Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.
Sonnichsen B., Koski L.B., Walsh A., Marschall P., Neumann B., Brehm M., Alleaume A.M., Artelt J., Bettencourt P., Cassin E., Hewitson M., Holz C., Khan M., Lazik S., Martin C., Nitzsche B., Ruer M., Stamford J., Winzi M., Heinkel R., Roder M., Finell J., Hantsch H., Jones S.J., Jones M., Piano F., Gunsalus K.C., Oegema K., Gonczy P., Coulson A., Hyman A.A., Echeverri C.J.
A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.