ncRNA_cond_spa: Gene-centric conditional analysis of long noncoding RNA...

In xihaoli/STAARpipeline: STAARpipeline for Analyzing Whole-Genome/Whole-Exome Sequencing Data

Gene-centric conditional analysis of long noncoding RNA (ncRNA) category using STAAR procedure for imbalance case-control setting

Description

The ncRNA_cond_spa function takes in chromosome, gene name, the object of opened annotated GDS file, and the object from fitting the null model to analyze the association between an imbalanced case-control phenotype and the exonic and splicing category of an ncRNA gene by using STAAR procedure. For each ncRNA category, the conditional STAAR-B p-value is a p-value from an omnibus test that aggregated conditional Burden(1,25) and Burden(1,1), together with conditional p-values of each test weighted by each annotation using Cauchy method.

Usage

ncRNA_cond_spa(
  chr,
  gene_name,
  genofile,
  obj_nullmodel,
  known_loci,
  rare_maf_cutoff = 0.01,
  rv_num_cutoff = 2,
  rv_num_cutoff_max = 1e+09,
  rv_num_cutoff_max_prefilter = 1e+09,
  QC_label = "annotation/filter",
  variant_type = c("SNV", "Indel", "variant"),
  geno_missing_imputation = c("mean", "minor"),
  Annotation_dir = "annotation/info/FunctionalAnnotation",
  Annotation_name_catalog,
  Use_annotation_weights = c(TRUE, FALSE),
  Annotation_name = NULL,
  SPA_p_filter = FALSE,
  p_filter_cutoff = 0.05,
  silent = FALSE
)

Arguments

chr	chromosome.
gene_name	name of the ncRNA gene to be analyzed using STAAR procedure.
genofile	an object of opened annotated GDS (aGDS) file.
obj_nullmodel	an object from fitting the null model, which is either the output from fit_nullmodel function, or the output from fitNullModel function in the GENESIS package and transformed using the genesis2staar_nullmodel function.
known_loci	the data frame of variants to be adjusted for in conditional analysis and should contain 4 columns in the following order: chromosome (CHR), position (POS), reference allele (REF), and alternative allele (ALT) (default = NULL).
rare_maf_cutoff	the cutoff of maximum minor allele frequency in defining rare variants (default = 0.01).
rv_num_cutoff	the cutoff of minimum number of variants of analyzing a given variant-set (default = 2).
rv_num_cutoff_max	the cutoff of maximum number of variants of analyzing a given variant-set (default = 1e+09).
rv_num_cutoff_max_prefilter	the cutoff of maximum number of variants before extracting the genotype matrix (default = 1e+09).
QC_label	channel name of the QC label in the GDS/aGDS file (default = "annotation/filter").
variant_type	type of variant included in the analysis. Choices include "SNV", "Indel", or "variant" (default = "SNV").
geno_missing_imputation	method of handling missing genotypes. Either "mean" or "minor" (default = "mean").
Annotation_dir	channel name of the annotations in the aGDS file (default = "annotation/info/FunctionalAnnotation").
Annotation_name_catalog	a data frame containing the name and the corresponding channel name in the aGDS file.
Use_annotation_weights	use annotations as weights or not (default = TRUE).
Annotation_name	a vector of annotation names used in STAAR (default = NULL).
SPA_p_filter	logical: are only the variants with a normal approximation based p-value smaller than a pre-specified threshold use the SPA method to recalculate the p-value, only used for imbalanced case-control setting (default = FALSE).
p_filter_cutoff	threshold for the p-value recalculation using the SPA method, only used for imbalanced case-control setting (default = 0.05).
silent	logical: should the report of error messages be suppressed (default = FALSE).

Value

A data frame containing the STAAR p-values (including STAAR-O) corresponding to the exonic and splicing category of the given ncRNA gene.

References

Li, Z., Li, X., et al. (2022). A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies. Nature Methods, 19(12), 1599-1611. (pub)

Li, X., Li, Z., et al. (2020). Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nature Genetics, 52(9), 969-983. (pub)

xihaoli/STAARpipeline documentation built on Feb. 9, 2025, 12:39 a.m.