title: Clustering of spatial gene expression patterns in the mouse brain and comparison with classical neuroanatomy.
abstract: Spatial gene expression profiles provide a novel means of exploring the structural organization of the brain. Computational analysis of these patterns is made possible by genome-scale mapping of the C57BL/6J mouse brain in the Allen Brain Atlas. Here we describe methodology used to explore the spatial structure of gene expression patterns across a set of 3041 genes chosen on the basis of consistency across experimental observations (N=2). The analysis was performed on smoothed, co-registered 3D expression volumes for each gene obtained by aggregating cellular resolution image data. Following dimensionality and noise reduction, voxels were clustered according to similarity of expression across the gene set. We illustrate the resulting parcellations of the mouse brain for different numbers of clusters (K) and quantitatively compare these parcellations with a classically-defined anatomical reference atlas at different levels of granularity, revealing a high degree of correspondence. These observations suggest that spatial localization of gene expression offers substantial promise in connecting knowledge at the molecular level with higher-level information about brain organization.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. jbohland@bu.edu
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bohland
authors.forename: Hemant
authors.initials: H
authors.lastname: Bokil
authors.forename: Sayan D
authors.initials: SD
authors.lastname: Pathak
authors.forename: Chang-Kyu
authors.initials: CK
authors.lastname: Lee
authors.forename: Lydia
authors.initials: L
authors.lastname: Ng
authors.forename: Christopher
authors.initials: C
authors.lastname: Lau
authors.forename: Chihchau
authors.initials: C
authors.lastname: Kuan
authors.forename: Michael
authors.initials: M
authors.lastname: Hawrylycz
authors.forename: Partha P
authors.initials: PP
authors.lastname: Mitra
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009445:Neuroanatomy / Q000379:methods; D012984:Software