbach, Achia; Dekel, Benjamin; Hohenstein, Peter; Goldberger, Jacob; Kalisky, Tomer.
Afiliación
  • Trink Y; Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan 5290002, Israel.
  • Urbach A; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
  • Dekel B; Pediatric Stem Cell Research Institute and Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 5262000, Israel.
  • Hohenstein P; Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
  • Goldberger J; Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan 5290002, Israel.
  • Kalisky T; Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan 5290002, Israel.
Int J Mol Sci ; 24(4)2023 Feb 09.
Article en En | MEDLINE | ID: mdl-36834944
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 generative probabilistic "grade of membership" model, we show that each tumor can be represented as a unique mixture of three hidden "topics" with blastemal, stromal, and epithelial characteristics. Likewise, cellular deconvolution allows us to represent each tumor in the continuum as a unique combination of fetal kidney-like cell states. These results highlight the relationship between Wilms' tumors and kidney development, and we anticipate that they will pave the way for more quantitative strategies for tumor stratification and classification.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor de Wilms / Neoplasias Renales Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor de Wilms / Neoplasias Renales Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza