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rbcf

R Bindings for htslib/bcf+vcf

Build Status

Last commit

INSTALL

Requirements: R, git, curl-dev,

git clone "https://github.com/lindenb/rbcf"

cd rbcf

make

Author

Pierre Lindenbaum PhD. Institut du Thorax. Nantes, France. @yokofakun

Examples

Show Htslib and Rbcf versions

Code:

# load the library
library(rbcf)
#print the version of the associated htslib 
paste("HTSLIB:",htslib.version())
#print the version of rbcf
paste("RBCF:",rcbf.version())

Output:

[1] "HTSLIB: 1.10.2"
[1] "RBCF: 0.0-1"

Open and close a VCF file

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/rotavirus_rf.01.vcf",FALSE)
# error (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# dispose the vcf reader
bcf.close(fp)
print("Done.")

Output:

[1] TRUE
[1] "Done."

Print the INFOs in the VCF header

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/rotavirus_rf.01.vcf",FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# print INFO
bcf.infos(fp)
# dispose the vcf reader
bcf.close(fp)
# print the table

Output:

         ID Number    Type
INDEL INDEL      0    Flag
IDV     IDV      1 Integer
IMF     IMF      1   Float
DP       DP      1 Integer
VDB     VDB      1   Float
RPB     RPB      1   Float
MQB     MQB      1   Float
BQB     BQB      1   Float
MQSB   MQSB      1   Float
SGB     SGB      1   Float
MQ0F   MQ0F      1   Float
ICB     ICB      1   Float
HOB     HOB      1   Float
AC       AC      A Integer
AN       AN      1 Integer
DP4     DP4      4 Integer
MQ       MQ      1 Integer
                                                                                         Descri(...)
INDEL                                                      "Indicates that the variant is an IN(...)
IDV                                                    "Maximum number of reads supporting an i(...)
IMF                                                  "Maximum fraction of reads supporting an i(...)
DP                                                                                  "Raw read d(...)
VDB   "Variant Distance Bias for filtering splice-site artefacts in RNA-seq data (bigger is bet(...)
RPB                                   "Mann-Whitney U test of Read Position Bias (bigger is bet(...)
MQB                                 "Mann-Whitney U test of Mapping Quality Bias (bigger is bet(...)
BQB                                    "Mann-Whitney U test of Base Quality Bias (bigger is bet(...)
MQSB                      "Mann-Whitney U test of Mapping Quality vs Strand Bias (bigger is bet(...)
SGB                                                                      "Segregation based met(...)
MQ0F                                                     "Fraction of MQ0 reads (smaller is bet(...)
ICB                                        "Inbreeding Coefficient Binomial test (bigger is bet(...)
HOB                                          "Bias in the number of HOMs number (smaller is bet(...)
AC                      "Allele count in genotypes for each ALT allele, in the same order as li(...)
AN                                                     "Total number of alleles in called genot(...)
DP4            "Number of high-quality ref-forward , ref-reverse, alt-forward and alt-reverse b(...)
MQ                                                                         "Average mapping qua(...)
[1] TRUE

Print the FORMATs in the VCF header

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/rotavirus_rf.01.vcf",FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# print FORMAT
bcf.formats(fp)
# dispose the vcf reader
bcf.close(fp)

Output:

   ID Number    Type                                 Description
PL PL      G Integer "List of Phred-scaled genotype likelihoods"
GT GT      1  String                                  "Genotype"
[1] TRUE

Print the FILTERs in the VCF header

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/gnomad.exomes.r2.0.1.sites.bcf",FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# print FILTERs
bcf.filters(fp)
# dispose the vcf reader
bcf.close(fp)

Output:

                             ID
PASS                       PASS
AC0                         AC0
InbreedingCoeff InbreedingCoeff
LCR                         LCR
RF                           RF
SEGDUP                   SEGDUP
                                                                                               (...)
PASS                                                                                           (...)
AC0             "Allele Count is zero (i.e. no high-confidence genotype (GQ >= 20, DP >= 10, AB(...)
InbreedingCoeff                                                                                (...)
LCR                                                                                        "In (...)
RF                                                  "Failed random forests filters (SNV cutoff (...)
SEGDUP                                                                              "In a segme(...)
[1] TRUE

Print the Samples in the VCF header

The samples are defined in the '#CHROM' line of the VCF

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/rotavirus_rf.01.vcf",FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# print the number of samples
paste("Number of samples:",bcf.nsamples(fp))
# get the name for the 1st sample
paste("First sample:",bcf.sample.at(fp,1))
# get the 1-based index for the samples
bcf.sample2index(fp,c("S1","S2","S3","missing"))
# get all the samples
bcf.samples(fp)
# dispose the vcf reader
bcf.close(fp)

Output:

