SeqFold

SeqFold predicts RNA secondary structures at genome scale by integrating high-throughput RNA structure profiling data with computational ensemble sampling and classification to reconstruct transcriptome-wide RNA secondary structure.

Key Features:

• Integration of High-Throughput Data: Incorporates PARS, SHAPE-Seq, FragSeq (fragmentation sequencing), deep sequencing data, and conventional SHAPE data for structure probing inputs.
• Structure Preference Profile (SPP): Transforms experimental RNA structure information into a Structure Preference Profile (SPP) used to represent ensemble-informed structure preferences.
• High-Dimensional Classification Framework: Uses a high-dimensional classification framework to match an SPP to the most likely cluster of structures sampled from a Boltzmann-weighted ensemble.
• Performance and Robustness: Benchmarked against known structures of mRNAs and noncoding RNAs, showing comparable or superior accuracy and robustness to noisy data.
• Adaptability: Supports incorporation of new types of high-throughput RNA structure profiling data as they become available.

Scientific Applications:

• Structurome reconstruction: Reconstructs RNA secondary structures across entire transcriptomes to generate transcriptome-wide structuromes.
• Gene regulation analysis: Enables analysis of how RNA secondary structure influences translation efficiency, transcription initiation, and protein–RNA interactions.
• Yeast transcriptome studies: Applied to the yeast transcriptome to uncover diverse impacts of RNA secondary structure on translation, transcription initiation, and protein–RNA interactions.

Methodology:

Integrates PARS, SHAPE-Seq, FragSeq, deep sequencing and conventional SHAPE data into a Structure Preference Profile (SPP), samples structures from a Boltzmann-weighted ensemble, clusters sampled structures, applies a high-dimensional classification framework to match SPPs to structure clusters and selects stable structure candidates, and benchmarks predictions against known mRNA and noncoding RNA structures.