Randfold

Randfold evaluates minimum free energy of non-coding RNA secondary structures to assess folding stability and identify statistically significant structural biases.

Key Features:

• Folding Energy Calculation: Calculates minimum free energy (MFE) for secondary structures of non-coding RNAs, including microRNA precursors, tRNAs, and rRNAs across eukaryotic taxa.
• Statistical Bias Assessment: Performs randomization tests by comparing MFE of natural sequences with MFEs from randomly shuffled sequence permutations to evaluate structural bias.
• Differential Analysis Across RNA Types: Reports differential MFE patterns showing miRNA precursors often have significantly lower MFE in natural sequences compared to shuffled controls, while tRNAs and rRNAs do not show this difference.

Scientific Applications:

• Detection of Genuine miRNA Sequences: Identifies candidate miRNAs by detecting significantly lower MFE in native sequences relative to shuffled permutations, indicating predisposition to stable secondary structure.
• Comparative Structural Analysis: Compares secondary structure stability across non-coding RNA classes and eukaryotic taxa to study evolutionary conservation and functional specialization.

Methodology:

Calculate minimum free energy for input RNA sequences and perform randomization tests by comparing natural-sequence MFEs to MFEs from shuffled sequence permutations to identify significant structural biases.