Work

ReTIF: Granularity-Aware Multitask Interaction Routing for RNA-Compound Interaction Prediction and Binding-Site Localization

Year: 2026

Type: preprint

Abstract: RNA-targeted drug discovery requires both RNA–compound interaction prediction and nucleotide-level binding-site (BS) localization. These two tasks rely on different levels of interaction information: DTI prediction summarizes overall RNA-compound compatibility, whereas BS localization requires preserving nucleotide-level compound-associated signals. However, existing multitask models often use shared cross-modal representations for both tasks before task-specific prediction layers, which may limit their ability to preserve task-dependent interaction patterns. We therefore propose R e TIF( Relation-enhanced Task-specific Interaction Frame-work ), which constructs separate cross-modal interaction representations for DTI prediction and BS localization before aggregation. ReTIF integrates multi-source RNA-compound representations from frozen RNA-FM, StructRFM, Mole-BERT, and MolFormer encoders, and builds separate interaction representations for DTI scoring and BS localization. The DTI branch captures global compatibility through aggregation, whereas the BS branch preserves nucleotide-compound resolution and enhances local evidence through relation-guided propagation with RNA structural and compound topological priors. An asymmetric DTI-derived compatibility signal provides global context to BS prediction while maintaining local evidence. Across five-fold evaluations under unseen pair, RNA, compound, and joint shifts with 13 base-lines, R e TIF has the highest mean in 13 of 16 scenario-metric combinations, including BS AUPR in all four settings.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.09.02.748859