Deep learning-based enhancement of fluorescence labeling for accurate cell lineage tracing during embryogenesis

Automated cell lineage tracing throughout embryogenesis plays a key role in the study of regulatory control of cell fate differentiation, morphogenesis and organogenesis in the development of animals, including nematode Caenorhabditis elegans. However, automated cell lineage tracing suffers from an exponential increase in errors at late embryo because of the dense distribution of cells, relatively low signal-to-noise ratio (SNR) and imbalanced intensity profiles of fluorescence images, which demands a huge amount of human effort to manually correct the errors. The existing image enhancement methods are not sensitive enough to deal with the challenges posed by the crowdedness and low signal-to-noise ratio. An alternative method is urgently needed to assist the existing detection methods in improving their detection and tracing accuracy, thereby reducing the huge burden for manual curation.

We developed a new method, termed as DELICATE, that dramatically improves the accuracy of automated cell lineage tracing especially during the stage post 350 cells of C. elegans embryo. DELICATE works by increasing the local SNR and improving the evenness of nuclei fluorescence intensity across cells especially in the late embryos. The method both dramatically reduces the segmentation errors by StarryNite and the time required for manually correcting tracing errors up to 550-cell stage, allowing the generation of accurate cell lineage at large-scale with a user-friendly software/interface.

All images and data are available at https://doi.org/10.6084/m9.figshare.26778475.v1. The code and user-friendly software are available at https://github.com/plcx/NucApp-develop.