title: Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse.
abstract: An in situ hybridization (ISH) study was performed on 2000 murine genes representing around 10% of the protein-coding genes present in the mouse genome using data generated by the EURExpress consortium. This study was carried out in 25 tissues of late gestation embryos (E14.5), with a special emphasis on the developing ear and on five distinct developing sensory organs, including the cochlea, the vestibular receptors, the sensory retina, the olfactory organ, and the vibrissae follicles. The results obtained from an analysis of more than 11,000 micrographs have been integrated in a newly developed knowledgebase, called ImAnno. In addition to managing the multilevel micrograph annotations performed by human experts, ImAnno provides public access to various integrated databases and tools. Thus, it facilitates the analysis of complex ISH gene expression patterns, as well as functional annotation and interaction of gene sets. It also provides direct links to human pathways and diseases. Hierarchical clustering of expression patterns in the 25 tissues revealed three main branches corresponding to tissues with common functions and/or embryonic origins. To illustrate the integrative power of ImAnno, we explored the expression, function and disease traits of the sensory epithelia of the five presumptive sensory organs. The study identified 623 genes (out of 2000) concomitantly expressed in the five embryonic epithelia, among which many (∼12%) were involved in human disorders. Finally, various multilevel interaction networks were characterized, highlighting differential functional enrichments of directly or indirectly interacting genes. These analyses exemplify an under-represention of "sensory" functions in the sensory gene set suggests that E14.5 is a pivotal stage between the developmental stage and the functional phase that will be fully reached only after birth.
authors.affiliation: Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, Université de Strasbourg), BP163, 67404 Illkirch Cedex, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Romand
authors.affiliation: Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, Université de Strasbourg), BP163, 67404 Illkirch Cedex, France; LBGI Bioinformatique et Génomique Intégratives, ICube Laboratory and Strasbourg Federation of Translational Medecine (FMTS), University of Strasbourg and CNRS, Strasbourg, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Ripp
authors.affiliation: LBGI Bioinformatique et Génomique Intégratives, ICube Laboratory and Strasbourg Federation of Translational Medecine (FMTS), University of Strasbourg and CNRS, Strasbourg, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Poidevin
authors.affiliation: Imaging & Microscopy Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, Université de Strasbourg), BP163, 67404 Illkirch Cedex, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Boeglin
authors.affiliation: Department of Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Geffers
authors.affiliation: Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, Université de Strasbourg), BP163, 67404 Illkirch Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.affiliation: LBGI Bioinformatique et Génomique Intégratives, ICube Laboratory and Strasbourg Federation of Translational Medecine (FMTS), University of Strasbourg and CNRS, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
mesh_terms: D000818:Animals; D002831:Choroid Plexus / Q000196:embryology / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D007758:Ear, Inner / Q000196:embryology / Q000378:metabolism; D047109:Fetal Development / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D016247:Information Storage and Retrieval / Q000379:methods; D051379:Mice; D009831:Olfactory Mucosa / Q000196:embryology / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D014738:Vibrissae / Q000196:embryology / Q000378:metabolism