Transcriptomic decoding of surface-based imaging phenotypes and its application to pharmacotranscriptomics
Year: 2025
Type: article
Abstract: Imaging transcriptomics has become a power tool for linking imaging-derived phenotypes (IDPs) to genomic mechanisms. Yet, its potential for guiding CNS drug discovery remains underexplored. Here, utilizing spatially-dense representations of the human brain transcriptome, we present an analytical framework for the transcriptomic decoding of high-resolution surface-based neuroimaging patterns, and for linking IDPs to the transcriptomic landscape of complex neurotransmission systems in vivo. Leveraging publicly available Positron Emission Tomography (PET) data, we initially validated our approach against molecular targets with a high correspondence between gene expression and protein binding. Subsequently, we used the cortical gene expression profiles of candidate genes to dissect two discrete classes of GABA A -receptor subunits, each characterized by a distinct cortical expression pattern, and to link these to specific behavioural symptoms and traits. Our approach thus represents a future avenue for in vivo pharmacotranscriptomics that may guide the development of targeted pharmacotherapies and personalized interventions.
Source: Nature Communications
Authors: Christine Ecker, Charlotte M. Pretzsch, Johanna Leyhausen, Lisa M. Berg, Caroline Gurr, Hanna Seelemeyer, Grainne McAlonan, Nicolaas A. Puts, Eva Loth, Flavio Dell’Aqua, Luke Mason, Tony Charman, Bethany Oakley, Thomas Bourgeron, Christian Beckmann, Jan K. Buitelaar, Celso Arango, Tobias Banaschewski, Andreas G. Chiocchetti, Christine M. Freitag, Elke Hattingen, Dilja Krueger-Burg, Michael J. Schmeisser, Jonathan Repple, Andreas Reif, Declan G. Murphy
Institutions: Goethe University Frankfurt, King's College London, University Hospital Frankfurt, Institut Pasteur, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Universidad Complutense de Madrid, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Heidelberg University, Central Institute of Mental Health, Medizinische Fakultät Mannheim, Deutsches Zentrum für Psychische Gesundheit, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, University of Münster, Fraunhofer Institute for Translational Medicine and Pharmacology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Autism Speaks, European Federation of Pharmaceutical Industries and Associations, Government of the United Kingdom, UK Research and Innovation, Simons Foundation Autism Research Initiative, National Institute for Health and Care Research, European Commission, Deutsche Forschungsgemeinschaft, HORIZON EUROPE Framework Programme, NIHR Maudsley Biomedical Research Centre, Medical Research Council
Awards: G236063110, Risk and Resilience in Developmental Diversity and Mental Health, G434337789, G4345436876, G452649895, European Autism Interventions - A Multicentre Study for Developing New Medications, G5543596241, G60524263, Autism Innovative Medicine Studies – 2 – Trials, G6972650492, G7051064115
OpenAlex ID: W4412534827