BACKGROUND: RNA editing is a co-transcriptional modification that increases the 
molecular diversity, alters secondary structure and protein coding sequences by 
changing the sequence of transcripts. The most common RNA editing modification 
is the single base substitution (A→I) that is catalyzed by the members of the 
Adenosine deaminases that act on RNA (ADAR) family. Typically, editing sites are 
identified as RNA-DNA-differences (RDDs) in a comparison of genome and 
transcriptome data from next-generation sequencing experiments. However, a 
method for robust detection of site-specific editing events from replicate 
RNA-seq data has not been published so far. Even more surprising, 
condition-specific editing events, which would show up as differences in RNA-RNA 
comparisons (RRDs) and depend on particular cellular states, are rarely 
discussed in the literature.
RESULTS: We present JACUSA, a versatile one-stop solution to detect single 
nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing 
samples. The performance of JACUSA has been carefully evaluated and compared to 
other variant callers in an in silico benchmark. JACUSA outperforms other 
algorithms in terms of the F measure, which combines precision and recall, in 
all benchmark scenarios. This performance margin is highest for the RNA-RNA 
comparison scenario. We further validated JACUSA's performance by testing its 
ability to detect A→I events using sequencing data from a human cell culture 
experiment and publicly available RNA-seq data from Drosophila melanogaster 
heads. To this end, we performed whole genome and RNA sequencing of HEK-293 
cells on samples with lowered activity of candidate RNA editing enzymes. JACUSA 
has a higher recall and comparable precision for detecting true editing sites in 
RDD comparisons of HEK-293 data. Intriguingly, JACUSA captures most A→I events 
from RRD comparisons of RNA sequencing data derived from Drosophila and HEK-293 
data sets.
CONCLUSION: Our software JACUSA detects single nucleotide variants by comparing 
data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In 
practice, JACUSA shows higher recall and comparable precision in detecting A→I 
sites from RNA-DNA comparisons, while showing higher precision and recall in 
RNA-RNA comparisons.