R-loopBase: a knowledgebase for genome-wide R-loop formation and regulation

Abstract

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.

Systematic Evaluation of Different R-loop Mapping Methods: Achieving Consensus, Resolving Discrepancies and Uncovering Distinct Types of RNA:DNA Hybrids

“…All R-loop mapping data were processed with a uniform pipeline (see Methods). As noted previously (Halasz et al 2017; Vanoosthuyse 2018; Crossley et al 2019; Lin et al 2022), different strategies have distinct performances, resulting in variable peak number (from ∼5,000 to ∼80,000) and peak size range (from ∼200 bp to ∼1.5 kb) (Fig. 1A, B).…”

“…Future users have to carefully consider the pros and cons of individual technologies, filter out technology-specific false positive signals, and study the RNA:DNA hybrid class of your interest. Regardless of which method you have chosen, it is also a good practice to focus on consensus R-loop forming regions based on integrative analysis of existing R-loop mapping datasets (Miller et al 2021; Lin et al 2022).…”

“…Future users have to carefully consider the pros and cons of individual technologies, filter out technology-specific false positive signals, and study the RNA:DNA hybrid class of your interest. Regardless ofwhich method you have chosen, it is also a good practice to focus on consensus R-loop forming regions based on integrative analysis of existing R-loop mapping datasets(Miller et al 2021;Lin et al 2022).Theoretical consideration of typical R-loop formationR-loop formation must enlist nascent RNA transcripts to invade into DNA duplex, especially in genomic regions that contain various non-B DNA structures. There are two models for envisioning this process.…”

LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond

“…In colorectal cancer (CRC), lncRNA SATB2-AS1 directly recruits WDR5 and GADD45A, promoting SATB2 transcription by histone modification, as well as DNA demethylation [ 92 ], which inhibits cell metastasis and regulates the immune response in CRC. Recently, a database was created, with a comprehensive list of R-loops and their respective regulatory proteins [ 107 ], which might serve as a useful resource to identify novel lncRNAs with the potential to recruit GADD45A via formation of R-loops.…”

An updated overview of experimental and computational approaches to identify non-canonical DNA/RNA structures with emphasis on G-quadruplexes and R-loops

“…To deepen the understanding R-loop genome localisation and its regulatory network, the database of R-loopBase integrating R-loop distribution and regulation was developed in 2021 [ 127 ]. Through the integration of genomics and literature data, the following were included in the database: 107 high-quality genome-wide R-loop mapping datasets generated based on 11 different technologies.…”