LinearRaccess: linear-time approximation of RNA accessibility without base-pair span limits
Motivation: RNA accessibility is the probability that every nucleotide in a contiguous interval is simultaneously unpaired; it is widely used to predict binding sites for RNA-binding proteins and other RNA-RNA interactions, often in the form of the opening energy, an equivalent measure on a logarithmic scale. Existing tools restrict the maximum base-pair span, discarding long-range base pairs…
RNA accessibility is a crucial metric for predicting binding sites of RNA-binding proteins and other RNA-RNA interactions. Existing tools often impose a maximum base-pair span limit, discarding long-range base pairs that are biologically significant, or rely on sampling methods which introduce statistical variance. Additionally, some tools compute RNA accessibility exactly, but at a cubic time complexity, making them computationally expensive.
To address these limitations, researchers have developed LinearRaccess, a linear-time approximation algorithm for RNA accessibility. LinearRaccess computes the accessibility of windows longer than one nucleotide deterministically, without any base-pair span restrictions, in a single pass through the sequence. It achieves this by utilizing beam-pruned inside-outside dynamic programming combined with a difference-array aggregation step.
In terms of performance, LinearRaccess runs in O(N) time complexity and O(Nb) memory, where N is the length of the RNA sequence and b is the fixed beam width. When compared to exact accessibility calculations on 12,872 bpRNA-1m(90) sequences of 100-1,000 nucleotides, LinearRaccess shows a median opening-energy error of below 0.001 kcal/mol (0.14 kcal/mol for windows of 700-1,000 nucleotides).
The algorithm's ability to distinguish windows of extremely low accessibility, including 35-nucleotide windows, further highlights its precision.
The researchers tested LinearRaccess on the full SARS-CoV-2 genome, which contains 29,903 nucleotides, and completed the analysis in just 419 seconds. This demonstrates the practicality and efficiency of LinearRaccess for large-scale RNA accessibility studies.
In conclusion, LinearRaccess represents a significant advancement in RNA accessibility computation. It is the first method to compute the accessibility of windows longer than one nucleotide deterministically (without sampling) in linear time without imposing any base-pair span limits. The availability of LinearRaccess through its GitHub repository (https://github.com/TakumiOtagaki/LinearRaccess) and Zenodo archive (https://doi.org/10.5281/zenodo.23598502) ensures that researchers can easily access and utilize this powerful tool for their RNA accessibility analyses.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
