Selecting genes for analysis using historically contingent progress: from RNA changes to protein-protein interactions

Abstract

Progress in biology has generated numerous lists of genes that share some property. But, advancing from the initial implication of a set of genes in a process to understanding their roles in the process is slow and unsystematic. Here we use RNA silencing in C. elegans to illustrate a general approach for comparing lists of data accumulated by a field to prioritize genes for detailed study given limited resources. The partially subjective relationships between genes forged by both functional relatedness of the genes and biased progress in the field was captured as historical mutual information (HMI) and used as a quantitative measure for clustering genes. These clusters suggest regulatory links connecting RNA silencing with other processes like the cell cycle and identify understudied regulated genes that could be used to sense perturbation or mediate feedback inhibition.