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Mapeo de isoformas y mecanismos reguladores a partir de datos de transcriptómica espacial con SPLISOSM

Jiayu Su1,2,3, Yiming Qu4, Megan Schertzer5

  • 1Program for Mathematical Genomics, Columbia University, New York, NY, USA. js5756@cumc.columbia.edu.

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|January 6, 2026
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Resumen
Este resumen es generado por máquina.

Desarrollamos SPLISOSM para mapear la diversidad transcripcional en datos de transcriptómica espacial. Este método revela miles de eventos de empalme espacialmente variables en el cerebro, vinculados a trastornos neuropsiquiátricos y cáncer.

Palabras clave:
transcriptómica espacialisoformasempalmemodelado estadísticogenómicaneurocienciabiología computacional

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Área de la Ciencia:

  • Genómica
  • Neurociencia
  • Biología Computacional

Sus antecedentes:

  • La diversidad transcripcional, incluido el empalme y el uso alternativo del extremo 3', es vital para la función celular, pero su regulación espacial no está clara.
  • La transcriptómica espacial ofrece una forma de estudiar la expresión génica en su contexto tisular.

Objetivo del estudio:

  • Desarrollar un método para detectar patrones a resolución de isoformas en datos de transcriptómica espacial.
  • Analizar la diversidad transcripcional espacial en el cerebro de ratón y humano en condiciones normales y neoplásicas.

Principales métodos:

  • Introdujo SPLISOSM (modelado estadístico de isoformas espaciales), un método que utiliza pruebas multivariadas con núcleos no paramétricos.
  • Aplicó SPLISOSM a datos de transcriptómica espacial de muestras de cerebro de ratón y humano, incluido el glioblastoma.

Principales resultados:

  • Identificó más de 1000 eventos de diversidad transcripcional espacialmente variables en el cerebro de ratón, enriquecidos en vías de señalización sináptica relacionadas con trastornos neuropsiquiátricos.
  • Descubrió patrones de empalme espacial conservados entre la corteza prefrontal de ratón y humana.
  • Reveló una diversidad transcripcional generalizada en el glioblastoma humano, asociada con genes de presentación de antígenos y adhesión y microambientes específicos.

Conclusiones:

  • SPLISOSM permite un análisis estadístico potente de la diversidad transcripcional espacial incluso con datos escasos.
  • La diversidad transcripcional espacial juega un papel importante en la función cerebral, los trastornos neuropsiquiátricos y el cáncer.
  • Este estudio proporciona un análisis integral del empalme espacial del cerebro en la salud y la enfermedad.