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.
%0 Journal Article
%1 Dreze2009Edgetic
%A Dreze, Matija
%A Charloteaux, Benoit
%A Milstein, Stuart
%A Vidalain, Pierre-Olivier O.
%A Yildirim, Muhammed A.
%A Zhong, Quan
%A Svrzikapa, Nenad
%A Romero, Viviana
%A Laloux, Géraldine
%A Brasseur, Robert
%A Vandenhaute, Jean
%A Boxem, Mike
%A Cusick, Michael E.
%A Hill, David E.
%A Vidal, Marc
%D 2009
%I Nature Publishing Group
%J Nature methods
%K interactome networks protein-protein-interactions
%N 11
%P 843--849
%R 10.1038/nmeth.1394
%T 'Edgetic' perturbation of a C. elegans BCL2 ortholog.
%U http://dx.doi.org/10.1038/nmeth.1394
%V 6
%X 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.
@article{Dreze2009Edgetic,
abstract = {
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.
},
added-at = {2018-12-02T16:09:07.000+0100},
author = {Dreze, Matija and Charloteaux, Benoit and Milstein, Stuart and Vidalain, Pierre-Olivier O. and Yildirim, Muhammed A. and Zhong, Quan and Svrzikapa, Nenad and Romero, Viviana and Laloux, G\'{e}raldine and Brasseur, Robert and Vandenhaute, Jean and Boxem, Mike and Cusick, Michael E. and Hill, David E. and Vidal, Marc},
biburl = {https://www.bibsonomy.org/bibtex/2577ea5c27fc3c6d92c7332ade4b167e2/karthikraman},
citeulike-article-id = {6016860},
citeulike-linkout-0 = {http://dx.doi.org/10.1038/nmeth.1394},
citeulike-linkout-1 = {http://dx.doi.org/10.1038/nmeth.1394},
citeulike-linkout-2 = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865203/},
citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19855391},
citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19855391},
day = 25,
doi = {10.1038/nmeth.1394},
interhash = {346d0b99dd913fd7896cd075400d8378},
intrahash = {577ea5c27fc3c6d92c7332ade4b167e2},
issn = {1548-7105},
journal = {Nature methods},
keywords = {interactome networks protein-protein-interactions},
month = nov,
number = 11,
pages = {843--849},
pmcid = {PMC2865203},
pmid = {19855391},
posted-at = {2009-11-27 08:54:44},
priority = {2},
publisher = {Nature Publishing Group},
timestamp = {2018-12-02T16:09:07.000+0100},
title = {'Edgetic' perturbation of a C. elegans {BCL2} ortholog.},
url = {http://dx.doi.org/10.1038/nmeth.1394},
volume = 6,
year = 2009
}