L-GIREMI uncovers RNA editing sites in long-read RNA-seq

Zhiheng Liu; Giovanni Quinones-Valdez; Ting Fu; Elaine Huang; Mudra Choudhury; Fairlie Reese; Ali Mortazavi; Xinshu Xiao

doi:10.1186/s13059-023-03012-w

L-GIREMI uncovers RNA editing sites in long-read RNA-seq

Genome Biol. 2023 Jul 20;24(1):171. doi: 10.1186/s13059-023-03012-w.

Authors

Zhiheng Liu¹, Giovanni Quinones-Valdez¹, Ting Fu², Elaine Huang³, Mudra Choudhury³, Fairlie Reese^{4

5}, Ali Mortazavi^{4

5}, Xinshu Xiao^{6

7

8}

Affiliations

¹ Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
² Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, CA, USA.
³ Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA.
⁴ Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
⁵ Center for Complex Biological Systems, University of California, Irvine, CA, USA.
⁶ Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA. gxxiao@ucla.edu.
⁷ Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, CA, USA. gxxiao@ucla.edu.
⁸ Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA. gxxiao@ucla.edu.

Abstract

Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases. Applied to PacBio RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. Additionally, our analysis uncovered novel insights about RNA editing occurrences in single molecules and double-stranded RNA structures. L-GIREMI provides a valuable means to study nucleotide variants in long-read RNA-seq.

Keywords: A-to-I editing; Double-stranded RNA; Mutual information.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

High-Throughput Nucleotide Sequencing / methods
Nucleotides
RNA Editing*
RNA-Seq
Sequence Analysis, RNA / methods
Transcriptome*

Substances

Nucleotides

Abstract

Publication types

MeSH terms

Substances

Grants and funding