title: Visualizing the spatial gene expression organization in the brain through non-linear similarity embeddings.
abstract: The Allen Brain Atlases enable the study of spatially resolved, genome-wide gene expression patterns across the mammalian brain. Several explorative studies have applied linear dimensionality reduction methods such as Principal Component Analysis (PCA) and classical Multi-Dimensional Scaling (cMDS) to gain insight into the spatial organization of these expression patterns. In this paper, we describe a non-linear embedding technique called Barnes-Hut Stochastic Neighbor Embedding (BH-SNE) that emphasizes the local similarity structure of high-dimensional data points. By applying BH-SNE to the gene expression data from the Allen Brain Atlases, we demonstrate the consistency of the 2D, non-linear embedding of the sagittal and coronal mouse brain atlases, and across 6 human brains. In addition, we quantitatively show that BH-SNE maps are superior in their separation of neuroanatomical regions in comparison to PCA and cMDS. Finally, we assess the effect of higher-order principal components on the global structure of the BH-SNE similarity maps. Based on our observations, we conclude that BH-SNE maps with or without prior dimensionality reduction (based on PCA) provide comprehensive and intuitive insights in both the local and global spatial transcriptome structure of the human and mouse Allen Brain Atlases.
authors.affiliation: Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mahfouz
authors.affiliation: Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: van de Giessen
authors.affiliation: Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
authors.forename: Laurens
authors.initials: L
authors.lastname: van der Maaten
authors.affiliation: Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Huisman
authors.affiliation: Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Reinders
authors.affiliation: Allen Institute for Brain Science, Seattle, WA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawrylycz
authors.affiliation: Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands. Electronic address: b.p.f.lelieveldt@lumc.nl.
authors.forename: Boudewijn P F
authors.initials: BP
authors.lastname: Lelieveldt
mesh_terms: D000328:Adult; D000818:Animals; D001271:Atlases as Topic; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D017711:Nonlinear Dynamics; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
keywords: Allen Brain Atlas; Brain transcriptome structure; Dimensionality reduction; Spatial-mapped gene expression; Stochastic Neighbor Embedding