A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

Abstract

This study defines a network of synthetic sick/lethal interactions with a set of query genes in a series of isogenic cancer cell lines. Analysis of differential essentiality reveals general properties in genetic interaction networks derived from studies on model organisms.

Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles

“…However, our siRNA knockdown validation experiments gave complementary support for the essentiality of the predicted kinases. As a future development, it might be useful to combine the chemical and RNAi-based perturbation experiments with genomic analyses to provide improved identification of molecular addictions and co-dependencies, along the lines suggested in recent integrative studies (Gatza et al, 2014;Sundaramurthy et al, 2014;Vizeacoumar et al, 2013).…”

Decoding directional genetic dependencies through orthogonal CRISPR/Cas screens

“…We demonstrate how this approach can be used to accurately quantify gene activation and knockout phenotypes as well as combinations thereof, to interpret orientation in activating genetic interactions, simply by expressing two sgRNAs, a task that would have been incredibly challenging to achieve before the advent of CRISPR/Cas technology. Moreover, the orthogonal screening approach developed here significantly advances previous approaches that characterise genetic interactions in mammalian cells by means of RNAi [13][14][15]17 and complements more recently published symmetric CRISPR/Cas knockout based screening approaches 63 . It also opens the door to combinations of any two CRISPR/Cas-based technologies, such as transcriptional silencing 64 or targeted DNA methylation 65 , which represents a substantial advance compared to the only other orthogonal CRISPR/Cas-based method published to date by Dahlmann et al, which achieves gene activation and knockout using 'catalytically dead' sgRNAs in combination with a catalytically active CRISPRa Cas9 enzyme from S.pyogenes 66 .…”

Gonadal transcriptome analysis of wild contaminated female European eels during artificial gonad maturation

“…The kinectin gene (ktn1) is involved in the transport of various cellular organelles and vesicles along the microtubules in the cytoplasm. Despite the paucity of research on the zc3h13 gene, one article by Vizeacoumar et al (2013) shows that it plays a key role in chromosome segregation during the cell cycle. Overall, the genes that appeared associated to GSI in this study are generally involved in mitotic cell division.…”