ksburden

Most commonly used rare variant tests do not take the position of individual variants into account when testing a gene or a genomic region. The ksburden test aims to make use of hypothesized differences in the distribution of rare variants between cases and controls.

Prerequisites

Currently ksburden only runs on Linux machine machines. No particular requirements are needed prior installation with the exception of cmake.

Installing

Installation is simple. Just clone this repository then run:

cmake .
make

The necessary libraries are then downloaded and the program is compiled.

Usage

Gene Based Testing

After compilation the program ksburden can be found in the bin directory. It is fairly simple and requires only three inputs as shown below

Flag	Function
--genotypes	variant file in vcf format
--variant	list of variants in tab format
--ped	pedigree file in plink format

The variant file is a tab separated text file with 3 columns:

1. Chromosome
2. Position
3. Gene name

In addition a number of other options can be specified.

Flag	Function
--out	output file name
--iter	number of iterations
--ks	perform the KS test in addition to ksburden
--burden	perform the burden test in addition to ksburden
--CMC	perform the CMC test in addition to ksburden

Simulations

In addition to the ksburden test I also included a simulation framework. The framework simulates different mutation scenarios and estimates statistical power for various tests.

For example the code below takes a vcf file skat.matrix.vcf and simulates 100 times a case-control sample with a life-time disease risk of 10%. It then estimates statistical power for ksburden, burden and cmc. A full description of all flags can be found below.

simmat="skat.matrix.vcf"

sim --simmat=$simmat \
	--lifetimerisk=0.10 \
	--powerIter=10 \
	--iter=100 \
	--threads=5 \
	--tests="ksburden,burden,cmc" \
	--minEffect=0.010 \
	--maxEffect=0.010 \
	--effectSteps=0.001 \
	--percentageSteps=0.1 \
	--maxPercentage=1.0 \
	--verbose=9 \
	--path="path/to/somulation/folder/" \
	--out="sometest.txt" 

Required Flags:

Flag	Function
--genotypes	variant file in vcf or plink format (see --simmat)
--variant	list of variants in tab format
--gene	name of gene to do simulation on
--simmat	'vcf' or 'plink' for files in the corresponding format

Optional flags:

Flag	Function
--threads	number of threads to use
--subjects	total number of subjects
--powerIter	number of iteration to calculate power
--verbose	verbose level
--iter	number of iterations
--lifetimerisk	life time risk
--tests	models to perform, should be a string separated by commas
--minEffect	minimal effect size
--maxEffect	maximal effect size
--effectSteps	effect size steps
--percentageSteps	percentage of causal variants steps in percentage
--maxPercentage	maximal percent of gene covered by causal variants
--causalVar	number of causal mutations
--outPath	output path of the simulations

Built With

• Armadillo - C++ linear algebra library
• OpenMP - Shared Memory multiprocessing programming library
• Easylogging++ - C++ logging library
• LibStatGen - C++ library for statistical genetics

Authors

• Robert Milan Porsch

License

This project is licensed under the MIT License - see the LICENSE.md file for details