title: Transcriptome tomography for brain analysis in the web-accessible anatomical space.
abstract: Increased information on the encoded mammalian genome is expected to facilitate an integrated understanding of complex anatomical structure and function based on the knowledge of gene products. Determination of gene expression-anatomy associations is crucial for this understanding. To elicit the association in the three-dimensional (3D) space, we introduce a novel technique for comprehensive mapping of endogenous gene expression into a web-accessible standard space: Transcriptome Tomography. The technique is based on conjugation of sequential tissue-block sectioning, all fractions of which are used for molecular measurements of gene expression densities, and the block- face imaging, which are used for 3D reconstruction of the fractions. To generate a 3D map, tissues are serially sectioned in each of three orthogonal planes and the expression density data are mapped using a tomographic technique. This rapid and unbiased mapping technique using a relatively small number of original data points allows researchers to create their own expression maps in the broad anatomical context of the space. In the first instance we generated a dataset of 36,000 maps, reconstructed from data of 61 fractions measured with microarray, covering the whole mouse brain (ViBrism: http://vibrism.riken.jp/3dviewer/ex/index.html) in one month. After computational estimation of the mapping accuracy we validated the dataset against existing data with respect to the expression location and density. To demonstrate the relevance of the framework, we showed disease related expression of Huntington's disease gene and Bdnf. Our tomographic approach is applicable to analysis of any biological molecules derived from frozen tissues, organs and whole embryos, and the maps are spatially isotropic and well suited to the analysis in the standard space (e.g. Waxholm Space for brain-atlas databases). This will facilitate research creating and using open-standards for a molecular-based understanding of complex structures; and will contribute to new insights into a broad range of biological and medical questions.
authors.affiliation: Advanced Computational Sciences Department, Advanced Science Institute (ASI), RIKEN, Saitama, Japan. yoho@brent-research.org
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamura-Oho
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shimokawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Takemoto
authors.forename: Asami
authors.initials: A
authors.lastname: Hirakiyama
authors.forename: Sakiko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tsujimura
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Takeya
authors.initials: T
authors.lastname: Kasukawa
authors.forename: Koh-hei
authors.initials: KH
authors.lastname: Masumoto
authors.forename: Itoshi
authors.initials: I
authors.lastname: Nikaido
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shigeyoshi
authors.forename: Hiroki R
authors.initials: HR
authors.lastname: Ueda
authors.forename: Gang
authors.initials: G
authors.lastname: Song
authors.forename: James
authors.initials: J
authors.lastname: Gee
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Himeno
authors.forename: Hideo
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D006816:Huntington Disease; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059467:Transcriptome / Q000235:genetics*