[1] "Number of samples: 5"
[1] "First sample: S1"
     S1      S2      S3 missing 
      1       2       3       0 
[1] "S1" "S2" "S3" "S4" "S5"
[1] TRUE

Print the Dictionary in the VCF header

Code:

# load rbcf
library(rbcf)
# we don't need the index for this file
fp <- bcf.open("./data/rotavirus_rf.01.vcf",FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# print the dictionary
bcf.dictionary(fp)
# dispose the vcf reader
bcf.close(fp)

Output:

     chrom size
RF01  RF01 3302
RF02  RF02 2687
RF03  RF03 2592
RF04  RF04 2362
RF05  RF05 1579
RF06  RF06 1356
RF07  RF07 1074
RF08  RF08 1059
RF09  RF09 1062
RF10  RF10  751
RF11  RF11  666
[1] TRUE

Print the Indexed Chromosomes

Code:

# load rbcf
library(rbcf)
# Open the indexed VCF
fp <- bcf.open("./data/rotavirus_rf.02.vcf.gz")
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# get the indexed contigs
bcf.contigs(fp)
# dispose the vcf reader
bcf.close(fp)

Output:

 [1] "RF01" "RF02" "RF03" "RF04" "RF05" "RF06" "RF07" "RF08" "RF09" "RF10"
[11] "RF11"
[1] TRUE

Scanning the variants

Code:

# load rbcf
library(rbcf)

# create a function counting variants in a VCF
count.variants<-function(filename) {
	# we don't need the index for this file
	fp <- bcf.open(filename,FALSE)
	# error on opening
	if(is.null(fp)) return(-1)
	# number of variants
	n<-0
	# loop while we can read a variant
	while(!is.null(vc<-bcf.next(fp))) {
		# increment the count
		n<-n+1
	}
	# dispose the vcf reader
	bcf.close(fp)
	# return the number of variant
	n
}

# filenames
vcfs<-c(
	"./data/gnomad.exomes.r2.0.1.sites.bcf",
	"./data/rotavirus_rf.01.vcf",
	"./data/rotavirus_rf.02.vcf.gz",
	"./data/rotavirus_rf.03.vcf.gz",
	"./data/rotavirus_rf.04.bcf"
	)
# print the number of variants for each vcf
for(f in vcfs) {
	cat(paste(f," ",count.variants(f),"\n"))
	}

Output:

./data/gnomad.exomes.r2.0.1.sites.bcf   50 
./data/rotavirus_rf.01.vcf   45 
./data/rotavirus_rf.02.vcf.gz   45 
./data/rotavirus_rf.03.vcf.gz   45 
./data/rotavirus_rf.04.bcf   45 

Scanning the variants

Code:

# load rbcf
library(rbcf)

# create a function counting variants in a VCF
count.variants<-function(filename,predicate) {
	# we don't need the index for this file
	fp <- bcf.open(filename,FALSE)
	# error on opening
	if(is.null(fp)) return(-1)
	# number of variants
	n<-0
	# loop while we can read a variant
	while(!is.null(vc<-bcf.next(fp))) {
		# test the variant
		if(predicate(vc)) {
			# increment the count
			n<-n+1
			}
	}
	# dispose the vcf reader
	bcf.close(fp)
	# return the number of variant
	n
}

# A vcf
filename <- "./data/gnomad.exomes.r2.0.1.sites.bcf"
# filters
filters<-list(
	list("desc"="accept all","predicate"=function(ctx) {TRUE} ),
	list("desc"="accept none","predicate"=function(ctx) {FALSE} ),
	list("desc"="CHROM is '1'","predicate"=function(ctx) { variant.contig(ctx)=="1"} ),
	list("desc"="POS is even","predicate"=function(ctx) { (variant.pos(ctx)%%2)==1} ),
	list("desc"="PASS filter","predicate"=function(ctx) {!variant.is.filtered(ctx)} ),
	list("desc"="count(FILTER)>1","predicate"=function(ctx) {length(variant.filters(ctx))>1} ),
	list("desc"="FILTER contains SEGDUP","predicate"=function(ctx) {variant.has.filter(ctx,"SEGDUP")} ),
	list("desc"="SNP","predicate"=function(ctx) {variant.is.snp(ctx)} ),
	list("desc"="POS!=END","predicate"=function(ctx) { variant.pos(ctx)!=variant.end(ctx)} ),
	list("desc"="not diallelic","predicate"=function(ctx) {variant.nalleles(ctx)!=2} ),
	list("desc"="REF is 'A'","predicate"=function(ctx) {variant.reference(ctx)=="A"} ),
	list("desc"="any allele is 'A'","predicate"=function(ctx) {"A"  %in% variant.alleles(ctx)} ),
	list("desc"="any ALT allele is 'A'","predicate"=function(ctx) {"A"  %in% variant.alt.alleles(ctx)} ),
	list("desc"="No QUAL","predicate"=function(ctx) {!variant.has.qual(ctx)} ),
	list("desc"="variant has ID","predicate"=function(ctx) {variant.has.id(ctx)}),
	list("desc"="variant ID match 'rs1*' ","predicate"=function(ctx) {grepl("^rs1",variant.id(ctx))}),
	list("desc"="variant has INFO/AF_NFE","predicate"=function(ctx) {variant.has.attribute(ctx,"AF_NFE")}),
	list("desc"="variant has INFO/AF_NFE > 1E-5","predicate"=function(ctx) {variant.has.attribute(ctx,"AF_NFE") && length(which(variant.float.attribute(ctx,"AF_NFE") > 1E-5))>0}),
	list("desc"="Missense in PLEKHN1 (VEP)","predicate"=function(ctx) {
		# NO VEP annotation ?
		if(!variant.has.attribute(ctx,"CSQ")) return(FALSE);
		# get VEP annotation
		predictions <- variant.vep(ctx)
		# In SCN5A
		predictions <- predictions[which(predictions$SYMBOL=="PLEKHN1"),]
		# Consequence must contain missense
		predictions <- predictions[grep("missense_variant",predictions$Consequence),]
		nrow(predictions)>0
		})
	)

