期刊
NATURE METHODS
卷 6, 期 11, 页码 843-U89出版社
NATURE RESEARCH
DOI: 10.1038/NMETH.1394
关键词
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资金
- US National Institutes of Health (NIH), National Human Genomics Research Institute (NHGRI) and National Institute of General Medical Sciences (NIGMS) [HG001715]
- US National Cancer Institute (NCI) [R33 CA105405, R33 CA132073, R21/R33 CA081658, U01 CA105423]
- Dana-Farber Cancer Institute Strategic Initiative
- Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium)
- Federal Office for Scientific, Technical and Cultural Affairs [IAP P6/19 PROFUSA]
- NIH National Research Service [T32CA09361]
- European Molecular Biology Organization [61-2002]
- Leukemia Research Foundation
- 'Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium)'
Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward.
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