Pooled RNAi selection platform maps genetic modifiers of gene knockdown across hundreds of C. elegans backgrounds

Researchers have posted a preprint on bioRxiv describing a pooled screening platform designed to identify genetic modifiers of RNA interference (RNAi) knockdown effects in Caenorhabditis elegans at a scale previously impractical with individual-isolate approaches.

Studying genetic interactions — where the effect of disrupting one gene depends on variants elsewhere in the genome — has typically required either constructing large panels of individual mutant lines or screening isolates one at a time. The new platform uses RNAi by feeding (a standard C. elegans technique in which bacteria expressing double-stranded RNA targeting a gene of interest are fed directly to worms) combined with pooled culture of hundreds of natural isolates. Whole-genome sequencing of the pool before and after selection is then used to quantify relative fitness of each genetic background under each knockdown condition, yielding a genome-wide map of modifier loci.

The authors applied the method across many genetic backgrounds and RNAi conditions, generating data on how natural sequence variation modulates the fitness consequences of individual gene knockdowns. The approach sidesteps the need to construct individual mutant lines and should make it feasible to examine modifier landscapes for a large number of essential or semi-essential genes.

The work is a preprint and has not yet been peer-reviewed. As a study in a model invertebrate, its findings speak primarily to fundamental questions in quantitative and population genetics, and to researchers developing functional-genomic tools in C. elegans. No human clinical relevance is claimed by the authors.