sqtl.seeker: sQTL seeker
In jmonlong/sQTLseekeR: Splicing QTL discovery tool

Description Usage Arguments Details Value Author(s)

sqtl.seeker is the main function of sQTLseekeR package. From transcript relative expression, prepared using prepare.trans.exp, information about the gene location and the path to an ordered genotype file, indexed by function index.genotype, association between each SNP and the transcript relative expression is tested. Eventually, svQTL, i.e. SNPs affecting splicing variability can also be tested to pinpoint potential false sQTL (see Details).

sqtl.seeker(tre.df, genotype.f, gene.loc, genic.window = 5000,
  min.nb.ext.scores = 1000, nb.perm.max = 1e+06,
  nb.perm.max.svQTL = 10000, svQTL = FALSE, approx = TRUE,
  verbose = TRUE)

`tre.df`	a data.frame with transcript relative expression produced by 'prepare.trans.exp'.
`genotype.f`	the name of the genotype file. This file need to be ordered by position, compressed and indexed using 'index.genotype' or externally using tabix (samtools). Must have column 'snpId'.
`gene.loc`	a data.frame with the genes location. Columns 'chr', 'start', 'end' and 'geneId' are required.
`genic.window`	the window(bp) around the gene in which the SNPs are tested. Default is 5000 (i.e. 5kb).
`min.nb.ext.scores`	the minimum number of permuted score higher than the highest true score to allow the computation to stop. Default is 1000.
`nb.perm.max`	the maximum number of permutations. Default is 1e6.
`nb.perm.max.svQTL`	the maximum number of permutations for the svQTL computation. Default is 1e4.
`svQTL`	should svQTLs test be performed in addition to sQTLs. Default is FALSE. Warning: computation of svQTLs cannot rely on asymptotic approximation, hence the heavy permutations will considerably increase the running time.
`approx`	should the asymptotic distribution be used instead of permutations. Default is TRUE.
`verbose`	Should the gene IDs be outputed when analyzed. Default is TRUE. Mainly for debugging.

A set of filters is automatically used to remove SNPs which are unpractical or not informative. Precisely, these filters remove SNP with :

more than 3 unknown genotypes
less than 5 samples in any genotype group
less than 5 different splicing pattern (needed for permutation efficiency) in any genotype group

Testing difference in transcript relative expression between genotype groups assumes homogeneity of the variances in these groups. Testing this assumption is more complex and computationnally intensive but if needed the user can choose to test for svQTL (splicing variability QTL), i.e. gene/SNPs where this assumption is violated, by using the svQTL=TRUE. This test is run in parallel to the sQTL tests, but the computation time will be considerably higher. For this reason, another parameter can be tweaked, nb.perm.max.svQTL, to reduce the number of permutation for the svQTL tests if needed for feasibility reasons.

The permutation process is optimized by computing one permuted distribution per gene and using a number of permutation depending on how extreme the true scores are compared to the permuted ones. To decrease even more the computation time, an approximation of the null F distribution was given by Anderson & Robinson (2003), as a misture of Chi-square distributions whoose parameters are derived from the eigen values of the distance matrix.

In addition to the F score and P-value, the maximum difference(MD) in relative expression between genotype groups is reported. This is to be used as a measure of the size of the effect. For example, if 'md' is 0.2 there is one transcript whose relative expression shifted by 20

a data.frame with columns

`geneId`	the gene name
`snpId`	the SNP name
`F`	the F score
`nb.groups`	the number of genotype groups (2 or 3)
`md`	the maximum difference in relative expression between genotype groups (see Details)
`tr.first/tr.second`	the transcript IDs of the two transcripts that change the most (and symetrically).
`pv`	the P-value
`nb.perms`	the number of permutation used for the P-value computation
`F.svQTL/pv.svQTL/nb.perms.svQTL`	idem for svQTLs, if 'svQTL=TRUE'.