Abstract
The combination of model organisms and comprehensive genome-wide screens has provided a wealth of data into the structure and regulation of the genome, gene–environment interactions, and more recently, into the mechanism of action of human therapeutics. The success of these studies relies, in part, on the ability to quantify the combined effects of multifactorial biological interactions. In this review, we explore the history and rationale behind genetic and chemical–genetic interactions with an emphasis on the phenomena of drug synergy and then briefly describe the theoretical models that we can leverage to investigate the synergy between compounds. In addition to reviewing the literature, we also provide a reference list including many of the most important studies in this field. The concept of chemical genetics interactions derives from classical studies of synthetic lethality and functional genomics. These techniques have recently graduated from the research lab to the clinic, and a better understanding of the basic principles can help accelerate this translation.
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Abbreviations
- AIDS:
-
Acquired immunodeficiency syndrome
- AML:
-
Acute myeloid leukemia
- BarSeq:
-
Barcode sequencing
- DSB:
-
Double-strand break
- HGP:
-
Human Genome Project
- HIP:
-
Haplo-insufficiency profiling
- HOP:
-
Homozygous profiling
- HSA:
-
Highest-single agent
- MIC:
-
Minimal inhibitory concentrations
- RB-TnSeq:
-
Random bar code transposon-site sequencing
- SAR:
-
Structure–activity-relationships
- Sc:
-
Saccharomyces cerevisiae
- SGA:
-
Synthetic genetic arrayTnSeq Transposon mutagenesis coupled to next-generation sequencing
- YKO:
-
Yeast knockout
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Gaikani, H., Giaever, G., Nislow, C. (2021). Chemical–Genetic Interactions as a Means to Characterize Drug Synergy. In: Vizeacoumar, F.J., Freywald, A. (eds) Mapping Genetic Interactions. Methods in Molecular Biology, vol 2381. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1740-3_14
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