title: A digital framework to build, visualize and analyze a gene expression atlas with cellular resolution in zebrafish early embryogenesis.
abstract: A gene expression atlas is an essential resource to quantify and understand the multiscale processes of embryogenesis in time and space. The automated reconstruction of a prototypic 4D atlas for vertebrate early embryos, using multicolor fluorescence in situ hybridization with nuclear counterstain, requires dedicated computational strategies. To this goal, we designed an original methodological framework implemented in a software tool called Match-IT. With only minimal human supervision, our system is able to gather gene expression patterns observed in different analyzed embryos with phenotypic variability and map them onto a series of common 3D templates over time, creating a 4D atlas. This framework was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf (hours post fertilization). They included 53 specimens, 181,415 detected cell nuclei and the segmentation of 98 gene expression patterns observed in 3D for 9 different genes. In addition, an interactive visualization software, Atlas-IT, was developed to inspect, supervise and analyze the atlas. Match-IT and Atlas-IT, including user manuals, representative datasets and video tutorials, are publicly and freely available online. We also propose computational methods and tools for the quantitative assessment of the gene expression templates at the cellular scale, with the identification, visualization and analysis of coexpression patterns, synexpression groups and their dynamics through developmental stages.
authors.affiliation: Biomedical Image Technologies, ETSIT, Universidad Politécnica de Madrid, CEIMoncloa, Madrid, Spain; Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Madrid-MIT M+Visión Consortium, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Carlos
authors.initials: C
authors.lastname: Castro-González
authors.affiliation: Biomedical Image Technologies, ETSIT, Universidad Politécnica de Madrid, CEIMoncloa, Madrid, Spain; Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Luengo-Oroz
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Duloquin
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Savy
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rizzi
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Desnoulez
authors.affiliation: Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; School of Biomedical Engineering, Drexel University, Philadelphia, Pennsylvania, United States of America.
authors.forename: René
authors.initials: R
authors.lastname: Doursat
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; LIMICS-INSERM UMR 1142, UFR SMBH, Université Paris 13, Bobigny, France.
authors.forename: Yannick L
authors.initials: YL
authors.lastname: Kergosien
authors.affiliation: Biomedical Image Technologies, ETSIT, Universidad Politécnica de Madrid, CEIMoncloa, Madrid, Spain; Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Ledesma-Carbayo
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Bourgine
authors.affiliation: MDAM UPR3294, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France; Institut des Systèmes Complexes, Paris, France; BioEmergences-IBiSA, Institut de Neurobiologie Alfred Fessard, CNRS, Gif-sur-Yvette, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Peyriéras
authors.affiliation: Biomedical Image Technologies, ETSIT, Universidad Politécnica de Madrid, CEIMoncloa, Madrid, Spain; Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Santos
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D059467:Transcriptome / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism*