Abstract

BackgroundRecent advances in RNA structure probing technologies, including the ones based on high-throughput sequencing, have improved the accuracy of thermodynamic folding with quantitative nucleotide-resolution structural information.ResultsIn this paper, we present a novel approach, ProbeAlign, to incorporate the reactivities from high-throughput RNA structure probing into ncRNA homology search for functional annotation. To reduce the overhead of structure alignment on large-scale data, the specific pairing patterns in the query sequences are ignored. On the other hand, the partial structural information of the target sequences embedded in probing data is retrieved to guide the alignment. Thus the structure alignment problem is transformed into a sequence alignment problem with additional reactivity information. The benchmark results show that the prediction accuracy of ProbeAlign outperforms filter-based CMsearch with high computational efficiency. The application of ProbeAlign to the FragSeq data, which is based on genome-wide structure probing, has demonstrated its capability to search ncRNAs in a large-scale dataset from high-throughput sequencing.ConclusionsBy incorporating high-throughput sequencing-based structure probing information, ProbeAlign can improve the accuracy and efficiency of ncRNA homology search. It is a promising tool for ncRNA functional annotation on genome-wide datasets.AvailabilityThe source code of ProbeAlign is available at http://genome.ucf.edu/ProbeAlign.

Highlights

  • Recent advances in RNA structure probing technologies, including the ones based on highthroughput sequencing, have improved the accuracy of thermodynamic folding with quantitative nucleotideresolution structural information

  • Availability: The source code of ProbeAlign is available at http://genome.ucf.edu/ProbeAlign

  • The difficulty of ncRNA annotation is partly due to the computational overhead of structure alignment, and partly due to the low information content given by the secondary structures [22]

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Summary

Introduction

Recent advances in RNA structure probing technologies, including the ones based on highthroughput sequencing, have improved the accuracy of thermodynamic folding with quantitative nucleotideresolution structural information. Genome-wide annotation of known ncRNA families by homology search still appears as an open problem for lacking efficient and accurate computational pipelines. The latest release of the widely used software CMsearch has significantly improved the computational efficiency of its previous versions [20]. It still would take about 3 hours to annotate the 1 Gbp chicken genome with known Rfam [21] families on a 100-CPU cluster even with filters and MPI applied [20]. The difficulty of ncRNA annotation is partly due to the computational overhead of structure alignment, and partly due to the low information content given by the secondary structures [22]

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