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.
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We thank M. Srayko, C. Cowan, L. Pelletier and W. B. Wood for critical reading of the manuscript, and M. Volkmer and S. Schloissnig for their help on the completion of the online Phenobank database. This work was supported in part by the German government through a DLR grant. A.C. was supported by the MRC, UK.
The authors declare that they have no competing financial interests.
Phenotypic and functional classification of all genes with early embryonic (DIC) phenotypes. (XLS 337 kb)
Comparison between RNAi and conventional genetics. (XLS 26 kb)
Comparison of screening coverage and detection accuracy for early embryonic phenotypes in the present study versus Zipperlen et al. and Piano et al. (XLS 25 kb)
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Sönnichsen, B., Koski, L., Walsh, A. et al. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462–469 (2005). https://doi.org/10.1038/nature03353
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