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Traducir el transcriptoma: un enfoque de conectomía para el mapeo de redes genéticas y la aplicación clínica

Clemens Neudorfer ^1,2,3, Bassam Al-Fatly ³, Barbara Hollunder ^3,4,5

¹Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
³Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴Einstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁵Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
⁶Department of Neurology, Tufts Medical Center, Boston, MA, USA.
⁷Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
⁸Neurosciences Queensland, St. Andrew's War Memorial Hospital, Spring Hill, Queensland, Australia.
⁹Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, Queensland, Australia.
¹⁰Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation Health and Biosecurity, Herston, Queensland, Australia.
¹¹Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom.
¹²National Hospital for Neurology and Neurosurgery, University College London Queen Square Institute of Neurology, London, United Kingdom.
¹³Centre for Mental Health, Swinburne University of Melbourne, Victoria, Australia.
¹⁴St. Vincent's Hospital, Melbourne, Victoria, Australia.
¹⁵Department of Psychiatry, University of Melbourne, Melbourne, Australia.
¹⁶Movement Disorders and Neuromodulation Centre, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
¹⁷Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
¹⁸Department of Neurology, Amsterdam University Medical Center, Amsterdam, Netherlands.
¹⁹Department of Neurosurgery, Hospital Clínico San Carlos, Instituto de Investigacion Sanitaria San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
²⁰Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
²¹Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
²²Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²³Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York.
²⁴Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
²⁵Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
²⁶Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²⁷Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, VIC, Australia.
²⁸Turku Brain and Mind Center, University of Turku, Turku, Finland.
²⁹Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
³⁰Cluster of Excellence Matters of Activity. Image Space Material, Humboldt-Universität zu Berlin, Berlin, Germany.
³¹Department of Neurology, Toronto Western Hospital, Toronto, Canada.
³²Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³³Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁴Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³⁵Institute of Neurogenetics, University of Lubeck, Lubeck, Germany.

⁰Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Medrxiv : the Preprint Server for Health Sciences +

|

20 de agosto de 2025

Ver abstracta en PubMed

Resumen

Este estudio introduce el mapeo de redes de genes para vincular la expresión génica con las redes cerebrales. Los mapas de redes de enfermedades revelan efectos genéticos acumulativos, lo que ayuda a la medicina de precisión para los trastornos cerebrales.

Área De La Ciencia

La neurociencia
La genética
Biología computacional

Sus Antecedentes

La expresión génica influye en la conectividad funcional del cerebro, pero las redes genéticas compartidas en los trastornos siguen sin estar claras.
Comprender las bases moleculares de los trastornos cerebrales es crucial para desarrollar terapias dirigidas.

Objetivo Del Estudio

Desarrollar un marco, mapeo de redes de genes, para identificar las redes cerebrales asociadas con la expresión génica.
Para crear mapas de redes de enfermedades que representan el impacto genético acumulado en los circuitos cerebrales.
Validar estos mapas utilizando conjuntos de datos independientes y evaluar su relevancia clínica.

Principales Métodos

Transcriptómica espacial combinada con datos normativos de conectividad funcional.
Generó mapas de redes de genes para genes individuales y los agregó en mapas de redes de enfermedades.
Mapas validados con datos de lesiones y resultados de estimulación cerebral profunda (DBS).

Principales Resultados

El mapeo de la red de genes identificó con éxito patrones de conectividad distribuidos para genes individuales.
Los mapas de redes de enfermedades capturaron la influencia genética acumulada en las redes cerebrales.
La modulación de la red predijo resultados en cohortes de estimulación cerebral profunda, validando los mapas.

Conclusiones

El mapeo de la red de genes proporciona una herramienta novedosa para explorar la arquitectura molecular de los trastornos cerebrales.
Este marco apoya el diagnóstico y la terapéutica basados en redes en la medicina de precisión.
El estudio destaca la convergencia de genes en redes cerebrales compartidas en el contexto de la enfermedad.

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