# count the variant for each filter
for(flt in filters) {
	print(paste(basename(filename)," filter:",flt[["desc"]]," count:",count.variants(filename,flt[["predicate"]]),"\n"))
	}

	

Output:

[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: accept all  count: 50 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: accept none  count: 0 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: CHROM is '1'  count: 50 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: POS is even  count: 24 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: PASS filter  count: 48 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: count(FILTER)>1  count: 2 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: FILTER contains SEGDUP  count: 1 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: SNP  count: 47 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: POS!=END  count: 3 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: not diallelic  count: 8 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: REF is 'A'  count: 6 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: any allele is 'A'  count: 27 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: any ALT allele is 'A'  count: 21 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: No QUAL  count: 1 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: variant has ID  count: 34 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: variant ID match 'rs1*'   count: 2 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: variant has INFO/AF_NFE  count: 50 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: variant has INFO/AF_NFE > 1E-5  count: 14 \n"
[1] "gnomad.exomes.r2.0.1.sites.bcf  filter: Missense in PLEKHN1 (VEP)  count: 13 \n"

Print a VEP table for a Variant

Code:

# load rbcf
library(rbcf)
# A vcf
filename <- "./data/gnomad.exomes.r2.0.1.sites.bcf"
# we don't need the index for this file
fp <- bcf.open(filename,FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# current variant
vc <- NULL
while(!is.null(vc<-bcf.next(fp))) {
	#find the first variant having an INFO/CSQ attribute
	if(variant.has.attribute(vc,"CSQ")) break;
	}

if(!is.null(vc)) {
	# get the VEP table for the variant
	predictions<-variant.vep(vc)
	}

# dispose the vcf reader
bcf.close(fp)
# show
predictions

Output:

