title: Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.
abstract: Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Shen-Ju
authors.initials: SJ
authors.lastname: Chou
authors.affiliation: Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Chindi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Nardnisa
authors.initials: N
authors.lastname: Sintupisut
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Niou
authors.affiliation: Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Chih-Hsu
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Ker-Chau
authors.initials: KC
authors.lastname: Li
authors.affiliation: Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Yeang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D060850:LIM-Homeodomain Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000172:deficiency; D059467:Transcriptome
chemical_list: D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors