Mapping Genetic Interactions

This volume details methods of identifying synthetic lethal, genetic interactions by various approaches in different model systems including human cancer cells. Chapters guide readers through genetic interactions in model organisms, RNA interference, CRISPR/Cas9 based genome editing technologies, drug-gene interactions, mapping chemical genetic interactions, synergistic drug-gene relations, single cell sequencing, gene expression profiling, and novel genetic interactions. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols.

 

Authoritative and cutting-edge, Genetic Interaction Mapping aims to be a useful practical guide to researches to help further their study in this field.

Part I: Mapping Genetic Interactions in Model Systems

1. Quantitative Genetic Screens for Mapping Bacterial Pathways and Functional Networks

Alla Gagarinova, Ali Hosseinnia, and Mohan Babu

 

2. Mapping Synthetic Dosage Lethal Genetic Interactions in Saccharomyces cerevisiae

Akil Hamza, Leanne Amitzi, Supipi Duffy, and Philip Hieter

 

3. Systematic High-Content Screening of Fluorescently-Tagged Yeast Double Mutant Strains

Harsha Garadi Suresh and Mojca Mattiazzi Usaj

 

4. A Genetic Interaction Screening Approach in C. elegans

John A. Calarco

 

5. RNA Interference (RNAi) Screening in Cultured Drosophila Cells

Juan-Carlos A. Padilla, Ashley Chin, Dhara Patel, Xiaofeng Wang, Philippe Jolivet, and Eric Lécuyer

 

 

Part II: Approaches to Map Genetic Interactions in Human cells

6. Employing Cross-Species Approaches to Construct Humanized Genetic Interaction Networks

Lucile M. Jeusset and Kirk J. McManus

 

7. Identification of Synthetic Lethal Interactions Using High-Throughput, Arrayed CRISPR/Cas9-based Platforms

Mackenzie J. MacAuley, Omar Abuhussein, and Frederick S. Vizeacoumar

 

8. Exploring Candidate Human Synthetic Lethal Interactions Through siRNA and Quantitative Imaging-Based Approaches

Lucile M. Jeusset and Kirk J. McManus

 

9. Mapping Genetic Interactions in Human Cancer Cells Using a One-Step tRNA-CRISPR System
Derek Yisen Zhang, Xiong Gui, and Xiaolong Yang

 

10. In vivo Genome-Wide Pooled RNAi Screens in Cancer Cells to Identify Determinants of Chemotherapy/Drug Response

Margaret L Dahn and Paola Marcato

 

Part III: Predicting Genetic Interactions Using Computational Approaches

11. INCISOR: An Algorithm to Identify Synthetic Rescue Mediators of Resistance to Targeted and Immunotherapy

Xiaoman Wang, Frederick Sagayaraj Vizeacoumar, and Avinash Das Sahu

  12. Machine Learning to Identify Gene Interactions from High-Throughput Mutant Crosses

Ashwani Kumar, Andrew Cameron, and Sandra Zilles

 

13. Identification of Drug Resistance Genes Using a Pooled Lentiviral CRISPR/Cas9 Screening Approach

Evan M. Kerek, Christopher R. Cromwell, and Basil P. Hubbard

 

14. Chemical Genetic Interactions as a Means to Characterize Drug Synergy

Hamid Gaikani, Guri Giaever, and Corey Nislow

 

 

Part V: Emerging Technologies that Leverage Mapping Genetic Interactions

15. Puromycin Labeling Coupled with Proximity Ligation Assays to Define Sites of mRNA Translation in Drosophila Embryos and Human Cells

Ashley Chin and Eric Lécuyer

 

16. Inferring Copy Number from Triple Negative Breast Cancer Patient Derived Xenograft scRNAseq Data using scCNAutils

Elena Kuzmin, Jean Monlong, Constanza Martinez Ramirez, Hellen Kuasne, Claudia L. Kleinman, Jiannis Ragoussis, Guillaume Bourque, and Morag Park

 

Part VI: Downstream Validation of Genetic Interactions using Protein Inhibitors and Small Molecules

 

17. Generation of Protein Inhibitors for Validation of Cancer Drug Targets Identified in Functional Genomic Screens

Sherin McDonald, Arunkumar Annan Sudarsan, Hanan Babeker, Kiranmayee Budharaju, and Maruti Uppalapati

 

18. Computational Prediction of Chemical Tools for Identification and Validation of Synthetic Lethal Interaction Networks

Kalpana K Bhanumathy, Omar Abuhussein, Frederick S. Vizeacoumar, Andrew Freywald, Franco J. Vizeacoumar, Christopher P. Phenix, Eric W. Price, and Ran Cao