[1] TRUE
   Allele             Consequence   IMPACT   SYMBOL            Gene
1       C downstream_gene_variant MODIFIER   KLHL17 ENSG00000187961
2       A downstream_gene_variant MODIFIER   KLHL17 ENSG00000187961
3       C downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
4       A downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
5       C          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
6       A          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
7       C          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
8       A          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
9       C          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
10      A          intron_variant MODIFIER  PLEKHN1 ENSG00000187583
11      C downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
12      A downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
13      C downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
14      A downstream_gene_variant MODIFIER C1orf170 ENSG00000187642
15      C   upstream_gene_variant MODIFIER  PLEKHN1 ENSG00000187583
16      A   upstream_gene_variant MODIFIER  PLEKHN1 ENSG00000187583
17      C   upstream_gene_variant MODIFIER  PLEKHN1 ENSG00000187583
18      A   upstream_gene_variant MODIFIER  PLEKHN1 ENSG00000187583
   Feature_type         Feature         BIOTYPE EXON INTRON
1    Transcript ENST00000338591  protein_coding            
2    Transcript ENST00000338591  protein_coding            
3    Transcript ENST00000341290  protein_coding            
4    Transcript ENST00000341290  protein_coding            
5    Transcript ENST00000379407  protein_coding        2/14
6    Transcript ENST00000379407  protein_coding        2/14
7    Transcript ENST00000379409  protein_coding        2/14
8    Transcript ENST00000379409  protein_coding        2/14
9    Transcript ENST00000379410  protein_coding        2/15
10   Transcript ENST00000379410  protein_coding        2/15
11   Transcript ENST00000433179  protein_coding            
12   Transcript ENST00000433179  protein_coding            
13   Transcript ENST00000479361 retained_intron            
14   Transcript ENST00000479361 retained_intron            
15   Transcript ENST00000480267 retained_intron            
16   Transcript ENST00000480267 retained_intron            
17   Transcript ENST00000491024  protein_coding            
18   Transcript ENST00000491024  protein_coding            
                           HGVSc HGVSp cDNA_position CDS_position
1                                                                
2                                                                
3                                                                
4                                                                
5  ENST00000379407.3:c.184-51G>C                                 
6  ENST00000379407.3:c.184-51G>A                                 
7  ENST00000379409.2:c.184-51G>C                                 
8  ENST00000379409.2:c.184-51G>A                                 
9  ENST00000379410.3:c.184-51G>C                                 
10 ENST00000379410.3:c.184-51G>A                                 
11                                                               
12                                                               
13                                                               
14                                                               
15                                                               
16                                                               
17                                                               
18                                                               
   Protein_position Amino_acids Codons Existing_variation ALLELE_NUM DISTANCE
1                                             rs540662886          1     4511
2                                             rs540662886          2     4511
3                                             rs540662886          1     4978
4                                             rs540662886          2     4978
5                                             rs540662886          1         
6                                             rs540662886          2         
7                                             rs540662886          1         
8                                             rs540662886          2         
9                                             rs540662886          1         
10                                            rs540662886          2         
11                                            rs540662886          1     4973
12                                            rs540662886          2     4973
13                                            rs540662886          1     4979
14                                            rs540662886          2     4979
15                                            rs540662886          1      649
16                                            rs540662886          2      649
17                                            rs540662886          1     3286
18                                            rs540662886          2     3286
   STRAND        FLAGS VARIANT_CLASS MINIMISED SYMBOL_SOURCE HGNC_ID CANONICAL
1       1                        SNV                    HGNC   24023       YES
2       1                        SNV                    HGNC   24023       YES
3      -1                        SNV                    HGNC   28208          
4      -1                        SNV                    HGNC   28208          
5       1                        SNV                    HGNC   25284          
6       1                        SNV                    HGNC   25284          
7       1                        SNV                    HGNC   25284          
8       1                        SNV                    HGNC   25284          
9       1                        SNV                    HGNC   25284       YES
10      1                        SNV                    HGNC   25284       YES
11     -1                        SNV                    HGNC   28208       YES
12     -1                        SNV                    HGNC   28208       YES
13     -1                        SNV                    HGNC   28208          
14     -1                        SNV                    HGNC   28208          
15      1                        SNV                    HGNC   25284          
16      1                        SNV                    HGNC   25284          
17      1 cds_start_NF           SNV                    HGNC   25284          
18      1 cds_start_NF           SNV                    HGNC   25284          
   TSL APPRIS        CCDS            ENSP SWISSPROT        TREMBL       UNIPARC
1             CCDS30550.1 ENSP00000343930    Q6TDP4 Q0VGE6&B3KXL7 UPI00001DFBF0
2             CCDS30550.1 ENSP00000343930    Q6TDP4 Q0VGE6&B3KXL7 UPI00001DFBF0
3                         ENSP00000343864                         UPI000022DAF4
4                         ENSP00000343864                         UPI000022DAF4
5             CCDS53256.1 ENSP00000368717    Q494U1        J3KSM5 UPI00005764FF
6             CCDS53256.1 ENSP00000368717    Q494U1        J3KSM5 UPI00005764FF
7                         ENSP00000368719    Q494U1        J3KSM5 UPI0000D61E06
8                         ENSP00000368719    Q494U1        J3KSM5 UPI0000D61E06
9                 CCDS4.1 ENSP00000368720    Q494U1        J3KSM5 UPI00001416D8
10                CCDS4.1 ENSP00000368720    Q494U1        J3KSM5 UPI00001416D8
11                        ENSP00000414022    Q5SV97               UPI0000418FB0
12                        ENSP00000414022    Q5SV97               UPI0000418FB0
13                                                                             
14                                                                             
15                                                                             
16                                                                             
17                        ENSP00000462558                  J3KSM5 UPI000268AE1F
18                        ENSP00000462558                  J3KSM5 UPI000268AE1F
   GENE_PHENO SIFT PolyPhen DOMAINS HGVS_OFFSET     GMAF AFR_MAF AMR_MAF
1                                               C:0.0008     C:0     C:0
2                                               C:0.0008     C:0     C:0
3                                               C:0.0008     C:0     C:0
4                                               C:0.0008     C:0     C:0
5                                               C:0.0008     C:0     C:0
6                                               C:0.0008     C:0     C:0
7                                               C:0.0008     C:0     C:0
8                                               C:0.0008     C:0     C:0
9                                               C:0.0008     C:0     C:0
10                                              C:0.0008     C:0     C:0
11                                              C:0.0008     C:0     C:0
12                                              C:0.0008     C:0     C:0
13                                              C:0.0008     C:0     C:0
14                                              C:0.0008     C:0     C:0
15                                              C:0.0008     C:0     C:0
16                                              C:0.0008     C:0     C:0
17                                              C:0.0008     C:0     C:0
18                                              C:0.0008     C:0     C:0
   EAS_MAF EUR_MAF SAS_MAF AA_MAF EA_MAF ExAC_MAF ExAC_Adj_MAF ExAC_AFR_MAF
1      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
2      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
3      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
4      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
5      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
6      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
7      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
8      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
9      C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
10     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
11     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
12     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
13     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
14     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
15     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
16     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
17     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
18     C:0 C:0.004     C:0    C:0                          C:0  C:2.146e-04
   ExAC_AMR_MAF ExAC_EAS_MAF ExAC_FIN_MAF ExAC_NFE_MAF ExAC_OTH_MAF
1           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
2           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
3           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
4           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
5           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
6           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
7           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
8           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
9           C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
10          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
11          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
12          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
13          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
14          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
15          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
16          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
17          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
18          C:0  C:0.0002281   C:0.002986          C:0  C:1.606e-05
   ExAC_SAS_MAF CLIN_SIG SOMATIC PHENO PUBMED MOTIF_NAME MOTIF_POS HIGH_INF_POS
1           C:0                                                                
2           C:0                                                                
3           C:0                                                                
4           C:0                                                                
5           C:0                                                                
6           C:0                                                                
7           C:0                                                                
8           C:0                                                                
9           C:0                                                                
10          C:0                                                                
11          C:0                                                                
12          C:0                                                                
13          C:0                                                                
14          C:0                                                                
15          C:0                                                                
16          C:0                                                                
17          C:0                                                                
18          C:0                                                                
   MOTIF_SCORE_CHANGE LoF LoF_filter LoF_flags LoF_info"
1                                                       
2                                                       
3                                                       
4                                                       
5                                                       
6                                                       
7                                                       
8                                                       
9                                                       
10                                                      
11                                                      
12                                                      
13                                                      
14                                                      
15                                                      
16                                                      
17                                                      
18                                                      

