R/Gene_Centric_Coding_Results_Summary.R
In xihaoli/STAARpipelineSummary: Summarization and Visualization of Analysis Results Generated by STAARpipeline
Defines functions
Gene_Centric_Coding_Results_Summary
Documented in
Gene_Centric_Coding_Results_Summary
#' Summarize gene-centric coding analysis results generated by \code{STAARpipeline} package and
#' perform conditional analysis for (unconditionally) significant coding masks by adjusting for a given list of known variants
#'
#' The \code{Gene_Centric_Coding_Results_Summary} function takes in the objects of gene-centric coding analysis results
#' generated by \code{STAARpipeline} package,
#' the object from fitting the null model, and the set of known variants to be adjusted for in conditional analysis
#' to summarize the gene-centric coding analysis results and analyze the conditional association between a quantitative/dichotomous phenotype
#' (including imbalanced case-control design) and
#' the rare variants in the unconditional significant coding masks.
#' @param agds_dir file directory of annotated GDS (aGDS) files for all chromosomes (1-22)
#' @param gene_centric_coding_jobs_num the number of gene-centric coding analysis results generated by \code{STAARpipeline} package.
#' @param input_path the directory of gene-centric coding analysis results that generated by \code{STAARpipeline} package.
#' @param output_path the directory for the output files.
#' @param gene_centric_results_name file name of gene-centric coding analysis results generated by \code{STAARpipeline} package.
#' @param obj_nullmodel an object from fitting the null model, which is either the output from \code{fit_nullmodel} function in the \code{STAARpipeline} package,
#' or the output from \code{fitNullModel} function in the \code{GENESIS} package and transformed using the \code{genesis2staar_nullmodel} function in the \code{STAARpipeline} package.
#' @param 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).
#' @param cMAC_cutoff the cutoff of the minimum number of the cumulative minor allele of variants in the masks
#' when summarizing the results (default = 0).
#' @param method_cond a character value indicating the method for conditional analysis.
#' \code{optimal} refers to regressing residuals from the null model on \code{known_loci}
#' as well as all covariates used in fitting the null model (fully adjusted) and taking the residuals;
#' \code{naive} refers to regressing residuals from the null model on \code{known_loci}
#' and taking the residuals (default = \code{optimal}).
#' @param rare_maf_cutoff the cutoff of maximum minor allele frequency in
#' defining rare variants (default = 0.01).
#' @param QC_label channel name of the QC label in the GDS/aGDS file (default = "annotation/filter").
#' @param variant_type type of variant included in the analysis. Choices include "SNV", "Indel", or "variant" (default = "SNV").
#' @param geno_missing_imputation method of handling missing genotypes. Either "mean" or "minor" (default = "mean").
#' @param Annotation_dir channel name of the annotations in the aGDS file \cr (default = "annotation/info/FunctionalAnnotation").
#' @param Annotation_name_catalog a data frame containing the name and the corresponding channel name in the aGDS file.
#' @param Use_annotation_weights use annotations as weights or not (default = FALSE).
#' @param Annotation_name a vector of annotation names used in STAAR (default = NULL).
#' @param alpha p-value threshold of significant results (default = 2.5E-06).
#' @param manhattan_plot output manhattan plot or not (default = FALSE).
#' @param QQ_plot output Q-Q plot or not (default = FALSE).
#' @param cond_null_model_name the null model name for conditional analysis in the SPA setting, only used for imbalanced case-control setting (default = NULL).
#' @param cond_null_model_dir the directory of storing the null model for conditional analysis in the SPA setting, only used for imbalanced case-control setting (default = NULL).
#' @param 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).
#' @param p_filter_cutoff threshold for the p-value recalculation using the SPA method, only used for imbalanced case-control setting (default = 0.05).
#' @return The function returns the following analysis results:
#' @return \code{coding_sig.csv}: a matrix that summarizes the unconditional significant coding masks detected by STAAR-O or STAAR-B in imbalanced case-control setting (STAAR-O/-B pvalue smaller than the threshold alpha),
#' including gene name ("Gene name"), chromosome ("chr"), coding functional category ("Category"), number of variants ("#SNV"),
#' and unconditional p-values of set-based tests SKAT ("SKAT(1,25)"), Burden ("Burden(1,1)"), ACAT-V ("ACAT-V(1,25)") and STAAR-O ("STAAR-O")
#' or unconditional p-values of set-based tests Burden ("Burden(1,1)") and STAAR-B ("STAAR-B") for imbalanced case-control setting.
#' @return \code{coding_sig_cond.csv}: a matrix that summarized the conditional analysis results of unconditional significant coding masks detected by STAAR-O or STAAR-B in imbalanced case-control setting (available if known_loci is not a NULL),
#' including gene name ("Gene name"), chromosome ("chr"), coding functional category ("Category"), number of variants ("#SNV"),
#' and conditional p-values of set-based tests SKAT ("SKAT(1,25)"), Burden ("Burden(1,1)"), ACAT-V ("ACAT-V(1,25)") and STAAR-O ("STAAR-O")
#' or conditional p-values of set-based tests Burden ("Burden(1,1)") and STAAR-B ("STAAR-B") for imbalanced case-control setting.
#' @return \code{results_plof_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the putative loss of function variants (plof) for all protein-coding genes across the genome.
#' @return \code{plof_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof masks.
#' @return \code{plof_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof masks (available if known_loci is not a NULL).
#' @return \code{results_plof_ds_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the putative loss of function variants and disruptive missense variants (plof_ds) for all protein-coding genes across the genome.
#' @return \code{plof_ds_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof_ds masks.
#' @return \code{plof_ds_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof_ds masks (available if known_loci is not a NULL).
#' @return \code{results_disruptive_missense_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the disruptive missense variants (disruptive_missense) for all protein-coding genes across the genome.
#' @return \code{disruptive_missense_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant disruptive_missense masks.
#' @return \code{disruptive_missense_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant disruptive_missense masks (available if known_loci is not a NULL).
#' @return \code{results_missense_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the missense variants (missense) for all protein-coding genes across the genome.
#' @return \code{missense_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant missense masks.
#' @return \code{missense_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant missense masks (available if known_loci is not a NULL).
#' @return \code{results_synonymous_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the synonymous variants (synonymous) for all protein-coding genes across the genome.
#' @return \code{synonymous_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant synonymous masks.
#' @return \code{synonymous_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant synonymous masks (available if known_loci is not a NULL).
#' @return manhattan plot (optional) and Q-Q plot (optional) of the gene-centric coding analysis results.
#' @references Li, Z., Li, X., et al. (2022). A framework for detecting
#' noncoding rare-variant associations of large-scale whole-genome sequencing
#' studies. \emph{Nature Methods}, \emph{19}(12), 1599-1611.
