qtl_clumpR: Clump QTL SNPs based on gene

In Sabor117/PathWAS: Creates predictive models of biological pathway functionality

Clump QTL SNPs based on gene

Description

qtl_clumpR returns two outputs: a compiled data frame of SNPs for a given pathway along with selected clumped SNPs

Usage

qtl_clumpR(
  end_point,
  path_select,
  path_gene_list,
  biomart_map,
  all_snps,
  all_snps_genecol = "gene_ensembl",
  qtl_gene_identifier = "ensembl_gene_id",
  bfile,
  plink_bin,
  MAF_filter = NA,
  MAF_col = "MAF",
  def_tmpDir = tempdir()
)

Arguments

end_point	character. Name of gene in HGNC format (or equivalent). Required for excluding the gene from the list of QTLs used.
path_select	character. Name of pathway. Format is unimportant, only used for aesthetics purposes.
path_gene_list	list. The output of either smple_paths or genepath_ListR. A list of Entrez IDs of all genes in your pathway.
biomart_map	data frame. Data frame of gene names including at least entrezgene_id, external_gene_name and whatever format of gene name is used in the QTLs (e.g. Ensembl ID).
all_snps	data frame. All SNPs for QTLs to be filtered in analysis. May be significant QTLs only.
all_snps_genecol	character or numeric. Name of the column containing the gene name from the QTLs in all_snps. Default is "gene_ensembl" as many QTL datasets tend to use Ensembl IDs of some description. Can also be the number of the column containing the gene names.
qtl_gene_identifier	character or numeric. Equivalent naming format from the SNPs in the BioMart map. E.g. if the QTLs use UniProt or Ensembl IDs, then this should be the equivalent from BioMart.
bfile	character. Location of the Plink files of your reference genotype.
plink_bin	character. Location of the local version of the plink executable.
MAF_filter	logical. Define if you want to filter your clumped SNPs by MAF.
MAF_col	character. Column name or number for the data frame which contains the MAF for filtering SNPs.
def_tmpDir	character. Local directory for saving temporary files for clumping - may prevent some crashes.

Details

This function takes as an input several large data frames. You must input a data frame of your QTLs (e.g. qQTLs/pQTLs) and also a list of your genes for your pathway. This can optionally be filtered to only include significant QTLs/eGenes (and we recommemnd this).

The QTLs must (for this function) at minimum include 4 columns: rsid column - e.g. rs1234. snpid column - a unique identifier for every SNP. We suggest the format "chromosome:position_a1_a2" but this is not compulsory. p - the QTL p-value for each SNP. gene - each SNP must be labeled according to which gene it is a QTL for. Many eQTL data sets use Ensembl IDs as a default. The name of this column can be chosen as a variable of the function.

SNPs should be included for every gene available in the pathway. Where SNPs overlap between genes, this function will select said SNP only once based on the lowest QTL p-value.

You must also include a BioMart file (from https://www.ensembl.org/biomart/martview/ or using package biomaRt) in order to convert the gene names between the names used in the QTLs and Entrez (KEGG) gene IDs.

The clumping is performed using the package ieugwasr (https://rdrr.io/github/MRCIEU/ieugwasr/). This requires access to a locally installed version of plink and access to a reference genotype in plink format (I.e. bed/bim/fam).

For the requirement of a reference genotype you should input the location of the files + the prefix of your plink files (e.g. if you have /opt/data/reference/cohort_new_allchr.bed, /opt/data/reference/cohort_new_allchr.bim, cohort_new_allchr.fam use bfile = "/opt/data/reference/cohort_new_allchr"). If your plink files are divided by chromosome (e.g. cohort_new_chr1.bed : cohort_new_chr2.bed) then input the prefix with " chromosome number: bfile = "/opt/data/reference/cohort_new_chr

This function will output (as a list) two things: the filtered data frame of all the QTL SNPs for the pathway and a data frame of the clumped SNPs (usually only a few per locus).

Sabor117/PathWAS documentation built on Nov. 29, 2024, 7:44 a.m.