Hope this doesn't raise more questions than answering yours, and this is just my personal experience. I must say, Blat gave me quite a good impression in the past. It has support for large inserts, controlled via
fine parameters. I am not aware of another tool that gives you control over that so easily. And it also seems to be able to align more reads to my reference than many of the dedicated short-read tools, and no need to build an store an index. What's not so good: e.g. no SAM/CIGAR output format, not multithreaded, the licence, etc. And it can be beaten in sensitivity and speed.
I made a little comparison, took a random sample (maybe some 10.000 for speed) of my reads in fastq and fasta and simply try how many reads can be mapped with different aligners, caveat: didn't care for alignment quality (should check for validity though), and no Introns, and maybe it's totally screwed, here is my list, your mileage may vary:
- BFAST (~85%) (BLAT-like fast accurate search tool)
- LastZ (~80%)
- Novoalign (~80%)
- Blat (~74%)
- Bowtie (~60%)
- bwa (~54%)
I recommend: Bowtie&Tophat: because it is developed specifically for that, LastZ: has hell of a lot parameters, SAM output etc., BFAST: because it gave me most alignments, was the slowest though.
You have to find out, how to set parameters to allow for large inserts/introns though, try to play with the gap costs. Would be very nice if you post your experiences!