DUETT

DUETT (Detection of Unknown Events with Tunable Thresholds) is a software tool automatically identifying RNA structural transitions from high-throughput chemical probing experiments that study cotranscriptional RNA folding. These experiments generate nucleotide-resolution 'reactivities' for each length of a growing nascent RNA, reflecting its structural dynamics.

Key features of DUETT:

1. Employs a feedback control-inspired method and a linear regression approach to identify RNA folding events.

2. Relies on interpretable and independently tunable parameter thresholds, allowing users to match their qualitative expectations with quantitatively identified folding events.

3. Reduces human bias and error, standardizes event discovery, and generates hypotheses about RNA folding trajectories for further analysis and experimental validation.

4. Validated by identifying known RNA structural transitions within the cotranscriptional folding pathways of the Escherichia coli signal recognition particle RNA and the Bacillus cereus crcB fluoride riboswitch.

5. Identifies previously overlooked features in datasets, such as heightened reactivity patterns in the signal recognition particle RNA about 12 nt lengths before base-pair rearrangement.

6. Allows sensitivity analysis to identify tradeoffs when choosing parameter thresholds.

7. Tunable across a wide range of contexts, enabling flexible application to study broad classes of RNA folding mechanisms.