WormGUIDES: an interactive single cell developmental atlas and tool for collaborative multidimensional data exploration

Abstract

BackgroundImaging and image analysis advances are yielding increasingly complete and complicated records of cellular events in tissues and whole embryos. The ability to follow hundreds to thousands of cells at the individual level demands a spatio-temporal data infrastructure: tools to assemble and collate knowledge about development spatially in a manner analogous to geographic information systems (GIS). Just as GIS indexes items or events based on their spatio-temporal or 4D location on the Earth these tools would organize knowledge based on location within the tissues or embryos. Developmental processes are highly context-specific, but the complexity of the 4D environment in which they unfold is a barrier to assembling an understanding of any particular process from diverse sources of information. In the same way that GIS aids the understanding and use of geo-located large data sets, software can, with a proper frame of reference, allow large biological data sets to be understood spatially. Intuitive tools are needed to navigate the spatial structure of complex tissue, collate large data sets and existing knowledge with this spatial structure and help users derive hypotheses about developmental mechanisms.ResultsToward this goal we have developed WormGUIDES, a mobile application that presents a 4D developmental atlas for Caenorhabditis elegans. The WormGUIDES mobile app enables users to navigate a 3D model depicting the nuclear positions of all cells in the developing embryo. The identity of each cell can be queried with a tap, and community databases searched for available information about that cell. Information about ancestry, fate and gene expression can be used to label cells and craft customized visualizations that highlight cells as potential players in an event of interest. Scenes are easily saved, shared and published to other WormGUIDES users. The mobile app is available for Android and iOS platforms.ConclusionWormGUIDES provides an important tool for examining developmental processes and developing mechanistic hypotheses about their control. Critically, it provides the typical end user with an intuitive interface for developing and sharing custom visualizations of developmental processes. Equally important, because users can select cells based on their position and search for information about them, the app also serves as a spatially organized index into the large body of knowledge available to the C. elegans community online. Moreover, the app can be used to create and publish the result of exploration: interactive content that brings other researchers and students directly to the spatio-temporal point of insight. Ultimately the app will incorporate a detailed time lapse record of cell shape, beginning with neurons. This will add the key ability to navigate and understand the developmental events that result in the coordinated and precise emergence of anatomy, particularly the wiring of the nervous system.

Visualizing Calcium Flux in Freely Moving Nematode Embryos

“…Detailed behavioral characterization of the embryo in the post-twitching regime will help focus future calcium imaging experiments to periods when neural circuits are wiring up and coming online. We anticipate that functional data will add a valuable layer of information to cross reference with the rich anatomical and gene expression datasets already available in C. elegans (46). …”

Coordinated morphogenesis of neurons and glia

“…This allows acquisition of clear images through the complete volume of the embryo despite embryonic twitching movements. In addition to these advances in image acquisition, novel post-processing techniques have made it feasible to track single cell movements within the moving embryo[49,50]. Armed with these advances, efforts are now underway to generate large-scale atlases of all cellular positions throughout embryogenesis[49].…”

“…In addition to these advances in image acquisition, novel post-processing techniques have made it feasible to track single cell movements within the moving embryo[49,50]. Armed with these advances, efforts are now underway to generate large-scale atlases of all cellular positions throughout embryogenesis[49]. In conjunction with recent advances in EM of defined embryonic stages[51], these techniques will facilitate additional studies of neuron-glia contact formation by revealing how neurons and glia move relative to one another in the developing embryo.…”

The need to connect: on the cell biology of synapses, behaviors, and networks in science

“…We established collaborations to develop and use new instrumentation and approaches for better visualization of the events leading to correct synaptogenesis (Rankin et al. , 2011; Wu et al , 2011, 2013a, b; Kumar et al , 2014; Christensen et al , 2015; Santella et al , 2015). We also collaborate to visualize neuronal activity and thermotactic behavior in C. elegans (Ha et al , 2010; Luo et al , 2014a, b).…”