How To Perform A Pathway Or Network Level Analysis Of Rare Variants?

Question

[ewre]

Hi, all.

I have 10 case exome seq data and many control exome seq data. using GATK, I have got the rare variants related to each sample.

I want to find if there exists anything specific to the rare variants of cases compared with those of controls. apart from check functions of these variants and their known relationship with diseases one by one and sample by sample, are there any approaches which examines these variants in pathway level or network level or systematic level?

What we are keen to find out is that are there any trends or features(genes, gene function, gene network topology, functional pathways etc) specifically related to cases.

Association studies are not proper for me because the number of case samples included in my project is small while the number of spots under study is too big, so the statistical power would be really weak if I do so. this is the main reason which drive me to the systematic analysis of these variants-we want to scale down the number of features involved in our study(single spot -> gene level-> pathway level -> functional group level -> network level).

Any suggestions or discussion would be appreciated.

Answer 1

[JC]

Many variant analysis tools such as Annovar (http://www.openbioinformatics.org/annovar/) includes modular filters, you can compare your data sets in the gene level, biological impact and population frequency, but the features that you want are more integrated in the commercial Ingenuity VA platform (http://www.ingenuity.com/products/variant-analysis).