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Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits

2023; Cell Press; Volume: 41; Issue: 9 Linguagem: Inglês

10.1016/j.ccell.2023.07.010

1878-3686

Alberto Sánchez-Aguilera, Mariam Masmudi‐Martín, Andrea Navas-Olivé, Patricia Baena, Carolina Hernández-Oliver, Neibla Priego, Lluís Cordón-Barris, Laura Álvaro‐Espinosa, Santiago García‐Martín, Sonia Martı́nez, Miguel Lafarga, Michael Z. Lin, Fátima Al‐Shahrour, Liset Menéndez de la Prida, Manuel Valiente, Cecilia Sobrino, Nuria Ajenjo, María-Jesús Artiga, Eva Ortega‐Paino, Virginia García-Calvo, Ángel Pérez‐Núñez, P. González, Luis Jiménez‐Roldán, Luis Miguel García Moreno, Olga Esteban, Juan Manuel Sepúlveda-Sánchez, Óscar Toldos, Aurelio Hernández-Laín, Alicia Arenas, Guillermo Blasco, J.F. Alén, Adolfo de la Lama Zaragoza, Antía Domínguez Núñez, Lourdes Calero, Concepción Fiaño Valverde, Ana González Piñeiro, Pedro David Delgado‐López, Mar Pascual, Gerard Plans Ahicart, Begoña Escolano Otín,

Glioma Diagnosis and Treatment

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.