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Chemical–Genetic Interactions as a Means to Characterize Drug Synergy

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Mapping Genetic Interactions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2381))

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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Authors and Affiliations

  1. Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada

    Hamid Gaikani, Guri Giaever & Corey Nislow

  2. Department of Chemistry, University of British Columbia, Vancouver, BC, Canada

    Hamid Gaikani

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  1. Hamid Gaikani
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  2. Guri Giaever
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  3. Corey Nislow
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Correspondence to Corey Nislow .

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  1. University of Saskatchewan, Saskatoon, SK, Canada

    Franco Joseph Vizeacoumar

  2. University of Saskatchewan, Saskatoon, SK, Canada

    Andrew Freywald

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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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  • DOI: https://doi.org/10.1007/978-1-0716-1740-3_14

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