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Benchmarking macaque brain gene expression for horizontal and vertical translation.

Andrea I Luppi1,2,3, Zhen-Qi Liu1, Justine Y Hansen1

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Macaque gene expression partially mirrors protein patterns and human gene expression, with better alignment in specific cortical layers and unimodal regions. This highlights macaque transcriptomics

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Area of Science:

  • Neuroscience
  • Genomics
  • Comparative Biology

Background:

  • The macaque is a key model organism for studying brain function.
  • Translational neuroscience relies on macaque gene expression accurately reflecting protein levels and human gene patterns.

Purpose of the Study:

  • To systematically evaluate the accuracy of macaque cortical gene expression as a proxy for protein levels and human gene expression.
  • To assess the translational potential of macaque transcriptomics for neuroscience research.

Main Methods:

  • Benchmarking regional macaque cortical gene expression against macaque protein receptor density, microstructure, and human cortical gene expression.
  • Analyzing gene expression patterns in both cortex-wide and layer-specific contexts.
  • Comparing interspecies gene expression correspondence between unimodal and transmodal cortical areas.

Main Results:

  • Moderate overall correlation found between macaque gene expression and protein density, significantly improving with layer-specific analysis.
  • Approximately 50% of investigated genes showed significant cross-species (macaque-human) correlation in cortical expression.
  • Gene expression correspondence between species was stronger in unimodal cortex than in transmodal cortex.

Conclusions:

  • Macaque cortical gene expression shows moderate but imperfect correspondence with protein levels and human orthologs.
  • Layer-specific analysis enhances the predictive power of macaque gene expression for protein levels.
  • The findings underscore both the utility and limitations of macaque transcriptomics for translational research across species and within the macaque itself.