Multi-functional Genome-wide CRISPR System for High Throughput Genotype-Phenotype Mapping

Most of existing methods for genome-scale engineering are limited to a single mode of genomic alteration, i.e. overexpression, repression, or deletion. Here we develop a multi-functional genome-wide CRISPR (MAGIC) system for high throughput genotype-phenotype mapping. By combining the tri-functional CRISPR system and array-synthesized oligo pools, MAGIC was used to create the most diversified library and identify novel genetic determinants of complex phenotypes, particularly those with synergistic interactions when regulated to different expression levels.