#' (\href{https://doi.org/10.1038/s41592-022-01640-x}{pub})
#' @export
Gene_Centric_Coding_Results_Summary <- function(agds_dir,gene_centric_coding_jobs_num,input_path,output_path,gene_centric_results_name,
obj_nullmodel,known_loci=NULL,cMAC_cutoff=0,
method_cond=c("optimal","naive"),rare_maf_cutoff=0.01,
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=FALSE,Annotation_name=NULL,
alpha=2.5E-06,manhattan_plot=FALSE,QQ_plot=FALSE,
cond_null_model_name=NULL,cond_null_model_dir=NULL,
SPA_p_filter=FALSE,p_filter_cutoff=0.05){
## evaluate choices
method_cond <- match.arg(method_cond)
variant_type <- match.arg(variant_type)
geno_missing_imputation <- match.arg(geno_missing_imputation)
## SPA status
if(!is.null(obj_nullmodel$use_SPA))
{
use_SPA <- obj_nullmodel$use_SPA
}else
{
use_SPA <- FALSE
}
#######################################################
# summarize unconditional analysis results
#######################################################
results_coding_genome <- c()
for(kk in 1:gene_centric_coding_jobs_num)
{
print(kk)
results_coding <- get(load(paste0(input_path,gene_centric_results_name,"_",kk,".Rdata")))
results_coding_genome <- c(results_coding_genome,results_coding)
}
results_plof_genome <- c()
results_plof_ds_genome <- c()
results_missense_genome <- c()
results_disruptive_missense_genome <- c()
results_synonymous_genome <- c()
for(kk in 1:length(results_coding_genome))
{
results <- results_coding_genome[[kk]]
if(is.null(results)==FALSE)
{
### plof
if(results[3]=="plof")
{
results_plof_genome <- rbind(results_plof_genome,results)
}
### plof_ds
if(results[3]=="plof_ds")
{
results_plof_ds_genome <- rbind(results_plof_ds_genome,results)
}
### missense
if(results[3]=="missense")
{
results_missense_genome <- rbind(results_missense_genome,results)
}
### disruptive_missense
if(results[3]=="disruptive_missense")
{
results_disruptive_missense_genome <- rbind(results_disruptive_missense_genome,results)
}
### synonymous
if(results[3]=="synonymous")
{
results_synonymous_genome <- rbind(results_synonymous_genome,results)
}
}
if(kk%%1000==0)
{
print(kk)
}
}
###### cMAC_cutoff
# plof
results_plof_genome <- results_plof_genome[results_plof_genome[,"cMAC"]>cMAC_cutoff,]
# plof + disruptive missense
results_plof_ds_genome <- results_plof_ds_genome[results_plof_ds_genome[,"cMAC"]>cMAC_cutoff,]
# missense
results_missense_genome <- results_missense_genome[results_missense_genome[,"cMAC"]>cMAC_cutoff,]
# disruptive missense
results_disruptive_missense_genome <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"cMAC"]>cMAC_cutoff,]
# synonymous
results_synonymous_genome <- results_synonymous_genome[results_synonymous_genome[,"cMAC"]>cMAC_cutoff,]
### recalculate missense pvalue
if(cMAC_cutoff > 0)
{
genes_name_disruptive_missense <- as.vector(unlist(results_disruptive_missense_genome[,1]))
genes_name_missense <- as.vector(unlist(results_missense_genome[,1]))
recal_id <- (1:dim(results_missense_genome)[1])[(!genes_name_missense%in%genes_name_disruptive_missense)]
for(kk in recal_id)
{
print(kk)
results_m <- results_missense_genome[kk,]
if(use_SPA)
{
## disruptive missense cMAC < cut_off, set p-value to 1
results_missense_genome[kk,"Burden(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"Burden(1,1)-Disruptive"] <- 1
apc_num <- (length(results_m)-10)/2
p_seq <- c(1:apc_num,1:apc_num+(apc_num+1))
## calculate STAAR-B
pvalues_sub <- as.numeric(results_m[6:length(results_m)][p_seq])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B"] <- 1
}
}
results_missense_genome[kk,"STAAR-B"] <- results_m["STAAR-B"]
## calculate STAAR-B(1,25)
pvalues_sub <- as.numeric(results_m[6:length(results_m)][c(1:apc_num)])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B(1,25)"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B(1,25)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,25)"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B(1,25)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,25)"] <- 1
}
}
results_missense_genome[kk,"STAAR-B(1,25)"] <- results_m["STAAR-B(1,25)"]
## calculate STAAR-B(1,1)
pvalues_sub <- as.numeric(results_m[6:length(results_m)][c(1:apc_num+(apc_num+1))])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B(1,1)"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B(1,1)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,1)"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B(1,1)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,1)"] <- 1
}
}
results_missense_genome[kk,"STAAR-B(1,1)"] <- results_m["STAAR-B(1,1)"]
}else
{
## disruptive missense cMAC < cut_off, set p-value to 1
results_missense_genome[kk,"Burden(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"Burden(1,1)-Disruptive"] <- 1
results_missense_genome[kk,"SKAT(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"SKAT(1,1)-Disruptive"] <- 1
results_missense_genome[kk,"ACAT-V(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"ACAT-V(1,1)-Disruptive"] <- 1
apc_num <- (length(results_m)-19)/6
p_seq <- c(1:apc_num,1:apc_num+(apc_num+1),1:apc_num+2*(apc_num+1),1:apc_num+3*(apc_num+1),1:apc_num+4*(apc_num+1),1:apc_num+5*(apc_num+1))
results_m["STAAR-O"] <- CCT(as.numeric(results_m[6:length(results_m)][p_seq]))
results_m["STAAR-S(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num)]))
results_m["STAAR-S(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+(apc_num+1))]))
results_m["STAAR-B(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+2*(apc_num+1))]))
results_m["STAAR-B(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+3*(apc_num+1))]))
results_m["STAAR-A(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+4*(apc_num+1))]))
results_m["STAAR-A(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+5*(apc_num+1))]))
}
}
}
###### whole-genome results
# plof
save(results_plof_genome,file=paste0(output_path,"plof.Rdata"))
# plof + disruptive missense
save(results_plof_ds_genome,file=paste0(output_path,"plof_ds.Rdata"))
# missense
save(results_missense_genome,file=paste0(output_path,"missense.Rdata"))
# disruptive missense
save(results_disruptive_missense_genome,file=paste0(output_path,"disruptive_missense.Rdata"))
# synonymous
save(results_synonymous_genome,file=paste0(output_path,"synonymous.Rdata"))
if(use_SPA)
{
###### significant results
# plof
plof_sig <- results_plof_genome[results_plof_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(plof_sig,file=paste0(output_path,"plof_sig.csv"))
# missense
missense_sig <- results_missense_genome[results_missense_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(missense_sig,file=paste0(output_path,"missense_sig.csv"))
# synonymous
synonymous_sig <- results_synonymous_genome[results_synonymous_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(synonymous_sig,file=paste0(output_path,"synonymous_sig.csv"))
# plof_ds
plof_ds_sig <- results_plof_ds_genome[results_plof_ds_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(plof_ds_sig,file=paste0(output_path,"plof_ds_sig.csv"))
# disruptive_missense
disruptive_missense_sig <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(disruptive_missense_sig,file=paste0(output_path,"disruptive_missense_sig.csv"))
# coding results
coding_sig <- rbind(plof_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")],
missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,synonymous_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,plof_ds_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,disruptive_missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
write.csv(coding_sig,file=paste0(output_path,"coding_sig.csv"))
}else
{
# plof
plof_sig <- results_plof_genome[results_plof_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(plof_sig,file=paste0(output_path,"plof_sig.csv"))
