A high-throughput approach to profile RNA structure

Delli Ponti, Riccardo, 1987-; Marti, Stefanie; Armaos, Alexandros, 1989-; Tartaglia, Gian Gaetano

doi:http://dx.doi.org/10.1093/nar/gkw1094

A high-throughput approach to profile RNA structure

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Citació

Delli Ponti R, Marti S, Armaos A, Tartaglia GG. A high-throughput approach to profile RNA structure. Nucleic Acids Res. 2017 Mar 17;45(5):e35. DOI: 10.1093/nar/gkw1094

Resum

Here we introduce the Computational Recognition of Secondary Structure (CROSS) method to calculate the structural profile of an RNA sequence (single- or double-stranded state) at single-nucleotide resolution and without sequence length restrictions. We trained CROSS using data from high-throughput experiments such as Selective 2΄-Hydroxyl Acylation analyzed by Primer Extension (SHAPE; Mouse and HIV transcriptomes) and Parallel Analysis of RNA Structure (PARS; Human and Yeast transcriptomes) as well as high-quality NMR/X-ray structures (PDB database). The algorithm uses primary structure information alone to predict experimental structural profiles with >80% accuracy, showing high performances on large RNAs such as Xist (17 900 nucleotides; Area Under the ROC Curve AUC of 0.75 on dimethyl sulfate (DMS) experiments). We integrated CROSS in thermodynamics-based methods to predict secondary structure and observed an increase in their predictive power by up to 30%.