R-loops play versatile roles in many physiological and pathological processes, and are of great interest to scientists in multiple fields. However, controversy about their genomic localization and incomplete understanding of their regulatory network raise great challenges for R-loop research. Here, we present R-loopBase (https://rloopbase.nju.edu.cn) to tackle these pressing issues by systematic integration of genomics and literature data. First, based on 107 high-quality genome-wide R-loop mapping datasets generated by 11 different technologies, we present a reference set of human R-loop zones for high-confidence R-loop localization, and spot conservative genomic features associated with R-loop formation. Second, through literature mining and multi-omics analyses, we curate the most comprehensive list of R-loop regulatory proteins and their targeted R-loops in multiple species to date. These efforts help reveal a global regulatory network of R-loop dynamics and its potential links to the development of cancers and neurological diseases. Finally, we integrate billions of functional genomic annotations, and develop interactive interfaces to search, visualize, download and analyze R-loops and R-loop regulators in a well-annotated genomic context. R-loopBase allows all users, including those with little bioinformatics background to utilize these data for their own research. We anticipate R-loopBase will become a one-stop resource for the R-loop community.