# missense
missense_sig <- results_missense_genome[results_missense_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(missense_sig,file=paste0(output_path,"missense_sig.csv"))
# synonymous
synonymous_sig <- results_synonymous_genome[results_synonymous_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(synonymous_sig,file=paste0(output_path,"synonymous_sig.csv"))
# plof_ds
plof_ds_sig <- results_plof_ds_genome[results_plof_ds_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(plof_ds_sig,file=paste0(output_path,"plof_ds_sig.csv"))
# disruptive_missense
disruptive_missense_sig <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(disruptive_missense_sig,file=paste0(output_path,"disruptive_missense_sig.csv"))
# coding results
coding_sig <- rbind(plof_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")],
missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,synonymous_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,plof_ds_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,disruptive_missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
write.csv(coding_sig,file=paste0(output_path,"coding_sig.csv"))
}
#######################################################
# conditional analysis
#######################################################
if(length(known_loci)!=0)
{
if(!use_SPA)
{
### plof
plof_sig_cond <- c()
if(length(plof_sig)!=0)
{
if((class(plof_sig)[1]!="matrix")&(class(plof_sig)[1]!="data.frame"))
{
plof_sig <- matrix(plof_sig,nrow=1)
}
for(k in 1:dim(plof_sig)[1])
{
chr <- as.numeric(plof_sig[k,2])
gene_name <- as.character(plof_sig[k,1])
category <- as.character(plof_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
plof_sig_cond <- rbind(plof_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(plof_sig_cond,file=paste0(output_path,"plof_sig_cond.csv"))
### missense
missense_sig_cond <- c()
if(length(missense_sig)!=0)
{
if((class(missense_sig)[1]!="matrix")&(class(missense_sig)[1]!="data.frame"))
{
missense_sig <- matrix(missense_sig,nrow=1)
}
for(k in 1:dim(missense_sig)[1])
{
chr <- as.numeric(missense_sig[k,2])
gene_name <- as.character(missense_sig[k,1])
category <- as.character(missense_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
missense_sig_cond <- rbind(missense_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(missense_sig_cond,file=paste0(output_path,"missense_sig_cond.csv"))
### synonymous
synonymous_sig_cond <- c()
if(length(synonymous_sig)!=0)
{
if((class(synonymous_sig)[1]!="matrix")&(class(synonymous_sig)[1]!="data.frame"))
{
synonymous_sig <- matrix(synonymous_sig,nrow=1)
}
for(k in 1:dim(synonymous_sig)[1])
{
chr <- as.numeric(synonymous_sig[k,2])
gene_name <- as.character(synonymous_sig[k,1])
category <- as.character(synonymous_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
synonymous_sig_cond <- rbind(synonymous_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(synonymous_sig_cond,file=paste0(output_path,"synonymous_sig_cond.csv"))
### plof_ds
plof_ds_sig_cond <- c()
if(length(plof_ds_sig)!=0)
{
if((class(plof_ds_sig)[1]!="matrix")&(class(plof_ds_sig)[1]!="data.frame"))
{
plof_ds_sig <- matrix(plof_ds_sig,nrow=1)
}
for(k in 1:dim(plof_ds_sig)[1])
{
chr <- as.numeric(plof_ds_sig[k,2])
gene_name <- as.character(plof_ds_sig[k,1])
category <- as.character(plof_ds_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
plof_ds_sig_cond <- rbind(plof_ds_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(plof_ds_sig_cond,file=paste0(output_path,"plof_ds_sig_cond.csv"))
### disruptive_missense
disruptive_missense_sig_cond <- c()
if(length(disruptive_missense_sig)!=0)
{
if((class(disruptive_missense_sig)[1]!="matrix")&(class(disruptive_missense_sig)[1]!="data.frame"))
{
disruptive_missense_sig <- matrix(disruptive_missense_sig,nrow=1)
}
for(k in 1:dim(disruptive_missense_sig)[1])
{
chr <- as.numeric(disruptive_missense_sig[k,2])
gene_name <- as.character(disruptive_missense_sig[k,1])
category <- as.character(disruptive_missense_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
disruptive_missense_sig_cond <- rbind(disruptive_missense_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(disruptive_missense_sig_cond,file=paste0(output_path,"disruptive_missense_sig_cond.csv"))
## coding cond
coding_sig_cond <- rbind(plof_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")],
missense_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,synonymous_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,plof_ds_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,disruptive_missense_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
write.csv(coding_sig_cond,file=paste0(output_path,"coding_sig_cond.csv"))
}else
{
### synonymous
synonymous_sig_cond <- c()
if(length(synonymous_sig)!=0)
{
if((class(synonymous_sig)[1]!="matrix")&(class(synonymous_sig)[1]!="data.frame"))
{
synonymous_sig <- matrix(synonymous_sig,nrow=1)
}
for(k in 1:dim(synonymous_sig)[1])
{
chr <- as.numeric(synonymous_sig[k,2])
gene_name <- as.character(synonymous_sig[k,1])
category <- as.character(synonymous_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- synonymous_sig[k,,drop=FALSE]
res_cond[1,3] <- "synonymous_cond"
}
synonymous_sig_cond <- rbind(synonymous_sig_cond,res_cond)
}
}
write.csv(synonymous_sig_cond,file=paste0(output_path,"synonymous_sig_cond.csv"))
### plof
plof_sig_cond <- c()
if(length(plof_sig)!=0)
{
if((class(plof_sig)[1]!="matrix")&(class(plof_sig)[1]!="data.frame"))
{
plof_sig <- matrix(plof_sig,nrow=1)
}
for(k in 1:dim(plof_sig)[1])
{
chr <- as.numeric(plof_sig[k,2])
gene_name <- as.character(plof_sig[k,1])
category <- as.character(plof_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- plof_sig[k,,drop=FALSE]
res_cond[1,3] <- "plof_cond"
}
plof_sig_cond <- rbind(plof_sig_cond,res_cond)
}
}
write.csv(plof_sig_cond,file=paste0(output_path,"plof_sig_cond.csv"))
### plof_ds
plof_ds_sig_cond <- c()
if(length(plof_ds_sig)!=0)
{
if((class(plof_ds_sig)[1]!="matrix")&(class(plof_ds_sig)[1]!="data.frame"))
{
plof_ds_sig <- matrix(plof_ds_sig,nrow=1)
}
for(k in 1:dim(plof_ds_sig)[1])
{
chr <- as.numeric(plof_ds_sig[k,2])
gene_name <- as.character(plof_ds_sig[k,1])
category <- as.character(plof_ds_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- plof_ds_sig[k,,drop=FALSE]
res_cond[1,3] <- "plof_ds_cond"
}
plof_ds_sig_cond <- rbind(plof_ds_sig_cond,res_cond)
}
}
write.csv(plof_ds_sig_cond,file=paste0(output_path,"plof_ds_sig_cond.csv"))
### missense
missense_sig_cond <- c()
if(length(missense_sig)!=0)
{
if((class(missense_sig)[1]!="matrix")&(class(missense_sig)[1]!="data.frame"))
{
missense_sig <- matrix(missense_sig,nrow=1)
}
for(k in 1:dim(missense_sig)[1])
{
chr <- as.numeric(missense_sig[k,2])
gene_name <- as.character(missense_sig[k,1])
category <- as.character(missense_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- missense_sig[k,,drop=FALSE]
res_cond[1,3] <- "missense_cond"
}
missense_sig_cond <- rbind(missense_sig_cond,res_cond)
}
}
write.csv(missense_sig_cond,file=paste0(output_path,"missense_sig_cond.csv"))
### disruptive_missense
disruptive_missense_sig_cond <- c()
if(length(disruptive_missense_sig)!=0)
{
if((class(disruptive_missense_sig)[1]!="matrix")&(class(disruptive_missense_sig)[1]!="data.frame"))
{
disruptive_missense_sig <- matrix(disruptive_missense_sig,nrow=1)
}
for(k in 1:dim(disruptive_missense_sig)[1])
{
chr <- as.numeric(disruptive_missense_sig[k,2])
gene_name <- as.character(disruptive_missense_sig[k,1])
category <- as.character(disruptive_missense_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- disruptive_missense_sig[k,,drop=FALSE]
res_cond[1,3] <- "disruptive_missense_cond"
}
disruptive_missense_sig_cond <- rbind(disruptive_missense_sig_cond,res_cond)
}
}
