Benchmarking macaque brain gene expression for horizontal and vertical translation
Andrea I. Luppi, Zhen-Qi Liu, Justine Y. Hansen, Rodrigo Cofré, Meiqi Niu, Elena Kuzmin, Seán Froudist‐Walsh, Nicola Palomero‐Gallagher, Bratislav Mišić
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.