Franco Joseph Vizeacoumar - Mapping Genetic Interactions

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Information encoded within the genome of an organism is expressed in all aspects of the biological phenotype. However, the genotype to phenotype relationship is not straightforward and in a major way depends on complex functional interactions between genes. Mapping these genetic interactions provides clues to the understanding of the contextual functioning of genomes as the cross-talks are usually found between genes controlling overlapping responses. More recently, functional cross-talks between gene pairs took a center stage as they have an exciting potential to reveal the blueprint of the cancer genome and ultimately provide what could be defined as a Google Map of a cancer cell. Thus, genetic interactions are now emerging as a major highway for drug target identification in cancer therapeutics. To augment this approach, we are presenting in this edition 18 chapters assembled into six major categories. The first part covers methodologies used to capture genetic interactions in model organisms. This includes approaches undertaken in bacteria, yeast, worms, and flies. Part II covers strategies applied in human cells. Particularly, methods that rely on RNA interference and CRISPR/Cas9-based genome editing technologies in arrayed and pooled screening formats in both in vitro and in vivo models are much sought after, and we have covered many of them in this part. While wet lab approaches are holding a lead in mapping genetic interactions, in silico computation is also beginning to play its part in predicting genetic interactions. Some aspects of this rapidly evolving strategy are covered in the third part of the book. Apart from these powerful approaches, chemical genetic methods are also widely and successfully used to discover both novel genetic relationships and clinically relevant drug-gene interactions. In Part IV, one of the chapters is dedicated to identifying such drug-gene interactions, while another chapter provides a comprehensive overview of the approaches currently available for mapping chemical genetic interactions and identifying synergistic drug-gene relations. More recently, several emerging technologies such as single cell sequencing and gene expression profiling have been also contributing toward understanding the biological context in which genetic interactions can be modulated. Part V discusses the applicability of these advances to the discovery of novel genetic interactions. Finally, while knowing the identity of genetic interactions provides functional clues, it is not sufficient by itself to assure the development of novel effective cancer therapies. To address this, we have dedicated the last, sixth part of this book to the discussions of translation aspects that aim to identify small molecule inhibitors or protein-based inhibitors for bringing genetic relationships into the clinics.

We thank Mackenzie MacAuley and Frederick S. Vizeacoumar for assisting in formatting some of the chapters, Jeff Patrick Vizeacoumar for the cover design and our families for their patience during the preparation of this book.