write.csv(disruptive_missense_sig_cond,file=paste0(output_path,"disruptive_missense_sig_cond.csv"))
# coding results
coding_sig_cond <- rbind(plof_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")],
missense_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,synonymous_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,plof_ds_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,disruptive_missense_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
write.csv(coding_sig_cond,file=paste0(output_path,"coding_sig_cond.csv"))
}
}
## manhattan plot
if(manhattan_plot)
{
### plof
results_STAAR <- results_plof_genome[,c(1,2,dim(results_plof_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof"
### plof_ds
results_STAAR <- results_plof_ds_genome[,c(1,2,dim(results_plof_ds_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof_ds"
### missense
if(!use_SPA)
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-6)]
}else
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-2)]
}
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "missense"
### disruptive_missense
results_STAAR <- results_disruptive_missense_genome[,c(1,2,dim(results_disruptive_missense_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "disruptive_missense"
### synonymous
results_STAAR <- results_synonymous_genome[,c(1,2,dim(results_synonymous_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "synonymous"
## ylim
coding_minp <- min(genes_info_manhattan[,(dim(genes_info_manhattan)[2]-4):dim(genes_info_manhattan)[2]])
min_y <- ceiling(-log10(coding_minp)) + 1
pch <- c(0,1,2,3,4)
figure1 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$plof,sig.level=alpha,pch=pch[1],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure2 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$plof_ds,sig.level=alpha,pch=pch[2],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure3 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$missense,sig.level=alpha,pch=pch[3],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure4 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$disruptive_missense,sig.level=alpha,pch=pch[4],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure5 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$synonymous,sig.level=alpha,pch=pch[5],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
print("Manhattan plot")
png(paste0(output_path,"gene_centric_coding_manhattan.png"), width = 9, height = 6, units = 'in', res = 600)
print(figure1)
print(figure2,newpage = FALSE)
print(figure3,newpage = FALSE)
print(figure4,newpage = FALSE)
print(figure5,newpage = FALSE)
dev.off()
}
## Q-Q plot
if(QQ_plot)
{
if(!manhattan_plot)
{
### plof
results_STAAR <- results_plof_genome[,c(1,2,dim(results_plof_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof"
### plof_ds
results_STAAR <- results_plof_ds_genome[,c(1,2,dim(results_plof_ds_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof_ds"
### missense
if(!use_SPA)
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-6)]
}else
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-2)]
}
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "missense"
### disruptive_missense
results_STAAR <- results_disruptive_missense_genome[,c(1,2,dim(results_disruptive_missense_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "disruptive_missense"
### synonymous
results_STAAR <- results_synonymous_genome[,c(1,2,dim(results_synonymous_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "synonymous"
## ylim
coding_minp <- min(genes_info_manhattan[,(dim(genes_info_manhattan)[2]-4):dim(genes_info_manhattan)[2]])
min_y <- ceiling(-log10(coding_minp)) + 1
}
print("Q-Q plot")
cex_point <- 1
png(paste0(output_path,"gene_centric_coding_qqplot.png"), width = 8, height = 8, units = 'in', res = 600)
### plof
## remove unconverged p-values
observed <- sort(genes_info_manhattan$plof[genes_info_manhattan$plof < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=0, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### plof_ds
## remove unconverged p-values
observed <- sort(genes_info_manhattan$plof_ds[genes_info_manhattan$plof_ds < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=1, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### missense
## remove unconverged p-values
observed <- sort(genes_info_manhattan$missense[genes_info_manhattan$missense < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=2, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### disruptive_missense
## remove unconverged p-values
observed <- sort(genes_info_manhattan$disruptive_missense[genes_info_manhattan$disruptive_missense < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=3, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### synonymous
## remove unconverged p-values
observed <- sort(genes_info_manhattan$synonymous[genes_info_manhattan$synonymous < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=4, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
legend("topleft",legend=c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"),ncol=1,bty="o",box.lwd=1,pch=0:4,cex=1.5,text.font=2)
dev.off()
}
}
xihaoli/STAARpipelineSummary documentation built on Oct. 20, 2024, 9:35 p.m.
R Package Documentation
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Defines functions Gene_Centric_Coding_Results_Summary
Documented in Gene_Centric_Coding_Results_Summary
#' Summarize gene-centric coding analysis results generated by \code{STAARpipeline} package and
#' perform conditional analysis for (unconditionally) significant coding masks by adjusting for a given list of known variants
#'
#' The \code{Gene_Centric_Coding_Results_Summary} function takes in the objects of gene-centric coding analysis results
#' generated by \code{STAARpipeline} package,
#' the object from fitting the null model, and the set of known variants to be adjusted for in conditional analysis
#' to summarize the gene-centric coding analysis results and analyze the conditional association between a quantitative/dichotomous phenotype
#' (including imbalanced case-control design) and
#' the rare variants in the unconditional significant coding masks.
#' @param agds_dir file directory of annotated GDS (aGDS) files for all chromosomes (1-22)
#' @param gene_centric_coding_jobs_num the number of gene-centric coding analysis results generated by \code{STAARpipeline} package.
#' @param input_path the directory of gene-centric coding analysis results that generated by \code{STAARpipeline} package.
#' @param output_path the directory for the output files.
#' @param gene_centric_results_name file name of gene-centric coding analysis results generated by \code{STAARpipeline} package.
#' @param obj_nullmodel an object from fitting the null model, which is either the output from \code{fit_nullmodel} function in the \code{STAARpipeline} package,
#' or the output from \code{fitNullModel} function in the \code{GENESIS} package and transformed using the \code{genesis2staar_nullmodel} function in the \code{STAARpipeline} package.
#' @param 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).
#' @param cMAC_cutoff the cutoff of the minimum number of the cumulative minor allele of variants in the masks
#' when summarizing the results (default = 0).
#' @param method_cond a character value indicating the method for conditional analysis.
#' \code{optimal} refers to regressing residuals from the null model on \code{known_loci}
#' as well as all covariates used in fitting the null model (fully adjusted) and taking the residuals;
#' \code{naive} refers to regressing residuals from the null model on \code{known_loci}
#' and taking the residuals (default = \code{optimal}).
#' @param rare_maf_cutoff the cutoff of maximum minor allele frequency in
#' defining rare variants (default = 0.01).
