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more difficult to map and the implementation could
still be improvedto obtain higher overall performance
and a lower memory footprint.
Within a candidate region, a gapped alignment is
first build using a chain of the seeds found within
this region. The greedy chaining algorithm is cur-
rently the major source of miss-alignments and could
be replaced by an optimal collinear chaining algo-
rithm (Abouelhoda, 2007). Other causes of misalign-
ments include failure to detect splice sites at the ends
of reads and failure to differentiate two consecutive
introns separated by an exon smaller than the mini-
mum seed length.
The run time could be further decreased by select-
ing good settings for parameters, such as minimum
seed length, but also by, for example, using a bit-
parallel dynamic programming implementation in the
extension stage. The memory footprint of the index
could further be reduced by bit-encoding the refer-
ence sequence.
In addition to algorithmic improvements, more
rigorous tests need to be performed on large and var-
ied data sets and experimental results need to be com-
pared to a larger set of spliced aligners, using different
parameter settings.
Finally, the current implementation of mesalina
still lacks some of the features other spliced align-
ers support, including specific algorithms for the de-
tection of micro-exons and alternative splicing, and
paired-end read mapping. We also acknowledge the
need for clear and intuitive command line options and
good portability of the tool.
ACKNOWLEDGEMENTS
The work of MV is supported by the Agency for In-
novation by Science and Technology of the Flemish
government [contract SB-101609]. All authors ac-
knowledge the support of Ghent University: MRP
Bioinformatics: from nucleotides to networks (N2N).
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