1. Timothy Durham [email protected]
2. Andrew Hill [email protected]
3. Melissa Chiasson [email protected]

Caenorhabditis elegans (C. elegans) is small roundworm used widely as a model organism in genetics and genomics. Its development has been well studied; each worm takes around 14 hours to grow from a single fertilized cell to a hatched larvae with 558 cells. This process of embryonic development progresses in a stereotyped pattern that follows an invariant cell lineage; the same branches in this tree always produce the same tissues in the hatched worm. We have a dataset that describes the spatial orientation of every cell throughout C. elegans embryo development time points, along with their lineages (which cell derives from which) and cell type. Despite intense study of C. elegans, currently there does not exist a resource where one can interactively visualize C. elegans embryo development through time and interrogate what cells are located where, which lineages they are in, and what cell type they are.

Access our visualization at http://cse512-15s.github.io/a3-tdurham-ajh24-chiasson/ or download this repository and run python -m SimpleHTTPServer 2255 and access this from http://localhost:2255/.

We recommend using either Chrome or Opera for ideal viewing.

We wanted to address this lack of resource, since it would be a great tool for the C. elegans community. In initial discussions, we decided we wanted to show both a 3D representation of the worm embryo throughout development and the classic C. elegans cell lineage tree.

Most of our understandings of cell-cell connections and spatial relationships in development comes from two-dimensional representations, either views through a microscope or in other representations like the lineage tree. While these representations can be very effective, we sought to address two important limitations with our 3D approach. First, embryogenesis is a biological process takes place in three dimensions, and the orientations and connections among cells play an essential role in this process. Being able to identify cells and to watch them undergo divisions and migrations in three dimensions, from any orientation, can greatly facilitate our understanding of which lineages are close together and which cell-cell connections might be important in forming different tissues. For example, at the gastrulation stage of development the cells that go on to form the intestine migrate dorsally from ventral locations on the outside of the embryo to locations inside the embryo, with other cells migrating ventrally to fill in the space left by their migration. When the intestinal cell type is highlighted in our 3D plot, this migration can be observed clearly from any orientation, and other interacting lineages and cell types can be identified by using the multiple lineage highlighting feature.

Another interesting lineage is the C lineage. By the end of our time series, cells from the C lineage migrate to the posterior-dorsal edge of the embryo, forming a complex curvature around the back of the embryo from left to right. Patterns like this are much harder to understand in two-dimensions, and our 3D plot provides a more natural way to gain this insight. Despite the advantages of the ability to view the developing embryo in three dimensions, we wanted a more familiar plot to help ground this visualization in a visual language that is more familiar to the C. elegans community. To this end, we decided that we should show the lineage tree to help facilitate the identification of specific cells and lineages and to provide this familiar context.

We thought it would be ideal if you could highlight specific cells and their lineages or cell types with color and get their locations on the lineage tree. We also wanted to add a slider that you could use to navigate back and forth through developmental time.

Since we were all unfamiliar with D3, we figured our first goal would be to get the 3D embryo visualization working with a lineage map displayed next to it, with the aim that if we got this to work and still had more time, we could implement additional features.

Our final design exceeded our initial goals. We have a slider that one can use to navigate the 3D embryo animation visualization in time, plus a dropdown menu to control the speed at which this animation plays. In synchrony with the 3D visualization, the lineage tree colors in nodes of cells as they appear. We also have a dropdown menu with a quick search function to highlight specific cell lineages or cell types within the animation and within the lineage tree (this can also be hidden with a collapse button). Cells are highlighted throughout the animation, and cells that aren’t of interest can be hidden by clicking “Hide non-highlighted.” Highlight color can be changed using a color menu. Multiple highlights can be applied by pressing the “+” below the menu bar. One challenge we faced with the lineage tree is that it is extremely wide and information-rich. In order to display both the broader tree context and information about specific nodes and branches, we implemented a Cartesian distortion that expands the tree like an accordion along the x-axis, zooming in to show details. The user can the distortion back and forth along the breadth of the tree using a slider bar.

For the development process, we discussed the initial data set and storyboard idea together, then reconvened later to discuss the next set of goals once we had the basics of the original storyboard programmed. In all, we spent approximately 125 hours putting this visualization together. For all three members, a significant portion of time was spent getting familiar with javascript and D3. The elements of this project that took the most time were data loading (both the cell coordinates and cell type to cell name mappings), the cell and cell type highlighting, synchronization of the animation with the lineage tree, applying distortion to the tree, and general styling of the graphics. All members collaborated on designing the visualization and addressing features of interest. Tim worked on data loading, synchronization of the 3D animation and tree, and cell highlighting features. Andrew worked on making the lineage tree, finding the best representation of it, and then implementing distortion to further improve tree presentation. Melissa worked on the animation playback feature and prepared the final write-up.