LoDEI: a robust and sensitive tool to detect transcriptome-wide differential A-to-I editing in RNA-seq data

Phillipp Torkler, Marina Sauer, Uwe Schwartz, Selim Corbacioglu, Gunhild Sommer and Tilman Heise ()
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Phillipp Torkler: Deggendorf Institute of Technology
Marina Sauer: University Hospital Regensburg
Uwe Schwartz: University of Regensburg
Selim Corbacioglu: University Hospital Regensburg
Gunhild Sommer: University Hospital Regensburg
Tilman Heise: University Hospital Regensburg

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract RNA editing is a highly conserved process. Adenosine deaminase acting on RNA (ADAR) mediated deamination of adenosine (A-to-I editing) is associated with human disease and immune checkpoint control. Functional implications of A-to-I editing are currently of broad interest to academic and industrial research as underscored by the fast-growing number of clinical studies applying base editors as therapeutic tools. Analyzing the dynamics of A-to-I editing, in a biological or therapeutic context, requires the sensitive detection of differential A-to-I editing, a currently unmet need. We introduce the local differential editing index (LoDEI) to detect differential A-to-I editing in RNA-seq datasets using a sliding-window approach coupled with an empirical q value calculation that detects more A-to-I editing sites at the same false-discovery rate compared to existing methods. LoDEI is validated on known and novel datasets revealing that the oncogene MYCN increases and that a specific small non-coding RNA reduces A-to-I editing.

Date: 2024
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DOI: 10.1038/s41467-024-53298-y

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