Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements

Transcriptome profiling quantitatively measures gene expression genome-wide. There is widespread interest in using transcriptomic profiles as phenotypes for epistasis analysis. Though epistasis measurements can be performed using individual transcripts, this results in many scores that must be interpreted independently. We developed a statistic that summarizes these measurements, simplifying analysis. Moreover, epistasis analysis has previously only been performed on cDNA extracted from single cells. We show that whole-organism RNA-sequencing (RNA-seq) can be used to characterize interactions between genes. With the advent of genome engineering, mutants can be created easily in many organisms. Thus, phenotyping is now the rate-limiting step toward reconstructing interaction networks. Our work potentially represents a solution to this problem because RNA-seq is sensitive to a variety of genetic perturbations.