title: A computational approach towards a gene regulatory network for the developing Nematostella vectensis gut.
abstract: BACKGROUND
  The starlet sea anemone Nematostella vectensis is a diploblastic cnidarian that expresses a set of conserved genes for gut formation during its early development. During the last decade, the spatial distribution of many of these genes has been visualized with RNA hybridization or protein immunolocalization techniques. However, due to N. vectensis' curved and changing morphology, quantification of these spatial data is problematic. A method is developed for two-dimensional gene expression quantification, which enables a numerical analysis and dynamic modeling of these spatial patterns.
  
  
  RESULTS
  In this work, first standardized gene expression profiles are generated from publicly available N. vectensis embryo images that display mRNA and/or protein distributions. Then, genes expressed during gut formation are clustered based on their expression profiles, and further grouped based on temporal appearance of their gene products in embryonic development. Representative expression profiles are manually selected from these clusters, and used as input for a simulation-based optimization scheme. This scheme iteratively fits simulated profiles to the selected profiles, leading to an optimized estimation of the model parameters. Finally, a preliminary gene regulatory network is derived from the optimized model parameters.
  
  
  CONCLUSIONS
  While the focus of this study is N. vectensis, the approach outlined here is suitable for inferring gene regulatory networks in the embryonic development of any animal, thus allowing to comparatively study gene regulation of gut formation in silico across various species.
authors: Computational Science, University of Amsterdam, Amsterdam, The Netherlands.
authors: Daniel
authors: D
authors: Botman
authors: Université Nice Sophia Antipolis, Institute for Research on Cancer and Aging, Nice (IRCAN), UMR 7284, Nice, France; Centre National de la Recherche Scientifique (CNRS), Institute for Research on Cancer and Aging, Nice (IRCAN), UMR 7284, Nice, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research on Cancer and Aging, Nice (IRCAN), U1081, Nice, France.
authors: Eric
authors: E
authors: Röttinger
authors: Whitney Lab for Marine Bioscience, University of Florida, St. Augustine, Florida, United States of America.
authors: Mark Q
authors: MQ
authors: Martindale
authors: Computational Cancer Biology Group, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors: Johann
authors: J
authors: de Jong
authors: Computational Science, University of Amsterdam, Amsterdam, The Netherlands.
authors: Jaap A
authors: JA
authors: Kaandorp
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D047108:Embryonic Development / Q000235:genetics; D041981:Gastrointestinal Tract / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D038081:Organogenesis / Q000235:genetics; D012615:Sea Anemones / Q000196:embryology* / Q000235:genetics*