#' @param QC_label channel name of the QC label in the GDS/aGDS file (default = "annotation/filter").
#' @param variant_type type of variant included in the analysis. Choices include "SNV", "Indel", or "variant" (default = "SNV").
#' @param geno_missing_imputation method of handling missing genotypes. Either "mean" or "minor" (default = "mean").
#' @param Annotation_dir channel name of the annotations in the aGDS file \cr (default = "annotation/info/FunctionalAnnotation").
#' @param Annotation_name_catalog a data frame containing the name and the corresponding channel name in the aGDS file.
#' @param Use_annotation_weights use annotations as weights or not (default = FALSE).
#' @param Annotation_name a vector of annotation names used in STAAR (default = NULL).
#' @param alpha p-value threshold of significant results (default = 2.5E-06).
#' @param manhattan_plot output manhattan plot or not (default = FALSE).
#' @param QQ_plot output Q-Q plot or not (default = FALSE).
#' @param cond_null_model_name the null model name for conditional analysis in the SPA setting, only used for imbalanced case-control setting (default = NULL).
#' @param cond_null_model_dir the directory of storing the null model for conditional analysis in the SPA setting, only used for imbalanced case-control setting (default = NULL).
#' @param 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).
#' @param p_filter_cutoff threshold for the p-value recalculation using the SPA method, only used for imbalanced case-control setting (default = 0.05).
#' @return The function returns the following analysis results:
#' @return \code{coding_sig.csv}: a matrix that summarizes the unconditional significant coding masks detected by STAAR-O or STAAR-B in imbalanced case-control setting (STAAR-O/-B pvalue smaller than the threshold alpha),
#' including gene name ("Gene name"), chromosome ("chr"), coding functional category ("Category"), number of variants ("#SNV"),
#' and unconditional p-values of set-based tests SKAT ("SKAT(1,25)"), Burden ("Burden(1,1)"), ACAT-V ("ACAT-V(1,25)") and STAAR-O ("STAAR-O")
#' or unconditional p-values of set-based tests Burden ("Burden(1,1)") and STAAR-B ("STAAR-B") for imbalanced case-control setting.
#' @return \code{coding_sig_cond.csv}: a matrix that summarized the conditional analysis results of unconditional significant coding masks detected by STAAR-O or STAAR-B in imbalanced case-control setting (available if known_loci is not a NULL),
#' including gene name ("Gene name"), chromosome ("chr"), coding functional category ("Category"), number of variants ("#SNV"),
#' and conditional p-values of set-based tests SKAT ("SKAT(1,25)"), Burden ("Burden(1,1)"), ACAT-V ("ACAT-V(1,25)") and STAAR-O ("STAAR-O")
#' or conditional p-values of set-based tests Burden ("Burden(1,1)") and STAAR-B ("STAAR-B") for imbalanced case-control setting.
#' @return \code{results_plof_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the putative loss of function variants (plof) for all protein-coding genes across the genome.
#' @return \code{plof_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof masks.
#' @return \code{plof_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof masks (available if known_loci is not a NULL).
#' @return \code{results_plof_ds_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the putative loss of function variants and disruptive missense variants (plof_ds) for all protein-coding genes across the genome.
#' @return \code{plof_ds_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof_ds masks.
#' @return \code{plof_ds_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant plof_ds masks (available if known_loci is not a NULL).
#' @return \code{results_disruptive_missense_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the disruptive missense variants (disruptive_missense) for all protein-coding genes across the genome.
#' @return \code{disruptive_missense_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant disruptive_missense masks.
#' @return \code{disruptive_missense_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant disruptive_missense masks (available if known_loci is not a NULL).
#' @return \code{results_missense_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the missense variants (missense) for all protein-coding genes across the genome.
#' @return \code{missense_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant missense masks.
#' @return \code{missense_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant missense masks (available if known_loci is not a NULL).
#' @return \code{results_synonymous_genome.Rdata}: a matrix contains the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the coding mask defined by the synonymous variants (synonymous) for all protein-coding genes across the genome.
#' @return \code{synonymous_sig.csv}: a matrix contains the unconditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant synonymous masks.
#' @return \code{synonymous_sig_cond.csv}: a matrix contains the conditional STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) of the unconditional significant synonymous masks (available if known_loci is not a NULL).
#' @return manhattan plot (optional) and Q-Q plot (optional) of the gene-centric coding analysis results.
#' @references Li, Z., Li, X., et al. (2022). A framework for detecting
#' noncoding rare-variant associations of large-scale whole-genome sequencing
#' studies. \emph{Nature Methods}, \emph{19}(12), 1599-1611.
#' (\href{https://doi.org/10.1038/s41592-022-01640-x}{pub})
#' @export
Gene_Centric_Coding_Results_Summary <- function(agds_dir,gene_centric_coding_jobs_num,input_path,output_path,gene_centric_results_name,
obj_nullmodel,known_loci=NULL,cMAC_cutoff=0,
method_cond=c("optimal","naive"),rare_maf_cutoff=0.01,
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=FALSE,Annotation_name=NULL,
alpha=2.5E-06,manhattan_plot=FALSE,QQ_plot=FALSE,
cond_null_model_name=NULL,cond_null_model_dir=NULL,
SPA_p_filter=FALSE,p_filter_cutoff=0.05){
## evaluate choices
method_cond <- match.arg(method_cond)
variant_type <- match.arg(variant_type)
geno_missing_imputation <- match.arg(geno_missing_imputation)
## SPA status
if(!is.null(obj_nullmodel$use_SPA))
{
use_SPA <- obj_nullmodel$use_SPA
}else
{
use_SPA <- FALSE
}
#######################################################
# summarize unconditional analysis results
#######################################################
results_coding_genome <- c()
for(kk in 1:gene_centric_coding_jobs_num)
{
print(kk)
results_coding <- get(load(paste0(input_path,gene_centric_results_name,"_",kk,".Rdata")))
results_coding_genome <- c(results_coding_genome,results_coding)
}
results_plof_genome <- c()
results_plof_ds_genome <- c()
results_missense_genome <- c()
results_disruptive_missense_genome <- c()
results_synonymous_genome <- c()
for(kk in 1:length(results_coding_genome))
{
results <- results_coding_genome[[kk]]
if(is.null(results)==FALSE)
{
### plof
if(results[3]=="plof")
{
results_plof_genome <- rbind(results_plof_genome,results)
}
### plof_ds
if(results[3]=="plof_ds")
{