Print a SNPEFF table for a Variant

Code:

# load rbcf
library(rbcf)
# A vcf
filename <- "./data/rotavirus_rf.ann.vcf.gz"
# we don't need the index for this file
fp <- bcf.open(filename,FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# current variant
vc <- NULL
while(!is.null(vc<-bcf.next(fp))) {
	#find the first variant having an INFO/ANN attribute
	if(variant.has.attribute(vc,"ANN")) break;
	}
if(!is.null(vc)) {
	# get SNPEFF table
	predictions<-variant.snpeff(vc)
	}
# dispose the vcf reader
bcf.close(fp)
# show
predictions

Output:

[1] TRUE
  Allele       Annotation Annotation_Impact    Gene_Name      Gene_ID
1      C missense_variant          MODERATE Gene_18_3284 Gene_18_3284
  Feature_Type Feature_ID Transcript_BioType Rank   HGVS.c      HGVS.p
1   transcript AAA47319.1     protein_coding  1/1 c.952A>C p.Lys318Gln
  cDNA.pos / cDNA.length CDS.pos / CDS.length AA.pos / AA.length Distance
1               952/3267             952/3267           318/1088         
  ERRORS / WARNINGS / INFO'"
1                           

Query the indexed vcf using intervals

Code:

# load rbcf
library(rbcf)

# create a function counting variants in a VCF, in some intervals
count.variants<-function(filename,intervals) {
	# open the indexed VCF
	fp <- bcf.open(filename)
	# error on opening
	if(is.null(fp)) return(-1)
	# loop over the intervals
	for(interval in intervals) {
		# try query the interval
		if(bcf.query(fp,interval)) {
			# number of variants
			n<-0
			# loop while we can read a variant
			while(!is.null(vc<-bcf.next(fp))) {
				# increment the count
				n<-n+1
				}
			print(paste("Number of variants in ",basename(filename),"/'",interval,"' :",n,sep=""))
			}
		# query failed
		else {
			print(paste("Cannot query ",basename(filename),"/'",interval,"'",sep=""))
			}
		}
	# dispose the vcf reader
	bcf.close(fp)
}

some_intervals <-c("","RF03","RF03:2000-3000","1:1-10000000","chr1")
count.variants("./data/rotavirus_rf.02.vcf.gz",some_intervals)
count.variants("./data/1000G.ALL.2of4intersection.20100804.genotypes.bcf",some_intervals)

