REDfly: An Integrated Knowledgebase for Insect Regulatory Genomics

SIMPLE SUMMARY: Understanding how genes are regulated is a vital area of current biological research and a crucial adjunct to ongoing efforts to sequence entire genomes. Knowing the DNA sequences responsible for gene regulation—transcriptional cis-regulatory modules (CRMs, e.g., “enhancers”) and transcription factor binding sites (TFBSs)—is important for many areas of research including interpretation and validation of data developed by large-scale genomics projects, providing training data for machine-learning CRM-discovery methods, genome annotation, modeling gene-regulatory networks, studying the evolution of gene regulation, and numerous aspects of the basic biology of transcriptional regulation. Knowledge of insect CRMs is also an important step in developing biotechnology methods for control of insect disease vectors and for eliminating pathogen transmission. The REDfly (Regulatory Element Database for Fly) database integrates all of the available insect cis-regulatory information from multiple sources to provide a comprehensive collection of known regulatory elements. In this paper, we describe REDfly’s basic contents and data model, emphasizing recently added features, and provide illustrated walk-throughs of some common search scenarios. ABSTRACT: We provide here an updated description of the REDfly (Regulatory Element Database for Fly) database of transcriptional regulatory elements, a unique resource that provides regulatory annotation for the genome of Drosophila and other insects. The genomic sequences regulating insect gene expression—transcriptional cis-regulatory modules (CRMs, e.g., “enhancers”) and transcription factor binding sites (TFBSs)—are not currently curated by any other major database resources. However, knowledge of such sequences is important, as CRMs play critical roles with respect to disease as well as normal development, phenotypic variation, and evolution. Characterized CRMs also provide useful tools for both basic and applied research, including developing methods for insect control. REDfly, which is the most detailed existing platform for metazoan regulatory-element annotation, includes over 40,000 experimentally verified CRMs and TFBSs along with their DNA sequences, their associated genes, and the expression patterns they direct. Here, we briefly describe REDfly’s contents and data model, with an emphasis on the new features implemented since 2020. We then provide an illustrated walk-through of several common REDfly search use cases.