Systems Biology Seminars | Ryan Baugh, Assistant Professor of Biology, Duke University | Quantification of gene function and genetic interactions genome-wide in the worm

We are developing a method to use deep sequencing for high-throughput, quantitative analysis of gene function genome-wide in C. elegans. Deep sequencing applications currently include genome sequencing, gene expression analysis, and protein:nucleic acid binding. However, these applications are descriptive in nature, at best measuring correlates of gene function. Forward genetic analysis is an extremely powerful approach to discovering gene function. However, this approach is laborious and time consuming, and it identifies individual genes with strong phenotypic effects but does not provide a quantitative overview of gene function. We are developing an approach based on transposon-mediated insertional mutagenesis, selection of large populations for the phenotype of interest, and deep sequencing of transposon insertion sites at the population level. This approach will allow us to measure mutant allele frequencies as a function of phenotype for every gene. It will also allow us to measure genetic interactions (epistasis) by starting with various mutants in the background. I will discuss the challenges we face in developing this approach, how we plan to apply it, and a theoretical framework regarding modularity of epistasis networks.