Performance of various read aligners on simulated data sets with different splice events. For simulated 454 reads (400 bp), segemehl performed significantly better in detecting conventional and ‘non-conventional’ (strand-reversing, long-range) splice junctions. segemehl was the only tool that consistently recalled more than 90% of conventional splice junctions. For ‘non-conventional’ splice events, segemehl extended its lead to 40% for recall without losing precision. Likewise, compared to three of the seven alternative tools, segemehl had a 30% increase in recall for irregularly spliced Illumina reads (100 bp). Compared to TopHat2, it had a slight increase while reporting significantly fewer false positives. At the same time, segemehl’s performance with simulated, regularly spliced Illumina reads was comparable with the other seven tools tested. gs, GSNAP; ms, MapSplice; ru, RUM; se, segemehl; sm, SpliceMap; so, SOAPsplice; st, STAR; to, TopHat2.