Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans

By B. Sönnichsen, L. Koski, A. Walsh, P. Marschall, Beate Neumann, M. Brehm, Anne-Marie Alleaume, J. Artelt, Paulo Bettencourt, Etienne Cassin and 22 more. Nature, 2005

933 citations recorded by the source corpus.

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.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8aedb0a9c839ba8eb1bc9f9b69b010dc7b7af2f5

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Citations in the corpus

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases (2011, background): “and knockdown of this protein is embryonic lethal in the worm (343).”
The world of protein acetylation. (2016, background): “sults in lethality for Drosophila melanogaster [79], Trypanosoma brucei [80] as well as Caenorhabditis elegans [81].”
The pleiotropic structure of the genotype–phenotype map: the evolvability of complex organisms (2011, methodology): “For instance, the knockdown strategy has been used to assess pleiotropy of genes that function in early nematode embryogenesi”
Visualization of image data from cells to organisms (2010, neutral): “Some large-scale experiments involving particularly complex read-outs have been annotated manually using controlled vocabularies 51 , in some cases—as for high-content analysis of gene expression during development—eased by the use of custom-built annotation tools 34,52,53 .”
Finding function in novel targets: C. elegans as a model organism (2006, background): “elegans , as most RNAi knockdown phenotypes can be reproduced with the corresponding gene knockou”
Controlling morpholino experiments: don't stop making antisense (2008, background): “…such as X. tropicalis (Rana et al., 2006), that have been done successfully using RNAi in C. elegans embryos (Gonczy et al., 2000; Kamath et al., 2003; Sonnichsen et al., 2005) and in tissue culture cells in D. melanogaster (Agaisse et al., 2005; Boutros et al., 2004; Friedman and Perrimon, 2006).”