Tools to Simulate Phenotype(s) with Epistatic Interaction

Provides functions to simulate single or multiple, independent or correlated phenotype(s) with additive, dominance effects and their interactions. Also includes functions to generate phenotype(s) with specific heritability. Flexible and user-friendly options for simulation.


Bug report git repository for SimPhe

SimPhe is an R package dedicated to simulate multiple phenotyes based on genotyping data. The main feature of this package is the possibility to take genetic epistatic effects, not only additive-additive interaction but also additive-dominance and dominance-dominance, heritability and multiple phenotypes into account. Moreover, we provide a variety of convenient functions, including suggestion for set the variation of random variable according to user specified genetic effects and flexible support for input formats, as well as output formats. It also supports the input of plink formats.

Installation

install.packages(SimPhe)

Sample implementation

# load package
library(SimPhe)

First, we show how easy to get phenotype(s) by using sim.phe. Before running sim.phe, we need specify the parameter file and genotype file for simulation. After installing SimPhe, these two toy files exist in package folder. To get the path, type

# get file path of simulation parameters
# (two shared SNP pairs and one independent SNP pair for each phenotype)
fpar.path <- system.file("extdata", "simupars.txt", package="SimPhe")
 
# get file path of genotype file: rows are individuals and columns are SNPs
fgeno.path <- system.file("extdata", "10SNP.txt", package="SimPhe")

Then simulate the phenotypes as designed in the parameter file after loading package:

# simulate phenotype(s)
phe <- sim.phe(sim.pars = fpar.path,
               fgeno = fgeno.path,
               ftype = "snp.head",
               seed = 123,
               fwrite = FALSE)

In the parameter file, we conduct two phenotypes contrbituted by two common SNP pairs with epistatic effects and one independent SNP pair with epistatic effects, the example of simulation parameters, same as the example file, is also included in SimPhe. Users could touch it by typing genepars.

genepars

Phenotype 1 has been set with certain heritability but phenotype 2 has not. We will show whether the heritability of the simulated phenotype 1 is same as the set. SimPhe includes the coefficients and the allele frequencies for simulating phenotype 1: gene.coef and allele.freq, which is extracted from the simulation parameters.

# regression coefficients for simulating phenotype 1
gene.coefficients
# allele frequencies of SNPs for simulating phenotype 1
allele.freq
 
# calculate genetic variance
genevar <- calc.gene.var(gene.coefficients, allele.freq)
 
# the variance of simulated phenotype 1
phe1var <- var(phe[, "p1"])
 
# heritability of simulated phenotype 1
simuht <- genevar / phe1var
simuht

The result is not the exactly 0.6 due to the (pseudo)random numbers generated in R. To get phenotype 2 with a specific heritability, for example, 0.45, we could proceed as:

# get regression coefficients settings for phenotype 2
genecoef <- get.gene.coef(main.pars = specify.pars(genetic.pars = genepars,
                                                   effect.type  = "main",
                                                   phe.index    = 2),
                          epi.pars  = specify.pars(genetic.pars = genepars,
                                                   effect.type  = "epistasis",
                                                   phe.index    = 2))
# get genotype data
genotype <- read.geno(fname = fgeno.path, ftype = "snp.head")
 
# get allele frequencies of the SNPs set for phenotype 2
freq2 <- get.freq(geno = genotype,
                  epi.pars  = specify.pars(genetic.pars = genepars,
                                           effect.type  = "epistasis",
                                           phe.index    = 2))
 
# get noise variation
exp.noise.var <- get.noise.var(gene.coef = genecoef,
                               freq = freq2,
                               heritability = 0.45)

Then when simulating a phenotype, just give this value as argument noise.var to function sim.phe. It will generate a phenotype which has a heritability close to 0.45.

As we mentioned earlier in this article, buiding the correlation by setting the shared interactive SNP pairs cannot be controlled. We can take a look at the correlation between the simulated phenotype 1 and phenotype 2:

# correlation test
cor.test(phe[, "p1"], phe[, "p2"])

According to the result of correlation test, the two simulated phenotypes are significantly correlated but the correlation coefficient is small and the amount cannot easily be predicted. To get a certain amount or higher correlation, we can conduct correlation by applying the correlation matrix to two independent variables. For two phenotypes, if we set different SNP pairs for each, we assume these two phenotypes are independent. Here we give another parameter file to but same genotype file to the arguments in sim.phe, fgenetic.pars and fgeno:

# get file path of simulation parameters
# (different SNP pairs for each phenotype)
fpar.path <- system.file("extdata", "sep_simupars.txt", package="SimPhe")
 
# simulate phenotype(s)
indphe <- sim.phe(sim.pars = fpar.path,
                  fgeno = fgeno.path,
                  ftype = "snp.head",
                  seed = 123,
                  fwrite = FALSE)

We can test the correlation between initial phenotypes with seperated SNP pairs settings:

# test original correlation
cor.test(indphe[, "p1"], indphe[, "p2"])

Apparently, these two phenotypes are not related. We could continue our work on coverting them to be correlated. First, conduct a correlation matrix:

# correlation matrix
corm <- matrix(c(1, 0.6, 0.6, 1), ncol = 2)
corm

Before applying correlation matrix to simulated phenotypes, we would like to know what the data looks like:

apply(indphe, 2, mean)
apply(indphe, 2, sd)

Then we can build correlation between the two initial phenotypes:

# build correlation
corphe <- build.cor.phe(indphe, corMtr = corm)

Now let's test the correlation between the two new phenotypes and see if there is anything difference:

# check mean and standard deviation of new data set
apply(corphe, 2, mean)
apply(corphe, 2, sd)
# test correlation
cor.test(corphe[, "p1"], corphe[, "p2"])

Obviously, there is no significant difference on means and standard deviations between the initial phenotypes and the new phenotypes.

References


  • id: cockerham1977quadratic title: Quadratic analyses of reciprocal crosses author:
    • family: Cockerham given: C. Clark
    • family: Weir given: Bruce Spencer container-title: Biometrics volume: 33 URL: 'http://www.jstor.org/stable/2529312' DOI: 10.2307/2529312 issue: 1 publisher: JSTOR page: 187-203 type: article-journal issued: year: 1977 month: 3
  • id: kao2002modeling title: Modeling epistasis of quantitative trait loci using Cockerham's model author:
    • family: Kao given: Chen-Hung
    • family: Zeng given: Zhao-Bang container-title: Genetics volume: 160 URL: 'http://www.genetics.org/content/160/3/1243' DOI: 10.1534/genetics.104.035857 issue: 3 publisher: Genetics Society of America page: 1243-1261 type: article-journal issued: year: 2002 month: 3 nocite: | @cockerham1977quadratic, @kao2002modeling

News

Reference manual

It appears you don't have a PDF plugin for this browser. You can click here to download the reference manual.

install.packages("SimPhe")

0.2.0 by Beibei Jiang, 8 months ago


https://github.com/beibeiJ/SimPhe


Report a bug at https://github.com/beibeiJ/SimPhe/issues/new


Browse source code at https://github.com/cran/SimPhe


Authors: Beibei Jiang <[email protected]> and Benno Pütz


Documentation:   PDF Manual  


GPL (>= 2) license


Suggests testthat, knitr, rmarkdown


See at CRAN