SWARM resolves nanopore signal interference between RNA modification types and reveals splicing-shaped pseudouridylation.

AI framework (SWARM) deconvolving nanopore signal interference between RNA modification types (m6A, pseudouridine, m5C)

Direct RNA nanopore sequencing promises to simultaneously map multiple RNA modification types (epitranscriptome), but suffers from high false-positive rates due to signal interference between modification types. SWARM is an AI-based framework that resolves this by deconvolving overlapping signals, enabling accurate detection of m6A, pseudouridine, and m5C modifications. Applied to multi-tissue data, SWARM reveals a new mechanism: pseudouridylation is partially regulated by alternative splicing. Code is open-source.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Signal interference between modification types is the main limitation of direct RNA nanopore sequencing, hindering clinical adoption. SWARM represents a concrete technical advance that brings this technology closer to diagnostic application in epitranscriptomics. The discovery of splicing-pseudouridylation coupling opens a relevant avenue for diseases with aberrant splicing.

Clinical impact: 2/3 · Evidence strength: 3/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 8/10