Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 311 (5766): 1481-1484

Copyright © 2006 by the American Association for the Advancement of Science

Genome-Wide Prediction of C. elegans Genetic Interactions

Weiwei Zhong, and Paul W. Sternberg*

Abstract: To obtain a global view of functional interactions among genes in a metazoan genome, we computationally integrated interactome data, gene expression data, phenotype data, and functional annotation data from three model organisms—Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster—and predicted genome-wide genetic interactions in C. elegans. The resulting genetic interaction network (consisting of 18,183 interactions) provides a framework for system-level understanding of gene functions. We experimentally tested the predicted interactions for two human disease-related genes and identified 14 new modifiers.

Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

* To whom correspondence should be addressed. E-mail: pws{at}

Systematic genetics swims forward elegantly.
Y. Suzuki and F. P. Roth (2014)
Mol Syst Biol 2, 48
   Full Text »    PDF »
Prediction of phenotype and gene expression for combinations of mutations.
G. W. Carter, S. Prinz, C. Neou, J. P. Shelby, B. Marzolf, V. Thorsson, and T. Galitski (2014)
Mol Syst Biol 3, 96
   Abstract »    Full Text »    PDF »
Network Analysis Identifies an HSP90-Central Hub Susceptible in Ovarian Cancer.
H. Liu, F. Xiao, I. G. Serebriiskii, S. W. O'Brien, M. A. Maglaty, I. Astsaturov, S. Litwin, L. P. Martin, D. A. Proia, E. A. Golemis, et al. (2013)
Clin. Cancer Res. 19, 5053-5067
   Abstract »    Full Text »    PDF »
Mextli Is a Novel Eukaryotic Translation Initiation Factor 4E-Binding Protein That Promotes Translation in Drosophila melanogaster.
G. Hernandez, M. Miron, H. Han, N. Liu, J. Magescas, G. Tettweiler, F. Frank, N. Siddiqui, N. Sonenberg, and P. Lasko (2013)
Mol. Cell. Biol. 33, 2854-2864
   Abstract »    Full Text »    PDF »
Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein G{alpha}q signaling.
H. Yu, B. Aleman-Meza, S. Gharib, M. K. Labocha, C. J. Cronin, P. W. Sternberg, and W. Zhong (2013)
PNAS 110, 11940-11945
   Abstract »    Full Text »    PDF »
Identifying proteins controlling key disease signaling pathways.
A. Gitter and Z. Bar-Joseph (2013)
Bioinformatics 29, i227-i236
   Abstract »    Full Text »    PDF »
Transcription factor redundancy and tissue-specific regulation: Evidence from functional and physical network connectivity.
S. G. Kuntz, B. A. Williams, P. W. Sternberg, and B. J. Wold (2012)
Genome Res. 22, 1907-1919
   Abstract »    Full Text »    PDF »
MIG-15 and ERM-1 promote growth cone directional migration in parallel to UNC-116 and WVE-1.
J. Teuliere, C. Gally, G. Garriga, M. Labouesse, and E. Georges-Labouesse (2011)
Development 138, 4475-4485
   Abstract »    Full Text »    PDF »
Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/{beta}-catenin signaling.
J. D. Berndt, A. Aoyagi, P. Yang, J. N. Anastas, L. Tang, and R. T. Moon (2011)
J. Cell Biol. 194, 737-750
   Abstract »    Full Text »    PDF »
Prediction of human protein-protein interaction by a mixed Bayesian model and its application to exploring underlying cancer-related pathway crosstalk.
Y. Xu, W. Hu, Z. Chang, H. DuanMu, S. Zhang, Z. Li, Z. Li, L. Yu, and X. Li (2011)
J R Soc Interface 8, 555-567
   Abstract »    Full Text »    PDF »
Selective sweeps and parallel mutation in the adaptive recovery from deleterious mutation in Caenorhabditis elegans.
D. R. Denver, D. K. Howe, L. J. Wilhelm, C. A. Palmer, J. L. Anderson, K. C. Stein, P. C. Phillips, and S. Estes (2010)
Genome Res. 20, 1663-1671
   Abstract »    Full Text »    PDF »
A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing.
C. Cantacessi, A. R. Jex, R. S. Hall, N. D. Young, B. E. Campbell, A. Joachim, M. J. Nolan, S. Abubucker, P. W. Sternberg, S. Ranganathan, et al. (2010)
Nucleic Acids Res. 38, e171
   Abstract »    Full Text »    PDF »
Predicting genetic modifier loci using functional gene networks.
I. Lee, B. Lehner, T. Vavouri, J. Shin, A. G. Fraser, and E. M. Marcotte (2010)
Genome Res. 20, 1143-1153
   Abstract »    Full Text »    PDF »
Regulators of the Actin Cytoskeleton Mediate Lethality in a Caenorhabditis elegans dhc-1 Mutant.
A. J. Gil-Krzewska, E. Farber, E. A. Buttner, and C. P. Hunter (2010)
Mol. Biol. Cell 21, 2707-2720
   Abstract »    Full Text »    PDF »
Prediction of human functional genetic networks from heterogeneous data using RVM-based ensemble learning.
C.-C. Wu, S. Asgharzadeh, T. J. Triche, and D. Z. D'Argenio (2010)
Bioinformatics 26, 807-813
   Abstract »    Full Text »    PDF »
