Video Experimental Relacionado

Updated: Jan 7, 2026

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

Módulos funcionales predicen interacciones genéticas relevantes para el cáncer en células de mamíferos

Chenchu Lin¹, Veronica Gheorghe¹, Juihsuan Chou^1,2

¹Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

bioRxiv : the preprint server for biology

|December 25, 2025

Abstract:

Genetic interactions can reveal gene function and identify cancer-relevant synthetic lethals, but systematic mapping in human cells is constrained by inefficient reagents, vast combinatorial search space, and diversity of cell types. Here, we leverage principles from yeast genetic networks to identify human gene modules enriched for genetic interactions. Using our Cas12a-based In4mer combinatorial knockout platform, we screen all pairwise interactions within receptor tyrosine kinase and DNA damage response modules across eight diverse cancer cell lines. We identify hundreds of unreported synthetic lethals, including a dense network within the protein glycosylation machinery, and confirm that interactions in 2D cell culture are maintained in more physiologically relevant models. Our targeted modules show up to 16-fold enrichment of interaction density, providing a scalable strategy for systematic interaction mapping.

Palabras clave:

interacciones genéticas letalidad sintética glicosilación de proteínas mapeo genético descubrimiento de fármacos cáncer células humanas Cas12a módulos genéticos respuesta al daño del ADN

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