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

Ji S - BMC Bioinformatics (2013)

Bottom Line: 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.Dimensionality reduction and visual exploration facilitate the study of this relationship.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, Old Dominion University, 4700 Elkhorn Avenue, Suite 3300, Norfolk, VA 23529-0162, USA. sji@cs.odu.edu

ABSTRACT

Background: 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. 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.

Results: In 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.

Conclusions: Gene expression patterns and developing brain anatomy are closely related. Dimensionality reduction and visual exploration facilitate the study of this relationship.

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Related in: MedlinePlus

The Allen Developing Mouse Brain Reference Atlas ontology hierarchy through level 5. Each ontological term corresponds to a node in the hierarchy, labeled by the abbreviation followed by the level number inside a parenthesis. The nodes are color-coded as in the original atlas in Figure 1. The transverse segments lie at level 3, and they are combined with the longitudinal zones at level 5 to generate the grid-like pattern. We up-propagate the voxel annotations to levels 1, 3, and 5, respectively, in our experiments in order to study the gene expressions in the grid-like longitudinal and transversal domains.
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Figure 2: The Allen Developing Mouse Brain Reference Atlas ontology hierarchy through level 5. Each ontological term corresponds to a node in the hierarchy, labeled by the abbreviation followed by the level number inside a parenthesis. The nodes are color-coded as in the original atlas in Figure 1. The transverse segments lie at level 3, and they are combined with the longitudinal zones at level 5 to generate the grid-like pattern. We up-propagate the voxel annotations to levels 1, 3, and 5, respectively, in our experiments in order to study the gene expressions in the grid-like longitudinal and transversal domains.

Mentions: The Reference Atlas ontology was created based on the prosomeric model, which proposes that the developing brain is divided along the transversal and longitudinal boundaries, giving rise to a grid-like pattern (Figure 1). The ontology was designed to capture the progressive development and regionalization of the nervous system. An ontological term at each level has multiple child terms at the next level, reflecting the subdivision of the corresponding structure into multiple substructures. By this construction, the Reference Atlas ontology forms a 13-level hierarchy in which the root corresponds to the undivided neural plate. The ontology was colorized so that anatomically and developmentally related structures are coded with similar colors. The ontology from Level 0 to Level 5 is shown in Figures 2 and 3.


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

Ji S - BMC Bioinformatics (2013)

The Allen Developing Mouse Brain Reference Atlas ontology hierarchy through level 5. Each ontological term corresponds to a node in the hierarchy, labeled by the abbreviation followed by the level number inside a parenthesis. The nodes are color-coded as in the original atlas in Figure 1. The transverse segments lie at level 3, and they are combined with the longitudinal zones at level 5 to generate the grid-like pattern. We up-propagate the voxel annotations to levels 1, 3, and 5, respectively, in our experiments in order to study the gene expressions in the grid-like longitudinal and transversal domains.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750329&req=5

Figure 2: The Allen Developing Mouse Brain Reference Atlas ontology hierarchy through level 5. Each ontological term corresponds to a node in the hierarchy, labeled by the abbreviation followed by the level number inside a parenthesis. The nodes are color-coded as in the original atlas in Figure 1. The transverse segments lie at level 3, and they are combined with the longitudinal zones at level 5 to generate the grid-like pattern. We up-propagate the voxel annotations to levels 1, 3, and 5, respectively, in our experiments in order to study the gene expressions in the grid-like longitudinal and transversal domains.
Mentions: The Reference Atlas ontology was created based on the prosomeric model, which proposes that the developing brain is divided along the transversal and longitudinal boundaries, giving rise to a grid-like pattern (Figure 1). The ontology was designed to capture the progressive development and regionalization of the nervous system. An ontological term at each level has multiple child terms at the next level, reflecting the subdivision of the corresponding structure into multiple substructures. By this construction, the Reference Atlas ontology forms a 13-level hierarchy in which the root corresponds to the undivided neural plate. The ontology was colorized so that anatomically and developmentally related structures are coded with similar colors. The ontology from Level 0 to Level 5 is shown in Figures 2 and 3.

Bottom Line: 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.Dimensionality reduction and visual exploration facilitate the study of this relationship.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, Old Dominion University, 4700 Elkhorn Avenue, Suite 3300, Norfolk, VA 23529-0162, USA. sji@cs.odu.edu

ABSTRACT

Background: 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. 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.

Results: In 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.

Conclusions: Gene expression patterns and developing brain anatomy are closely related. Dimensionality reduction and visual exploration facilitate the study of this relationship.

Show MeSH
Related in: MedlinePlus