Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse

PLoS One. 2015 Feb 23;10(2):e0118024. doi: 10.1371/journal.pone.0118024. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choroid Plexus / embryology
  • Choroid Plexus / metabolism
  • Computational Biology / methods*
  • Databases, Genetic
  • Ear, Inner / embryology
  • Ear, Inner / metabolism
  • Fetal Development / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Gene Regulatory Networks
  • Genomics / methods
  • Humans
  • In Situ Hybridization / methods*
  • Information Storage and Retrieval / methods
  • Mice
  • Olfactory Mucosa / embryology
  • Olfactory Mucosa / metabolism
  • Retina / embryology
  • Retina / metabolism
  • Sensory Receptor Cells / metabolism
  • Vibrissae / embryology
  • Vibrissae / metabolism

Grants and funding

The present work was funded by the grants from the European Union (6th Framework Program, EURExpress integrated project, LSHG-CT-2004-512003), the Agence Nationale de la Recherche (ANR Neurosciences 2007 and Programme blanc 2011), Fondation pour la Recherche Médicale (Equipe FRM 2007) (to P.D.); ANR BIPBIP: ANR-10-BINF-03-05 (to O.P.) and the CNRS, INSERM, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Région Alsace. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.