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Briefings in Bioinformatics
Article . 2026 . Peer-reviewed
License: CC BY NC
Data sources: Crossref
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PubMed Central
Article . 2026
License: CC BY NC
Data sources: PubMed Central
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CircRM: profiling circular RNA modifications from nanopore direct RNA sequencing

Authors: Jiayi Li; Shenglun Chen; Zhixing Wu; Haozhe Wang; Rong Xia; Jia Meng; Yuxin Zhang;

CircRM: profiling circular RNA modifications from nanopore direct RNA sequencing

Abstract

Abstract Circular RNA (circRNA) represents a critical class of regulatory RNAs with distinctive structural and functional features. The functions of circRNAs are modulated by various RNA modifications. Here, we present CircRM, a nanopore direct RNA sequencing-based computational method for profiling RNA modifications in circRNAs at single-base and single-molecule resolution. By integrating circRNA detection, read-level modification detection, and quantitative assessment of methylation rates, CircRM identified 427 high-confidence circRNAs and enables systematic characterization of three major modifications, m5C (AUC = 0.855), m6A (AUC = 0.817) and m1A (AUC = 0.769). It revealed distinct modification patterns compared with linear RNAs, highlighting RNA-type-specific regulations. We also identified the key features of circRNA-specific modifications, such as the enrichment near the back-splice junctions. Cross-cell line analyses further demonstrated conserved and cell-type-specific modification patterns. Together, these findings reveal, at the computational level, a unique epitranscriptomic landscape associated with circRNAs and establish CircRM as a powerful tool for advancing the study of RNA modifications in circular RNA biology. CircRM is free accessible at: https://github.com/jiayiAnnie17/CircRM.

Related Organizations
Keywords

Nanopore Sequencing, Sequence Analysis, RNA, Problem Solving Protocol, Humans, Computational Biology, RNA, Circular, RNA Processing, Post-Transcriptional

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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hybrid