# another way to query is set collect=TRUE to return a vector of variant
fp <- bcf.open("./data/rotavirus_rf.02.vcf.gz")
if(!is.null(fp)) {
	print(paste("Number of variants using collect:",length(bcf.query(fp,"RF03",collect=TRUE))))
	bcf.close(fp)
	}

Output:

[1] "Cannot query rotavirus_rf.02.vcf.gz/''"
[1] "Number of variants in rotavirus_rf.02.vcf.gz/'RF03' :8"
[1] "Number of variants in rotavirus_rf.02.vcf.gz/'RF03:2000-3000' :4"
[1] "Cannot query rotavirus_rf.02.vcf.gz/'1:1-10000000'"
[1] "Cannot query rotavirus_rf.02.vcf.gz/'chr1'"
[1] TRUE
[1] "Cannot query 1000G.ALL.2of4intersection.20100804.genotypes.bcf/''"
[1] "Cannot query 1000G.ALL.2of4intersection.20100804.genotypes.bcf/'RF03'"
[1] "Cannot query 1000G.ALL.2of4intersection.20100804.genotypes.bcf/'RF03:2000-3000'"
[1] "Number of variants in 1000G.ALL.2of4intersection.20100804.genotypes.bcf/'1:1-10000000' :11"
[1] "Cannot query 1000G.ALL.2of4intersection.20100804.genotypes.bcf/'chr1'"
[1] TRUE
[1] "Number of variants using collect: 8"
[1] TRUE

Attribute in INFO

Code:

# load rbcf
library(rbcf)

# find given variant
find.variant<-function(fp,contig,pos) {
	if(!bcf.query(fp,paste(contig,":",pos,"-",pos,sep=""))) return(NULL)
	# loop while we can read a variant
	while(!is.null(vc<-bcf.next(fp))) {
		return(vc)
	}
	return(NULL)
}
filename<-"./data/gnomad.exomes.r2.0.1.sites.bcf"
# open the VCF with index
fp <- bcf.open(filename)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)

ctx <-find.variant(fp,"1",905608)
stopifnot(variant.has.attribute(ctx,"CSQ"))
print(paste("CSQ(no split) ",variant.string.attribute(ctx,"CSQ",split=FALSE)))
print(paste("CSQ(split) ",variant.string.attribute(ctx,"CSQ")))
stopifnot(variant.has.attribute(ctx,"AN_POPMAX"))
print(paste("AN_POPMAX:",variant.int.attribute(ctx,"AN_POPMAX")))
stopifnot(variant.has.attribute(ctx,"AF_POPMAX"))
print(paste("AF_POPMAX:",variant.float.attribute(ctx,"AF_POPMAX")))
print(paste("flag:VQSR_NEGATIVE_TRAIN_SITE:",variant.flag.attribute(ctx,"VQSR_NEGATIVE_TRAIN_SITE")))
# dispose the vcf reader
bcf.close(fp)

Output:

[1] "CSQ(no split)  T|downstream_gene_variant|MODIFIER|KLHL17|ENSG00000187961|Transcript|ENST00(...)
 [1] "CSQ(split)  T|downstream_gene_variant|MODIFIER|KLHL17|ENSG00000187961|Transcript|ENST0000(...)
 [2] "CSQ(split)  A|downstream_gene_variant|MODIFIER|KLHL17|ENSG00000187961|Transcript|ENST0000(...)
 [3] "CSQ(split)  T|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
 [4] "CSQ(split)  A|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
 [5] "CSQ(split)  T|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379407|(...)
 [6] "CSQ(split)  A|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379407|(...)
 [7] "CSQ(split)  T|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379409|(...)
 [8] "CSQ(split)  A|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379409|(...)
 [9] "CSQ(split)  T|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379410|(...)
[10] "CSQ(split)  A|intron_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000379410|(...)
[11] "CSQ(split)  T|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
[12] "CSQ(split)  A|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
[13] "CSQ(split)  T|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
[14] "CSQ(split)  A|downstream_gene_variant|MODIFIER|C1orf170|ENSG00000187642|Transcript|ENST00(...)
[15] "CSQ(split)  T|upstream_gene_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000(...)
[16] "CSQ(split)  A|upstream_gene_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000(...)
[17] "CSQ(split)  T|upstream_gene_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000(...)
[18] "CSQ(split)  A|upstream_gene_variant|MODIFIER|PLEKHN1|ENSG00000187583|Transcript|ENST00000(...)
[1] "AN_POPMAX: 106408" "AN_POPMAX: 106408"
[1] "AF_POPMAX: 1.87955993169453e-05" "AF_POPMAX: 9.39778965403093e-06"
[1] "flag:VQSR_NEGATIVE_TRAIN_SITE: FALSE"
[1] TRUE

Working with Genotypes

Code:

