Annotating the Insect Regulatory Genome

Simple Summary Insects comprise the largest and most diverse class of animals on earth, and have major impacts on human health and agriculture. The effort to better understand insect biology has led to the sequencing of hundreds of insect genomes. However, the usefulness of having a genome sequence is limited in the absence of a comprehensive annotation-a description of the function of each part of the sequence. Functional parts of the genome include not only genes, but also regulatory sequences that mediate gene expression. We discuss here methods used to identify regulatory sequences within the genome, with the emphasis on a pair of tools we have developed, REDfly and SCRMshaw, that can be used in tandem to carry out this task in an efficient and economical manner. An ever-growing number of insect genomes is being sequenced across the evolutionary spectrum. Comprehensive annotation of not only genes but also regulatory regions is critical for reaping the full benefits of this sequencing. Driven by developments in sequencing technologies and in both empirical and computational discovery strategies, the past few decades have witnessed dramatic progress in our ability to identify cis-regulatory modules (CRMs), sequences such as enhancers that play a major role in regulating transcription. Nevertheless, providing a timely and comprehensive regulatory annotation of newly sequenced insect genomes is an ongoing challenge. We review here the methods being used to identify CRMs in both model and non-model insect species, and focus on two tools that we have developed, REDfly and SCRMshaw. These resources can be paired together in a powerful combination to facilitate insect regulatory annotation over a broad range of species, with an accuracy equal to or better than that of other state-of-the-art methods.