Benchmarking macaque brain gene expression for horizontal and vertical translation
Open accessPublished version of a preprint
Abstract
The spatial patterning of gene expression shapes cortical organization and function. The macaque is a fundamental model organism in neuroscience, but the translational potential of macaque gene expression rests on the assumption that it is a good proxy for patterns of corresponding proteins (vertical translation) and for patterns of orthologous human genes (horizontal translation). Here, we systematically benchmark regional gene expression in macaque cortex against (i) macaque cortical receptor density and in vivo and ex vivo microstructure and (ii) human cortical gene expression. We find moderate cortex-wide correspondence between macaque gene expression and protein density, which improves by considering layer-specific gene expression. Half of the examined genes exhibit significant correlation between macaque and human across the cortex. Interspecies correspondence of gene expression is greater in unimodal than in transmodal cortex, recapitulating evolutionary cortical expansion and gene-protein correspondence in the macaque. These results showcase the potential and limitations of macaque cortical transcriptomics for translational discovery within and across species.
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- Authors
- Luppi, A. I., Liu, Z.-Q., Hansen, J. Y., Cofre, R., Niu, M., Kuzmin, E., Froudist-Walsh, S., Palomero-Gallagher, N., & Misic, B.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Paris-Saclay University, CNRS, Paris-Saclay Institute for Neuroscience (NeuroPSI), Saclay, France.
- Forschungszentrum Jülich (DE)
- Institut du cancer Rosalind & Morris Goodman (CA)
- Bristol Computational Neuroscience Unit, Bristol University, Bristol, UK.
- Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
- Montréal Neurological Institute, McGill University, Montréal, QC, Canada.
- Corresponding author
- Luppi, Andrea I.
- ORCID
- Venue
- Science Advances
- Published
- 2025-02-28
- Volume
- 11
- Issue
- 9
- Pages
- eads6967-eads6967
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC11870082
- OpenAlex
- W4408030000
- Cited by
- 14
- References
- 11
- Citations by year
- 2026: 10 · 2025: 4
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Science Advances (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust (226924)
- Biotechnology and Biological Sciences Research Council (BB/X013243/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- macaque cortex, gene expression, vertical translation, horizontal translation, cortical microstructure, cortical layers, cortical evolution, translational validity
- MeSH terms
- Animals, Brain, Cerebral Cortex, Gene Expression Regulation, Humans, Macaca, Protein Biosynthesis, Gene Expression, Benchmarking, Gene Expression Profiling, Transcriptome
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