Identifying de novo variants in trio data

[vivek_]

I have trio datasets that I have phased using GATK's PhaseByTransmission and ReadbackedPhasing walkers.

My target is to identify de novo mutations from this data.

I'm creating a candidate de novo mutations dataset by checking for variants that are present in the offspring and not in either of the parents as well as looking for variant sites where there are mendelian violations.

I'd like to know how to proceed in filtering through this dataset to confidently ascertain variants that are de novo from the rest.

I'd appreciate any inputs/ideas on creating a methodology to go about this analysis.

[rosa_dentellare]

Hi Vivek,

did u managed to find a way to proceed with the analysis?

[vivek_]

I ended up creating a method using genotype quality scores and allele fractions form the GATK VCFs to identify candidate denovo mutations.

[rosa_dentellare]

Would you care to elaborate more Vivek? as I myself am also interested in looking at those accumulative and de novo variants.

[trackavinash]

Hi,
This is definitely a plug but I'd encourage you to check out our tool Denovogear which is designed to detect denovo mutations in trios using a Bayesian model that lets you set mutation rate priors and filter denovo calls based on posterior probabilities,

https://sourceforge.net/p/denovogear/home/Home/

Cheers,
Avinash

[rosa_dentellare]

Thanks...will check d tool out =)

[vivek_]

I'd recommend Denovogear as well and I used it as part of my analysis.

This publication was very helpful for me in formulating my other analysis methods:

http://www.nature.com/nature/journal/v488/n7412/full/nature11396.html

Some of the cut-offs and filters etc can be modified based on your read coverage.

[rosa_dentellare]

Thanks Vivek, appreciate it. Also, do you happen to have a copy for the paper?..I do not have access to Nature. Would appreciate that so much