A 3D digital atlas of C. elegans and its application to single-cell analyses

Abstract

We have built a digital nuclear atlas of the newly hatched, first larval stage (L1) of the wild type hermaphrodite of C. elegans at single cell resolution from confocal image stacks of 15 individuals. The atlas quantifies the stereotypy of the locations and provides for other statistics on the spatial patterns of the 357 nuclei that could be faithfully segmented and annotated of the 558 present at this developmental stage. Given this atlas we then developed an automated approach to assign cell names to each nucleus in a 3D image of an L1 worm. We achieve 86% accuracy in identifying the 357 nuclei automatically. This computational method is essential for high-throughput single cell analyses of the worm at post-embryonic stages, such as determining the expression of every gene in every cell during development from the L1 onward, or ablating or stimulating cells under computer control in a high-throughput functional screen.

Active Graph Matching for Automatic Joint Segmentation and Annotation of C. elegans

“…Since C. elegans is highly stereotypical it is well suited for comparative developmental studies. A common and time consuming problem in such studies is the segmentation and annotation of cell nuclei with their unique biological names in 3D microscopic images [1,2,3,4]. This work presents a fully automated joint segmentation and annotation method for this task.…”

“…Previous approaches for automatic annotation of nuclei in C. elegans [2,3,4] build an average atlas of nuclei locations, and annotate new target worms by mapping the atlas to them. One approach finds a globally optimal one-to-one mapping but is agnostic to covariances between nucleus positions [2,3].…”

“…One approach finds a globally optimal one-to-one mapping but is agnostic to covariances between nucleus positions [2,3]. Another approach incorporates heuristic prior knowledge on relative positions of nuclei in the form of a local deformation model, but does not tackle local deformation and mapping of nuclei jointly in a globally optimal way [4].…”

Assembling models of embryo development: Image analysis and the construction of digital atlases

“…The nematode Coenorhabditis elegans, having the most ancient evolutionary emergence among the considered animal models, has a largely invariant cell lineage and stereotyped development which greatly facilitates comparisons between different individuals (Murray et al, 2008;Liu et al, 2009;Long et al, 2009).…”

Towards a digital model of zebrafish embryogenesis. Integration of cell tracking and gene expression quantification

“…Capturing quantitative data of gene expression in time and space at the single cell resolution becomes then a crucial step to fulfill this goal. This topic has been approached by a few big projects [7] [3] [6] concerning different animal models: the C. elegans, the Drosophila and the mouse brain. Our focus is on the zebrafish (Danio rerio) embryo which, due to its embryonic optical transparency, quick growth and similarities to human differentiated cell types, provides an interesting system to study vertébrate development.…”