Genome wide quantification of ADAR A-to-I RNA editing activity

Adenosine to inosine (A-to-I) RNA editing by the ADAR enzymes is a common RNA modification that plays an essential role in the innate immune system, preventing false activation by endogenous dsRNAs. Methods for quantification of ADAR activity are sought after, due to an increasing interest in the role of ADARs in cancer and auto-immune disorders, as well as attempts to harness the ADAR enzymes for RNA engineering. Here we present the Alu Editing Index (AEI), a robust and simple-to-use computational tool devised for this purpose, describe its properties and demonstrate its superiority to current quantification methods of ADAR activity. To demonstrate the effectiveness of this tool, we use the AEI to map global editing across a large dataset of healthy human samples, and identify putative regulators of ADAR as well as previously unknown factors affecting the observed Alu editing levels, which should be taken into account in future comparative studies of ADAR activity. The AEI tool is available at https://github.com/a2iEditing/RNAEditingIndexer