# load rbcf
library(rbcf)

# find given variant
find.variant<-function(fp,contig,pos) {
	if(!bcf.query(fp,paste(contig,":",pos,"-",pos,sep=""))) return(NULL)
	# loop while we can read a variant
	while(!is.null(vc<-bcf.next(fp))) {
		return(vc)
	}
	return(NULL)
}
filename<-"./data/1000G.ALL.2of4intersection.20100804.genotypes.bcf"
# open the VCF with index
fp <- bcf.open(filename)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# find a variant
ctx <-find.variant(fp,"1",10583)
print(paste("Number of genotypes ",variant.nsamples(ctx)))
# get 10-th genotype
gt<-variant.genotype(ctx,10)
print(paste("sample ",genotype.sample(gt)))
# get genotype by name
gt<-variant.genotype(ctx,"NA18997")
print(paste("sample ",genotype.sample(gt)))
print(paste("alleles ",genotype.alleles.idx0(gt)))
print(paste("genotype ploidy ? ",genotype.ploidy(gt)))
print(paste("genotype is hom ref ? ",genotype.homref(gt)))
print(paste("genotype is het ? ",genotype.het(gt)))
print(paste("genotype is het-non-ref ? ",genotype.hetnonref(gt)))
print(paste("genotype is phased ? ",genotype.phased(gt)))
print(paste("genotype is no call ? ",genotype.nocall(gt)))
print(paste("genotype FORMAT/OG ? ",genotype.string.attribute(gt,"OG")))
print(paste("genotype FORMAT/GQ ? ",genotype.int.attribute(gt,"GQ")))# hum spec says gt should be integer
print(paste("genotype has GQ ? ",genotype.has.gq(gt)))
print(paste("genotype GQ ",genotype.gq(gt)))
print(paste("genotype has DP ? ",genotype.has.dp(gt)))
print(paste("genotype DP ",genotype.int.attribute(gt,"DP")))
print(paste("genotype DP ",genotype.dp(gt)))
print(paste("genotype has PL ? ",genotype.has.pl(gt)))
print(paste("genotype PL ",genotype.pl(gt)))
print(paste("genotype has AD ? ",genotype.has.ad(gt)))
print(paste("genotype AD ",genotype.ad(gt)))

# dispose the vcf reader
bcf.close(fp)

Output:

[1] "Number of genotypes  629"
[1] "sample  HG00120"
[1] "sample  NA18997"
[1] "alleles  0" "alleles  1"
[1] "genotype ploidy ?  2"
[1] "genotype is hom ref ?  FALSE"
[1] "genotype is het ?  TRUE"
[1] "genotype is het-non-ref ?  FALSE"
[1] "genotype is phased ?  TRUE"
[1] "genotype is no call ?  FALSE"
[1] "genotype FORMAT/OG ?  1/1"
[1] "genotype FORMAT/GQ ?  "
[1] "genotype has GQ ?  FALSE"
[1] "genotype GQ  -1"
[1] "genotype has DP ?  TRUE"
[1] "genotype DP  1"
[1] "genotype DP  1"
[1] "genotype has PL ?  FALSE"
[1] "genotype PL  "
[1] "genotype has AD ?  TRUE"
[1] "genotype AD  4" "genotype AD  1"
[1] TRUE

Working with vectorized Genotypes

Code:

# load rbcf
library(rbcf)

# find given variant
find.variant<-function(fp,contig,pos) {
	if(!bcf.query(fp,paste(contig,":",pos,"-",pos,sep=""))) return(NULL)
	# loop while we can read a variant
	while(!is.null(vc<-bcf.next(fp))) {
		return(vc)
	}
	return(NULL)
}
filename<-"./data/1000G.ALL.2of4intersection.20100804.genotypes.bcf"
# open the VCF with index
fp <- bcf.open(filename)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)
# find a variant
ctx <-find.variant(fp,"1",10583)
print(paste("Number of genotypes ",variant.nsamples(ctx)))

# Retrieve the DP for all genotypes (length of vector equals to number of samples)
dp <- variant.genotypes.int.attribute(ctx, "DP")
stopifnot(length(dp) == variant.nsamples(ctx))
stopifnot(is.integer(dp))
cat("DP: ", paste(dp, collapse = ", "), "\n")

# Retrieve the GQ for all genotypes (length of vector equals to number of samples)
gq <- variant.genotypes.float.attribute(ctx, "GQ")
stopifnot(length(gq) == variant.nsamples(ctx))
stopifnot(is.numeric(gq))
cat("GQ: ", paste(gq, collapse = ", "), "\n")

# Retrieve the AD for all genotypes (length of vector equals to 2x number of samples)
#  The first two number contain the AD for REF and ALT for the first sample respectively.
ad <- variant.genotypes.int.attribute(ctx, "AD")
stopifnot(length(ad) == 2*variant.nsamples(ctx))
stopifnot(is.integer(ad))
cat("AD: ", paste(ad, collapse = ", "), "\n")

