Review abstract
Nature Chemical Biology 4, 674 - 681 (2008)
Published online: 20 October 2008 | doi:10.1038/nchembio.120
Combination chemical genetics
Joseph Lehár1,2, Brent R Stockwell3, Guri Giaever4,5,6 & Corey Nislow4,6,7
Abstract
Predicting the behavior of living organisms is an enormous challenge given their vast complexity. Efforts to model biological systems require large datasets generated by physical binding experiments and perturbation studies. Genetic perturbations have proven important and are greatly facilitated by the advent of comprehensive mutant libraries in model organisms. Small-molecule chemical perturbagens provide a complementary approach, especially for systems that lack mutant libraries, and can easily probe the function of essential genes. Though single chemical or genetic perturbations provide crucial information associating individual components (for example, genes, proteins or small molecules) with pathways or phenotypes, functional relationships between pathways and modules of components are most effectively obtained from combined perturbation experiments. Here we review the current state of and discuss some future directions for 'combination chemical genetics', the systematic application of multiple chemical or mixed chemical and genetic perturbations, both to gain insight into biological systems and to facilitate medical discoveries.
- CombinatoRx Incorporated, 245 First Street, Cambridge, Massachusetts 02142, USA.
- Boston University Bioinformatics, 20 Cummington Street, Boston, Massachusetts 02215, USA.
- Columbia University, Department of Biological Sciences and Department of Chemistry, 614 Fairchild Center, MC2406, 1212 Amsterdam Avenue, New York, New York 10027, USA.
- Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
- Department of Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, Ontario M5S 3E1, Canada.
- Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Room 4396, Toronto, Ontario M5S 1A8, Canada.
- Banting and Best Department of Medical Research, University of Toronto, 144 College Street, Toronto, Ontario M5S 3E1, Canada.
Correspondence to: Joseph Lehár1,2 e-mail: jlehar@combinatorx.com
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