results_plof_ds_genome <- rbind(results_plof_ds_genome,results)
}
### missense
if(results[3]=="missense")
{
results_missense_genome <- rbind(results_missense_genome,results)
}
### disruptive_missense
if(results[3]=="disruptive_missense")
{
results_disruptive_missense_genome <- rbind(results_disruptive_missense_genome,results)
}
### synonymous
if(results[3]=="synonymous")
{
results_synonymous_genome <- rbind(results_synonymous_genome,results)
}
}
if(kk%%1000==0)
{
print(kk)
}
}
###### cMAC_cutoff
# plof
results_plof_genome <- results_plof_genome[results_plof_genome[,"cMAC"]>cMAC_cutoff,]
# plof + disruptive missense
results_plof_ds_genome <- results_plof_ds_genome[results_plof_ds_genome[,"cMAC"]>cMAC_cutoff,]
# missense
results_missense_genome <- results_missense_genome[results_missense_genome[,"cMAC"]>cMAC_cutoff,]
# disruptive missense
results_disruptive_missense_genome <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"cMAC"]>cMAC_cutoff,]
# synonymous
results_synonymous_genome <- results_synonymous_genome[results_synonymous_genome[,"cMAC"]>cMAC_cutoff,]
### recalculate missense pvalue
if(cMAC_cutoff > 0)
{
genes_name_disruptive_missense <- as.vector(unlist(results_disruptive_missense_genome[,1]))
genes_name_missense <- as.vector(unlist(results_missense_genome[,1]))
recal_id <- (1:dim(results_missense_genome)[1])[(!genes_name_missense%in%genes_name_disruptive_missense)]
for(kk in recal_id)
{
print(kk)
results_m <- results_missense_genome[kk,]
if(use_SPA)
{
## disruptive missense cMAC < cut_off, set p-value to 1
results_missense_genome[kk,"Burden(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"Burden(1,1)-Disruptive"] <- 1
apc_num <- (length(results_m)-10)/2
p_seq <- c(1:apc_num,1:apc_num+(apc_num+1))
## calculate STAAR-B
pvalues_sub <- as.numeric(results_m[6:length(results_m)][p_seq])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B"] <- 1
}
}
results_missense_genome[kk,"STAAR-B"] <- results_m["STAAR-B"]
## calculate STAAR-B(1,25)
pvalues_sub <- as.numeric(results_m[6:length(results_m)][c(1:apc_num)])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B(1,25)"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B(1,25)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,25)"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B(1,25)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,25)"] <- 1
}
}
results_missense_genome[kk,"STAAR-B(1,25)"] <- results_m["STAAR-B(1,25)"]
## calculate STAAR-B(1,1)
pvalues_sub <- as.numeric(results_m[6:length(results_m)][c(1:apc_num+(apc_num+1))])
if(sum(is.na(pvalues_sub))>0)
{
if(sum(is.na(pvalues_sub))==length(pvalues_sub))
{
results_m["STAAR-B(1,1)"] <- 1
}else
{
## not all NAs
pvalues_sub <- pvalues_sub[!is.na(pvalues_sub)]
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
## not all ones
results_m["STAAR-B(1,1)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,1)"] <- 1
}
}
}else
{
if(sum(pvalues_sub[pvalues_sub<1])>0)
{
results_m["STAAR-B(1,1)"] <- CCT(pvalues_sub[pvalues_sub<1])
}else
{
results_m["STAAR-B(1,1)"] <- 1
}
}
results_missense_genome[kk,"STAAR-B(1,1)"] <- results_m["STAAR-B(1,1)"]
}else
{
## disruptive missense cMAC < cut_off, set p-value to 1
results_missense_genome[kk,"Burden(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"Burden(1,1)-Disruptive"] <- 1
results_missense_genome[kk,"SKAT(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"SKAT(1,1)-Disruptive"] <- 1
results_missense_genome[kk,"ACAT-V(1,25)-Disruptive"] <- 1
results_missense_genome[kk,"ACAT-V(1,1)-Disruptive"] <- 1
apc_num <- (length(results_m)-19)/6
p_seq <- c(1:apc_num,1:apc_num+(apc_num+1),1:apc_num+2*(apc_num+1),1:apc_num+3*(apc_num+1),1:apc_num+4*(apc_num+1),1:apc_num+5*(apc_num+1))
results_m["STAAR-O"] <- CCT(as.numeric(results_m[6:length(results_m)][p_seq]))
results_m["STAAR-S(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num)]))
results_m["STAAR-S(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+(apc_num+1))]))
results_m["STAAR-B(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+2*(apc_num+1))]))
results_m["STAAR-B(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+3*(apc_num+1))]))
results_m["STAAR-A(1,25)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+4*(apc_num+1))]))
results_m["STAAR-A(1,1)"] <- CCT(as.numeric(results_m[6:length(results_m)][c(1:apc_num+5*(apc_num+1))]))
}
}
}
###### whole-genome results
# plof
save(results_plof_genome,file=paste0(output_path,"plof.Rdata"))
# plof + disruptive missense
save(results_plof_ds_genome,file=paste0(output_path,"plof_ds.Rdata"))
# missense
save(results_missense_genome,file=paste0(output_path,"missense.Rdata"))
# disruptive missense
save(results_disruptive_missense_genome,file=paste0(output_path,"disruptive_missense.Rdata"))
# synonymous
save(results_synonymous_genome,file=paste0(output_path,"synonymous.Rdata"))
if(use_SPA)
{
###### significant results
# plof
plof_sig <- results_plof_genome[results_plof_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(plof_sig,file=paste0(output_path,"plof_sig.csv"))
# missense
missense_sig <- results_missense_genome[results_missense_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(missense_sig,file=paste0(output_path,"missense_sig.csv"))
# synonymous
synonymous_sig <- results_synonymous_genome[results_synonymous_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(synonymous_sig,file=paste0(output_path,"synonymous_sig.csv"))
# plof_ds
plof_ds_sig <- results_plof_ds_genome[results_plof_ds_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(plof_ds_sig,file=paste0(output_path,"plof_ds_sig.csv"))
# disruptive_missense
disruptive_missense_sig <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"STAAR-B"]<alpha,,drop=FALSE]
write.csv(disruptive_missense_sig,file=paste0(output_path,"disruptive_missense_sig.csv"))
# coding results
coding_sig <- rbind(plof_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")],
missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,synonymous_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,plof_ds_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig <- rbind(coding_sig,disruptive_missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
write.csv(coding_sig,file=paste0(output_path,"coding_sig.csv"))
}else
{
# plof
plof_sig <- results_plof_genome[results_plof_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(plof_sig,file=paste0(output_path,"plof_sig.csv"))
# missense
missense_sig <- results_missense_genome[results_missense_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(missense_sig,file=paste0(output_path,"missense_sig.csv"))
# synonymous
synonymous_sig <- results_synonymous_genome[results_synonymous_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(synonymous_sig,file=paste0(output_path,"synonymous_sig.csv"))
# plof_ds
plof_ds_sig <- results_plof_ds_genome[results_plof_ds_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(plof_ds_sig,file=paste0(output_path,"plof_ds_sig.csv"))
# disruptive_missense
disruptive_missense_sig <- results_disruptive_missense_genome[results_disruptive_missense_genome[,"STAAR-O"]<alpha,,drop=FALSE]
write.csv(disruptive_missense_sig,file=paste0(output_path,"disruptive_missense_sig.csv"))
