Tera-MIND: Tera-scale mouse brain simulation via spatial mRNA-guided diffusion
Journal:
arXiv
Published Date:
Mar 3, 2025
Abstract
Holistic 3D modeling of molecularly defined brain structures is crucial for
understanding complex brain functions. Emerging tissue profiling technologies
enable the construction of a comprehensive atlas of the mammalian brain with
sub-cellular resolution and spatially resolved gene expression data. However,
such tera-scale volumetric datasets present significant computational
challenges in understanding complex brain functions within their native 3D
spatial context. Here, we propose the novel generative approach
$\textbf{Tera-MIND}$, which can simulate $\textbf{Tera}$-scale $\textbf{M}$ouse
bra$\textbf{IN}$s in 3D using a patch-based and boundary-aware
$\textbf{D}$iffusion model. Taking spatial transcriptomic data as the
conditional input, we generate virtual mouse brains with comprehensive cellular
morphological detail at teravoxel scale. Through the lens of 3D $gene$-$gene$
self-attention, we identify spatial molecular interactions for key
transcriptomic pathways in the murine brain, exemplified by glutamatergic and
dopaminergic neuronal systems. Importantly, these $in$-$silico$ biological
findings are consistent and reproducible across three tera-scale virtual mouse
brains. Therefore, Tera-MIND showcases a promising path toward efficient and
generative simulations of whole organ systems for biomedical research. Project
website: https://musikisomorphie.github.io/Tera-MIND.html
