MOTIVATION: A comprehensive gene expression database is essential for computer modeling and simulation of biological phenomena, including development. Development is a four-dimensional (4D; 3D structure and time course) phenomenon. We are constructing a 4D database of gene expression for the early embryogenesis of the nematode Caenorhabditis elegans. As a framework of the 4D database, we have constructed computer graphics (CG), into which we will incorporate the expression data of a number of genes at the subcellular level. However, the assignment of 3D distribution of gene products (protein, mRNA), of embryos at various developmental stages, is both difficult and tedious. We need to automate this process. For this purpose, we developed a new system, named SPI after superimposing fluorescent confocal microscopic data onto a CG framework. RESULTS: The scheme of this system comprises the following: (1) acquirement of serial sections (40 slices) of fluorescent confocal images of three colors (4',6'-diamino-2-phenylindole (DAPI) for nuclei, indodicarbocyanine (Cy-3) for the internal marker, which is a germline-specific protein POS-1 and indocarbocyanine (Cy-5) for the gene product to be examined); (2) identification of several features of the stained embryos, such as contour, developmental stage and position of the internal marker; (3) selection of CG images of the corresponding stage for template matching; (4) superimposition of serial sections onto the CG; (5) assignment of the position of superimposed gene products. The Snakes algorithm identified the embryo contour. The detection accuracy of embryo contours was 92.1% when applied to 2- to 28-cell-stage embryos. The accuracy of the developmental stage prediction method was 81.2% for 2- to 8-cell-stage embryos. We manually judged only the later stage embryos because the accuracy for embryos at the later stages was unsatisfactory due to experimental noise effects. Finally, our system chose the optimal CG and performed the superposition and assignment of gene product distribution. We established an initial 4D gene expression database with 56 maternal gene products. AVAILABILITY: This system is available at http://anti.lab.nig.ac.jp/spi/ and http://anti.lab.nig.ac.jp/4ddb/

MOTIVATION: The ultimate goal of bioinformatics is to reconstruct biological systems in the computer. Since biological systems have many levels, it is important to focus on an appropriate level. In our first application of computer modeling to the early development of the nematode Caenorhabditis elegans, we focus on the cellular arrangement in early embryos. This plays a very important role in cell fate determination by cell-cell interaction, and is regarded as a system, one level higher than the system of gene regulation within cells. It is largely restricted by physical conditions that seemed feasible to model by computer. RESULTS: We constructed a computer model of the C.elegans embryo, currently up to the 4-cell stage, using a deformable and dividable triangulated network. The model is based solely on cellular-level dynamics. We found that the optimal ranges of three parameters that affect the elongation of dividing cells led, in computer simulations, to almost the same cellular arrangements as in real embryos. The nature of the model and the relationship with real embryos are discussed.