Abstract
Finding links between genes and structural connectivity is of the utmost importance for unravelling the underlying mechanism of the brain connectome. In this study we identify links between the gene expression and the axonal projection density in the mouse brain, by applying a modified version of the Linked ICA method to volumetric data from the Allen Institute for Brain Science for identifying independent sources of information that link both modalities at the voxel level. We performed separate analyses on sets of projections from the visual cortex, the caudoputamen and the midbrain reticular nucleus, and we determined those brain areas, injections and genes that were most involved in independent components that link both gene expression and projection density data, while we validated their biological context through enrichment analysis. We identified representative and literature-validated cortico-midbrain and cortico-striatal projections, whose gene subsets were enriched with annotations for neuronal and synaptic function and related developmental and metabolic processes. The results were highly reproducible when including all available projections, as well as consistent with factorisations obtained using the Dictionary Learning and Sparse Coding technique. Hence, Linked ICA yielded reproducible independent components that were preserved under increasing data variance. Taken together, we have developed and validated a novel paradigm for linking gene expression and structural projection patterns in the mouse mesoconnectome, which can power future studies aiming to relate genes to brain function.
Highlights
Bridging the gap between genes and brain structural connectivity is of the utmost importance to make further progress in neuroscience
In this study we simultaneously identify links between the gene expression and the axonal projection density in the mouse brain, using volumetric data from the Allen Institute for Brain Science and applying a modified version of the Linked ICA method (Groves et al 2011) to identify independent sources of information that link both modalities at the voxel level
The aim of this study is the identification of links between volumetric gene expression and axonal projection density data, that were made publicly available by the Allen Institute (Lein et al 2007; Oh et al 2014)
Summary
Bridging the gap between genes and brain structural connectivity is of the utmost importance to make further progress in neuroscience. The new studies centered around investigating associations between the spatial organization of gene expression and properties related to brain structure or function (Lein et al 2007; Hawrylycz et al 2009; Keil et al 2018). In tandem with this new era of spatial transcriptomics, Roy et al and Zhu et al investigated its proteomic counterpart. They found postsynaptic protein profiles of excitatory synapses to be markers of synaptic diversity patterns across brain regions that account for different brain networks (Roy et al 2018; Zhu et al 2018)
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