NoBIAS: Non-coding RNA Base Interaction Annotation using Visual Snapshot

Non-coding RNAs fold into complex 3D structures that govern their biological functions, with RNA structural motifs (RSMs) serving as conserved building blocks of this architecture.
These motifs are defined by characteristic base-interaction patterns, making accurate identification and classification of RNA interactions essential for understanding RNA structure and function.

Despite their biological importance, accurately identifying and classifying these interactions remains challenging because the available data are highly variable in quality and scarce in quantity. This compromises annotation reliability, hinders the construction of trustworthy ground truth for systematic assessment, and restricts the supply of reliable training examples needed for supervised learning.

To address this, we introduce NoBIAS, the first resolution-aware, integrated machine learning-based suite for annotating base interactions from 3D RNA structures, inspired by human pattern recognition, augmented with structure prediction for data enrichment, and evaluated on a carefully curated, stratified benchmark.

NoBIAS is a hierarchical framework for RNA base-interaction annotation that integrates interaction-specific inductive biases with multimodal representation learning. By combining a convolution-augmented, rule-guided module for stacking interactions with complementary graph and image encoders for pairing interactions, NoBIAS captures both structural priors and local visual cues of RNA base doublets. A performance-calibrated logit fusion scheme then adaptively integrates modality-specific predictions based on local-structural resolution, enabling robust inference across heterogeneous 3D RNA structures.

Evaluation across multiple benchmark tiers: spanning consensus, homolog-supported, and manually verified cases, shows that NoBIAS consistently outperforms existing methods under increasingly challenging conditions. Together, the NoBIAS design and its evaluation framework provide a systematic foundation for robust RNA base-interaction annotation, enabling more reliable analysis of RNA structure under realistic uncertainty.