Haplotype discovery - 454 data

[Raj]

Hi,
I hope you can help.
I've been asked to search for novel haplotypes from a series of 454 sequenced amplicons.

I would like to know if there is any software that can search for potential haplotypes automatically, to at least provide a short list, to search through.

From my understanding of the AVA software this is fairly manual process to go through detected variants and assess their significance. I've come across similar Haplotype assessment papers, but nothing yet, on actually short listing them.

Many thanks in advance!

[empyrean]

i am working on similar problem. did you find any useful software which does this job??

[JackieBadger]

So you have some idea of what would be "new", i.e. you have a set of original sequences for comparison?
You can uses Sesame (http://www.ncbi.nlm.nih.gov/pubmed/21084284) which sorts your amplicons and BLASTs them against some reference amplicons. However this program can be a real pain to install and run.
jMHC (http://code.google.com/p/jmhc/) I find is much more useful. It will quantify all of your variants within each amplicon and across the data set and give you txt report and table which you can easily sort in Excel. This program runs orders of magnitudes faster on Macs than PCs for some reason.

A word of warning, depending on your study focus/design there are a bunch of confounding factors you need to take into consideration when validating amplicon variants, notably bp-mismatch errors and PCR chimeras. Sadly its not as easy as saying "this is different so its a new variant"...