DUETT

DUETT detects and quantitatively identifies known and novel events in nascent RNA structural dynamics from high-throughput nucleotide-resolution cotranscriptional chemical probing data.

Key Features:

• Quantitative Detection: Provides an automated, systematic approach to detect RNA folding events from large high-throughput nucleotide-resolution chemical probing datasets.
• Feedback Control-Inspired Methodology: Implements a feedback control-inspired detection algorithm combined with linear regression approaches to identify structural transitions in cotranscriptional chemical probing datasets.
• Tunable Parameter Thresholds: Uses independently tunable parameter thresholds that align qualitative expectations with quantitative event calls to adjust sensitivity and specificity.
• Validation on Specific RNAs: Validated by identifying known cotranscriptional folding transitions in Escherichia coli signal recognition particle RNA and the Bacillus cereus crcB fluoride riboswitch, and by revealing heightened reactivity patterns preceding base-pair rearrangements.
• Sensitivity Analysis: Includes sensitivity analysis to evaluate tradeoffs when choosing parameter thresholds.
• Broad Applicability: Applicable across diverse cotranscriptional RNA folding contexts due to its tunable detection framework.

Scientific Applications:

• Cotranscriptional Folding Analysis: Quantitatively characterizes nascent RNA structural dynamics during transcription using nucleotide-resolution chemical probing data.
• Riboswitch and SRP Studies: Detects and maps folding transitions in riboswitches and signal recognition particle RNAs, exemplified by the crcB fluoride riboswitch and Escherichia coli SRP RNA.
• Hypothesis Generation: Generates testable hypotheses about RNA folding trajectories and transition events for further experimental validation.

Methodology:

Computational methods include a feedback control-inspired detection algorithm combined with linear regression approaches, independently tunable parameter thresholds for event calling, and sensitivity analysis to assess parameter tradeoffs.