Computational genetic neuroanatomy of the developing mouse brain: dimensionality reduction, visualization, and clustering

Shuiwang Ji

doi:10.1186/1471-2105-14-222

Abstract

BackgroundThe structured organization of cells in the brain plays a key role in its functional efficiency. This delicate organization is the consequence of unique molecular identity of each cell gradually established by precise spatiotemporal gene expression control during development. Currently, studies on the molecular-structural association are beginning to reveal how the spatiotemporal gene expression patterns are related to cellular differentiation and structural development.ResultsIn this article, we aim at a global, data-driven study of the relationship between gene expressions and neuroanatomy in the developing mouse brain. To enable visual explorations of the high-dimensional data, we map the in situ hybridization gene expression data to a two-dimensional space by preserving both the global and the local structures. Our results show that the developing brain anatomy is largely preserved in the reduced gene expression space. To provide a quantitative analysis, we cluster the reduced data into groups and measure the consistency with neuroanatomy at multiple levels. Our results show that the clusters in the low-dimensional space are more consistent with neuroanatomy than those in the original space.ConclusionsGene expression patterns and developing brain anatomy are closely related. Dimensionality reduction and visual exploration facilitate the study of this relationship.

Highlights

The structured organization of cells in the brain plays a key role in its functional efficiency
We study the relationship between brain anatomy and spatiotemporal gene expression patterns in the developing mouse brain
To study the developing mouse brain anatomy at multiple levels of granularity, we propagate the annotation of each voxel up to Level 5, Level 3, and Level 1, resulting in three annotated structures for each voxel that correspond to ancestor-child relations in the Reference Atlas ontology

Summary

Introduction

The structured organization of cells in the brain plays a key role in its functional efficiency This delicate organization is the consequence of unique molecular identity of each cell gradually established by precise spatiotemporal gene expression control during development. The delicate organization of brain into structures is the consequence of stringent spatiotemporal patterning controlled by the molecular signals during development. In this process, cells at different spatial locations read different morphogenetic positional signals produced by the graded distribution of signaling molecules. Studies on the molecularstructural associations are beginning to reveal how the spatiotemporal gene expression patterns are related to cellular differentiation and structural development [15,16,17,18]

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Results

Conclusion