# coding results
coding_sig <- rbind(plof_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")],
missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,synonymous_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,plof_ds_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig <- rbind(coding_sig,disruptive_missense_sig[,c("Gene name","Chr","Category","#SNV","cMAC","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
write.csv(coding_sig,file=paste0(output_path,"coding_sig.csv"))
}
#######################################################
# conditional analysis
#######################################################
if(length(known_loci)!=0)
{
if(!use_SPA)
{
### plof
plof_sig_cond <- c()
if(length(plof_sig)!=0)
{
if((class(plof_sig)[1]!="matrix")&(class(plof_sig)[1]!="data.frame"))
{
plof_sig <- matrix(plof_sig,nrow=1)
}
for(k in 1:dim(plof_sig)[1])
{
chr <- as.numeric(plof_sig[k,2])
gene_name <- as.character(plof_sig[k,1])
category <- as.character(plof_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
plof_sig_cond <- rbind(plof_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(plof_sig_cond,file=paste0(output_path,"plof_sig_cond.csv"))
### missense
missense_sig_cond <- c()
if(length(missense_sig)!=0)
{
if((class(missense_sig)[1]!="matrix")&(class(missense_sig)[1]!="data.frame"))
{
missense_sig <- matrix(missense_sig,nrow=1)
}
for(k in 1:dim(missense_sig)[1])
{
chr <- as.numeric(missense_sig[k,2])
gene_name <- as.character(missense_sig[k,1])
category <- as.character(missense_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
missense_sig_cond <- rbind(missense_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(missense_sig_cond,file=paste0(output_path,"missense_sig_cond.csv"))
### synonymous
synonymous_sig_cond <- c()
if(length(synonymous_sig)!=0)
{
if((class(synonymous_sig)[1]!="matrix")&(class(synonymous_sig)[1]!="data.frame"))
{
synonymous_sig <- matrix(synonymous_sig,nrow=1)
}
for(k in 1:dim(synonymous_sig)[1])
{
chr <- as.numeric(synonymous_sig[k,2])
gene_name <- as.character(synonymous_sig[k,1])
category <- as.character(synonymous_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
synonymous_sig_cond <- rbind(synonymous_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(synonymous_sig_cond,file=paste0(output_path,"synonymous_sig_cond.csv"))
### plof_ds
plof_ds_sig_cond <- c()
if(length(plof_ds_sig)!=0)
{
if((class(plof_ds_sig)[1]!="matrix")&(class(plof_ds_sig)[1]!="data.frame"))
{
plof_ds_sig <- matrix(plof_ds_sig,nrow=1)
}
for(k in 1:dim(plof_ds_sig)[1])
{
chr <- as.numeric(plof_ds_sig[k,2])
gene_name <- as.character(plof_ds_sig[k,1])
category <- as.character(plof_ds_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
plof_ds_sig_cond <- rbind(plof_ds_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(plof_ds_sig_cond,file=paste0(output_path,"plof_ds_sig_cond.csv"))
### disruptive_missense
disruptive_missense_sig_cond <- c()
if(length(disruptive_missense_sig)!=0)
{
if((class(disruptive_missense_sig)[1]!="matrix")&(class(disruptive_missense_sig)[1]!="data.frame"))
{
disruptive_missense_sig <- matrix(disruptive_missense_sig,nrow=1)
}
for(k in 1:dim(disruptive_missense_sig)[1])
{
chr <- as.numeric(disruptive_missense_sig[k,2])
gene_name <- as.character(disruptive_missense_sig[k,1])
category <- as.character(disruptive_missense_sig[k,3])
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
res_cond <- Gene_Centric_Coding_cond(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name)
disruptive_missense_sig_cond <- rbind(disruptive_missense_sig_cond,res_cond)
seqClose(genofile)
}
}
write.csv(disruptive_missense_sig_cond,file=paste0(output_path,"disruptive_missense_sig_cond.csv"))
## coding cond
coding_sig_cond <- rbind(plof_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")],
missense_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,synonymous_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,plof_ds_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
coding_sig_cond <- rbind(coding_sig_cond,disruptive_missense_sig_cond[,c("Gene name","Chr","Category","#SNV","SKAT(1,25)","Burden(1,1)","ACAT-V(1,25)","STAAR-O")])
write.csv(coding_sig_cond,file=paste0(output_path,"coding_sig_cond.csv"))
}else
{
### synonymous
synonymous_sig_cond <- c()
if(length(synonymous_sig)!=0)
{
if((class(synonymous_sig)[1]!="matrix")&(class(synonymous_sig)[1]!="data.frame"))
{
synonymous_sig <- matrix(synonymous_sig,nrow=1)
}
for(k in 1:dim(synonymous_sig)[1])
{
chr <- as.numeric(synonymous_sig[k,2])
gene_name <- as.character(synonymous_sig[k,1])
category <- as.character(synonymous_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- synonymous_sig[k,,drop=FALSE]
res_cond[1,3] <- "synonymous_cond"
}
synonymous_sig_cond <- rbind(synonymous_sig_cond,res_cond)
}
}
write.csv(synonymous_sig_cond,file=paste0(output_path,"synonymous_sig_cond.csv"))
### plof
plof_sig_cond <- c()
if(length(plof_sig)!=0)
{
if((class(plof_sig)[1]!="matrix")&(class(plof_sig)[1]!="data.frame"))
{
plof_sig <- matrix(plof_sig,nrow=1)
}
for(k in 1:dim(plof_sig)[1])
{
chr <- as.numeric(plof_sig[k,2])
gene_name <- as.character(plof_sig[k,1])
category <- as.character(plof_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- plof_sig[k,,drop=FALSE]
res_cond[1,3] <- "plof_cond"
}
plof_sig_cond <- rbind(plof_sig_cond,res_cond)
}
}
write.csv(plof_sig_cond,file=paste0(output_path,"plof_sig_cond.csv"))
### plof_ds
plof_ds_sig_cond <- c()
if(length(plof_ds_sig)!=0)
{
if((class(plof_ds_sig)[1]!="matrix")&(class(plof_ds_sig)[1]!="data.frame"))
{
plof_ds_sig <- matrix(plof_ds_sig,nrow=1)
}
for(k in 1:dim(plof_ds_sig)[1])
{
chr <- as.numeric(plof_ds_sig[k,2])
gene_name <- as.character(plof_ds_sig[k,1])
category <- as.character(plof_ds_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- plof_ds_sig[k,,drop=FALSE]
res_cond[1,3] <- "plof_ds_cond"
}
plof_ds_sig_cond <- rbind(plof_ds_sig_cond,res_cond)
}
}
write.csv(plof_ds_sig_cond,file=paste0(output_path,"plof_ds_sig_cond.csv"))
### missense
missense_sig_cond <- c()
if(length(missense_sig)!=0)
{
if((class(missense_sig)[1]!="matrix")&(class(missense_sig)[1]!="data.frame"))
{
missense_sig <- matrix(missense_sig,nrow=1)
}
for(k in 1:dim(missense_sig)[1])
{
chr <- as.numeric(missense_sig[k,2])
gene_name <- as.character(missense_sig[k,1])
category <- as.character(missense_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- missense_sig[k,,drop=FALSE]
res_cond[1,3] <- "missense_cond"
}
missense_sig_cond <- rbind(missense_sig_cond,res_cond)
}
}
write.csv(missense_sig_cond,file=paste0(output_path,"missense_sig_cond.csv"))
### disruptive_missense
disruptive_missense_sig_cond <- c()
if(length(disruptive_missense_sig)!=0)
{
if((class(disruptive_missense_sig)[1]!="matrix")&(class(disruptive_missense_sig)[1]!="data.frame"))
{
disruptive_missense_sig <- matrix(disruptive_missense_sig,nrow=1)
}
for(k in 1:dim(disruptive_missense_sig)[1])
{
chr <- as.numeric(disruptive_missense_sig[k,2])
gene_name <- as.character(disruptive_missense_sig[k,1])
category <- as.character(disruptive_missense_sig[k,3])
if(file.exists(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
{
gds.path <- agds_dir[chr]
