I need to precisely align NGS data. The problem is, in global alignment I loose plenty of reads (20%), while local alignment fails to align merely 5% of reads. I don't care that much about 3'-end, but 5'-end has to be aligned with 1bp precision. Iterative hard-clipping of 3'-ends helps, but it would be perfect to do it in one run. Do you know of any program that can precisely align 5'-end and allows for soft-clipping of 3'-end at the same time?
I don't know an optimal solution for this, once I had a similar case where some reads need trimming with different sizes, I use Blat to align to the reference and then use some Perl scripts to convert the PSLX to a valid SAM format, inserting soft-masking ends and indels flags in the CIGAR when it was required. The mapping worked terrific but it was extremely slow. Do you want to take a look? http://github.com/caballero/RNAseq-Pi/ the files megablat.pl and pslx2sam.pl under bin/