A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer)

Nathan D. Berkowitz, Ian M. Silverman, Daniel M. Childress, Hilal Kazan, Li-San Wang, Brian D. Gregory

RNA molecules fold into complex three-dimensional shapes, guided by the pattern of hydrogen bonding between nucleotides. This pattern of base pairing, known as RNA secondary structure, is critical to their cellular function. Recently several diverse methods have been developed to assay RNA secondary structure on a transcriptome-wide scale using high-throughput sequencing. Each approach has its own strengths and caveats, however there is no widely available tool for visualizing and comparing the results from these varied methods. To address this, we have developed Structure Surfer, a database and visualization tool for inspecting RNA secondary structure in six transcriptome-wide data sets from human and mouse ( http://tesla.pcbi.upenn.edu/strucuturesurfer/ ). The data sets were generated using four different high-throughput sequencing based methods. Each one was analyzed with a scoring pipeline specific to its experimental design. Users of Structure Surfer have the ability to query individual loci as well as detect trends across multiple sites. Here, we describe the included data sets and their differences. We illustrate the database's function by examining known structural elements and we explore example use cases in which combined data is used to detect structural trends. In total, Structure Surfer provides an easy-to-use database and visualization interface for allowing users to interrogate the currently available transcriptome-wide RNA secondary structure information for mammals.