genofile <- seqOpen(gds.path)
obj_nullmodel_cond <- get(load(paste0(cond_null_model_dir,cond_null_model_name,".chr",chr,".Rdata")))
res_cond <- Gene_Centric_Coding_cond_spa(chr=chr,gene_name=gene_name,category=category,genofile=genofile,
obj_nullmodel=obj_nullmodel_cond,known_loci=known_loci,rare_maf_cutoff=rare_maf_cutoff,
variant_type=variant_type,geno_missing_imputation=geno_missing_imputation,QC_label=QC_label,
Annotation_dir=Annotation_dir,Annotation_name_catalog=Annotation_name_catalog,
Use_annotation_weights=Use_annotation_weights,Annotation_name=Annotation_name,
SPA_p_filter=SPA_p_filter,p_filter_cutoff=p_filter_cutoff)
seqClose(genofile)
}else
{
res_cond <- disruptive_missense_sig[k,,drop=FALSE]
res_cond[1,3] <- "disruptive_missense_cond"
}
disruptive_missense_sig_cond <- rbind(disruptive_missense_sig_cond,res_cond)
}
}
write.csv(disruptive_missense_sig_cond,file=paste0(output_path,"disruptive_missense_sig_cond.csv"))
# coding results
coding_sig_cond <- rbind(plof_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")],
missense_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,synonymous_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,plof_ds_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
coding_sig_cond <- rbind(coding_sig_cond,disruptive_missense_sig_cond[,c("Gene name","Chr","Category","#SNV","cMAC","Burden(1,1)","STAAR-B")])
write.csv(coding_sig_cond,file=paste0(output_path,"coding_sig_cond.csv"))
}
}
## manhattan plot
if(manhattan_plot)
{
### plof
results_STAAR <- results_plof_genome[,c(1,2,dim(results_plof_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof"
### plof_ds
results_STAAR <- results_plof_ds_genome[,c(1,2,dim(results_plof_ds_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof_ds"
### missense
if(!use_SPA)
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-6)]
}else
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-2)]
}
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "missense"
### disruptive_missense
results_STAAR <- results_disruptive_missense_genome[,c(1,2,dim(results_disruptive_missense_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "disruptive_missense"
### synonymous
results_STAAR <- results_synonymous_genome[,c(1,2,dim(results_synonymous_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "synonymous"
## ylim
coding_minp <- min(genes_info_manhattan[,(dim(genes_info_manhattan)[2]-4):dim(genes_info_manhattan)[2]])
min_y <- ceiling(-log10(coding_minp)) + 1
pch <- c(0,1,2,3,4)
figure1 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$plof,sig.level=alpha,pch=pch[1],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure2 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$plof_ds,sig.level=alpha,pch=pch[2],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure3 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$missense,sig.level=alpha,pch=pch[3],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure4 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$disruptive_missense,sig.level=alpha,pch=pch[4],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
figure5 <- manhattan_plot(genes_info_manhattan[,2], (genes_info_manhattan[,3]+genes_info_manhattan[,4])/2, genes_info_manhattan$synonymous,sig.level=alpha,pch=pch[5],col = c("blue4", "orange3"),ylim=c(0,min_y),
auto.key=T,key=list(space="top", columns=5, title="Functional Category", cex.title=1, points=TRUE,pch=pch,text=list(c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"))))
print("Manhattan plot")
png(paste0(output_path,"gene_centric_coding_manhattan.png"), width = 9, height = 6, units = 'in', res = 600)
print(figure1)
print(figure2,newpage = FALSE)
print(figure3,newpage = FALSE)
print(figure4,newpage = FALSE)
print(figure5,newpage = FALSE)
dev.off()
}
## Q-Q plot
if(QQ_plot)
{
if(!manhattan_plot)
{
### plof
results_STAAR <- results_plof_genome[,c(1,2,dim(results_plof_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof"
### plof_ds
results_STAAR <- results_plof_ds_genome[,c(1,2,dim(results_plof_ds_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "plof_ds"
### missense
if(!use_SPA)
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-6)]
}else
{
results_STAAR <- results_missense_genome[,c(1,2,dim(results_missense_genome)[2]-2)]
}
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "missense"
### disruptive_missense
results_STAAR <- results_disruptive_missense_genome[,c(1,2,dim(results_disruptive_missense_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "disruptive_missense"
### synonymous
results_STAAR <- results_synonymous_genome[,c(1,2,dim(results_synonymous_genome)[2])]
results_m <- c()
for(i in 1:dim(results_STAAR)[2])
{
results_m <- cbind(results_m,unlist(results_STAAR[,i]))
}
colnames(results_m) <- colnames(results_STAAR)
results_m <- data.frame(results_m,stringsAsFactors = FALSE)
results_m[,2] <- as.numeric(results_m[,2])
results_m[,3] <- as.numeric(results_m[,3])
genes_info_manhattan <- dplyr::left_join(genes_info_manhattan,results_m,by=c("chromosome_name"="Chr","hgnc_symbol"="Gene.name"))
genes_info_manhattan[is.na(genes_info_manhattan)] <- 1
colnames(genes_info_manhattan)[dim(genes_info_manhattan)[2]] <- "synonymous"
## ylim
coding_minp <- min(genes_info_manhattan[,(dim(genes_info_manhattan)[2]-4):dim(genes_info_manhattan)[2]])
min_y <- ceiling(-log10(coding_minp)) + 1
}
print("Q-Q plot")
cex_point <- 1
png(paste0(output_path,"gene_centric_coding_qqplot.png"), width = 8, height = 8, units = 'in', res = 600)
### plof
## remove unconverged p-values
observed <- sort(genes_info_manhattan$plof[genes_info_manhattan$plof < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=0, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### plof_ds
## remove unconverged p-values
observed <- sort(genes_info_manhattan$plof_ds[genes_info_manhattan$plof_ds < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=1, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### missense
## remove unconverged p-values
observed <- sort(genes_info_manhattan$missense[genes_info_manhattan$missense < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=2, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### disruptive_missense
## remove unconverged p-values
observed <- sort(genes_info_manhattan$disruptive_missense[genes_info_manhattan$disruptive_missense < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=3, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
### synonymous
## remove unconverged p-values
observed <- sort(genes_info_manhattan$synonymous[genes_info_manhattan$synonymous < 1])
lobs <- -(log10(observed))
expected <- c(1:length(observed))
lexp <- -(log10(expected / (length(expected)+1)))
par(new=T)
par(mar=c(5,6,4,4))
plot(lexp,lobs,pch=4, cex=cex_point, xlim = c(0, 5), ylim = c(0, min_y),
xlab = expression(Expected ~ ~-log[10](italic(p))), ylab = expression(Observed ~ ~-log[10](italic(p))),
font.lab=2,cex.lab=2,cex.axis=2,font.axis=2)
abline(0, 1, col="red",lwd=2)
legend("topleft",legend=c("pLoF","pLoF+D","Missense","Disruptive Missense","Synonymous"),ncol=1,bty="o",box.lwd=1,pch=0:4,cex=1.5,text.font=2)
dev.off()
}
}
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