Mitochondrial Dysfunction Confers Resistance to Multiple Drugs in Caenorhabditis elegans.
I. O. Zubovych, S. Straud, and M. G. Roth (2010)
Mol. Biol. Cell 21, 956-969
   Abstract »    Full Text »    PDF »
On the Classification of Epistatic Interactions.
H. Gao, J. M. Granka, and M. W. Feldman (2010)
Genetics 184, 827-837
   Abstract »    Full Text »    PDF »
Global networks of functional coupling in eukaryotes from comprehensive data integration.
A. Alexeyenko and E. L.L. Sonnhammer (2009)
Genome Res. 19, 1107-1116
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology.
M. C. K. Leung, P. L. Williams, A. Benedetto, C. Au, K. J. Helmcke, M. Aschner, and J. N. Meyer (2008)
Toxicol. Sci. 106, 5-28
   Abstract »    Full Text »    PDF »
Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging.
X. Cui, L. M. Lee, X. Heng, W. Zhong, P. W. Sternberg, D. Psaltis, and C. Yang (2008)
PNAS 105, 10670-10675
   Abstract »    Full Text »    PDF »
Genetic networks for the functional study of genomes.
A. G. Pisabarro, G. Perez, J. L. Lavin, and L. Ramirez (2008)
Briefings in Functional Genomics 7, 249-263
   Abstract »    Full Text »    PDF »
CressExpress: A Tool For Large-Scale Mining of Expression Data from Arabidopsis.
V. Srinivasasainagendra, G. P. Page, T. Mehta, I. Coulibaly, and A. E. Loraine (2008)
Plant Physiology 147, 1004-1016
   Abstract »    Full Text »    PDF »
Studying gene function in Caenorhabditis elegans using RNA-mediated interference.
E. M. Maine (2008)
Briefings in Functional Genomics 7, 184-194
   Abstract »    Full Text »    PDF »
Network-guided genetic screening: building, testing and using gene networks to predict gene function.
B. Lehner and I. Lee (2008)
Briefings in Functional Genomics 7, 217-227
   Abstract »    Full Text »    PDF »
Fitting a geometric graph to a protein-protein interaction network.
D. J. Higham, M. Rasajski, and N. Przulj (2008)
Bioinformatics 24, 1093-1099
   Abstract »    Full Text »    PDF »
Just Noticeable Differences in Component Concentrations Modify the Odor Quality of a Blending Mixture.
E. Le Berre, N. Beno, A. Ishii, C. Chabanet, P. Etievant, and T. Thomas-Danguin (2008)
Chem Senses 33, 389-395
   Abstract »    Full Text »    PDF »
Perturbed desmosomal cadherin expression in grainy head-like 1-null mice.
T. Wilanowski, J. Caddy, S. B. Ting, N. R. Hislop, L. Cerruti, A. Auden, L.-L. Zhao, S. Asquith, S. Ellis, R. Sinclair, et al. (2008)
EMBO J. 27, 886-897
   Abstract »    Full Text »    PDF »
Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model.
S. Hamamichi, R. N. Rivas, A. L. Knight, S. Cao, K. A. Caldwell, and G. A. Caldwell (2008)
PNAS 105, 728-733
   Abstract »    Full Text »    PDF »
CMGSDB: integrating heterogeneous Caenorhabditis elegans data sources using compositional data mining.
A. Pati, Y. Jin, K. Klage, R. F. Helm, L. S. Heath, and N. Ramakrishnan (2008)
Nucleic Acids Res. 36, D69-D76
   Abstract »    Full Text »    PDF »
Identification of BRAF as a new interactor of PLC{varepsilon}1, the protein mutated in nephrotic syndrome type 3.
H. Chaib, B. E. Hoskins, S. Ashraf, M. Goyal, R. C. Wiggins, and F. Hildebrandt (2008)
Am J Physiol Renal Physiol 294, F93-F99
   Abstract »    Full Text »    PDF »
WormBase 2007.
A. Rogers, I. Antoshechkin, T. Bieri, D. Blasiar, C. Bastiani, P. Canaran, J. Chan, W. J. Chen, P. Davis, J. Fernandes, et al. (2008)
Nucleic Acids Res. 36, D612-D617
   Abstract »    Full Text »    PDF »
Automated data integration for developmental biological research.
W. Zhong and P. W. Sternberg (2007)
Development 134, 3227-3238
   Abstract »    Full Text »    PDF »
Modelling genotype-phenotype relationships and human disease with genetic interaction networks.
B. Lehner (2007)
J. Exp. Biol. 210, 1559-1566
   Abstract »    Full Text »    PDF »
Revisiting the Krogh Principle in the post-genome era: Caenorhabditis elegans as a model system for integrative physiology research.
K. Strange (2007)
J. Exp. Biol. 210, 1622-1631
   Abstract »    Full Text »    PDF »
Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3.
A.-J. Rodrigues, G. Coppola, C. Santos, M. d. C. Costa, M. Ailion, J. Sequeiros, D. H. Geschwind, and P. Maciel (2007)
FASEB J 21, 1126-1136
   Abstract »    Full Text »    PDF »
Plasticity of genetic interactions in metabolic networks of yeast.
R. Harrison, B. Papp, C. Pal, S. G. Oliver, and D. Delneri (2007)
PNAS 104, 2307-2312
   Abstract »    Full Text »    PDF »
A systematic RNA interference screen reveals a cell migration gene network in C. elegans.
E. J. Cram, H. Shang, and J. E. Schwarzbauer (2006)
J. Cell Sci. 119, 4811-4818
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882