# Helper function to get all the GT indizes
gt <- variant.genotypes.allele.idx0(ctx)
stopifnot(length(gt) == 2*variant.nsamples(ctx))
stopifnot(is.integer(gt))
cat("GT - Integers: ", paste(gt, collapse = ", "), "\n")

# Helper function to get all the GT allele-counts
gt <- variant.genotypes.allele.counts(ctx, 0)
stopifnot(length(gt) == variant.nsamples(ctx))
stopifnot(is.integer(gt))
cat("GT - Allele Counts (Reference): ", paste(gt, collapse = ", "), "\n")

gtc <- variant.genotypes.allele.counts(ctx, 1)
stopifnot(length(gtc) == variant.nsamples(ctx))
stopifnot(is.integer(gtc))
cat("GT - Allele Counts (Alternative): ", paste(gtc, collapse = ", "), "\n")

# Helper function to get all the GT strings
gt <- variant.genotypes.allele.strings(ctx)
stopifnot(length(gt) == variant.nsamples(ctx))
stopifnot(is.character(gt))
cat("GT - Strings: ", paste(gt, collapse = ", "), "\n")

# dispose the vcf reader
bcf.close(fp)

Output:

[1] "Number of genotypes  629"
DP:  NA, NA, NA, NA, NA, NA, 2, NA, 1, 5, NA, NA, 1, NA, NA, 3, NA, NA, NA, 4, 1, 1, 1, 1, NA, (...)
GQ:  3.27999997138977, 3.27999997138977, 3.27999997138977, 3.27999997138977, 3.27999997138977, (...)
AD:  NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 2, 0, NA, NA, 5, 1, 4, 1, NA, NA, NA, NA, (...)
GT - Integers:  0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0(...)
GT - Allele Counts (Reference):  2, 2, 2, 2, 2, 2, 2, 2, 2, 1, 2, 2, 2, 2, 2, 2, 2, 2, 2, 2, 1,(...)
GT - Allele Counts (Alternative):  0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, (...)
GT - Strings:  0|0, 0|0, 0|0, 0|0, 0|0, 0|0, 0|0, 0|0, 0|0, 0|1, 0|0, 0|0, 0|0, 0|0, 0|0, 0|0, (...)
[1] TRUE

Writing variants to a new VCF/BCF file

Code:

# load rbcf
library(rbcf)
# vcf input filename
filenamein = "./data/rotavirus_rf.01.vcf"
# output vcf filename. "-" is standard output
filenameout =  "-"

fp <- bcf.open(filenamein,FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)

# create a new VCF writer using the header from 'fp'
out <- bcf.new.writer(fp,filenameout)
# error on opening (exit 0 for tests)
if(is.null(out)) quit(save="no",status=0,runLast=FALSE)

# loop while we can read a variant
while(!is.null(vc<-bcf.next(fp))) {
	# only write POS%10==0
	if(variant.pos(vc)%%10==0) { 
		# write variant
		bcf.write.variant(out,vc);
		}
	}
# dispose the vcf reader
bcf.close(fp)
# dispose the vcf rwriter
bcf.close(out);

Output:

[1] TRUE
##fileformat=VCFv4.2
##FILTER=<ID=PASS,Description="All filters passed">
##samtoolsVersion=1.3.1+htslib-1.3.1
##samtoolsCommand=samtools mpileup -Ou -f rotavirus_rf.fa S1.bam S2.bam S3.bam S4.bam S5.bam
##reference=file://rotavirus_rf.fa
##contig=<ID=RF01,length=3302>
##contig=<ID=RF02,length=2687>
##contig=<ID=RF03,length=2592>
##contig=<ID=RF04,length=2362>
##contig=<ID=RF05,length=1579>
##contig=<ID=RF06,length=1356>
##contig=<ID=RF07,length=1074>
##contig=<ID=RF08,length=1059>
##contig=<ID=RF09,length=1062>
##contig=<ID=RF10,length=751>
##contig=<ID=RF11,length=666>
##ALT=<ID=*,Description="Represents allele(s) other than observed.">
##INFO=<ID=INDEL,Number=0,Type=Flag,Description="Indicates that the variant is an INDEL.">
##INFO=<ID=IDV,Number=1,Type=Integer,Description="Maximum number of reads supporting an indel">
##INFO=<ID=IMF,Number=1,Type=Float,Description="Maximum fraction of reads supporting an indel">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Raw read depth">
##INFO=<ID=VDB,Number=1,Type=Float,Description="Variant Distance Bias for filtering splice-site(...)
##INFO=<ID=RPB,Number=1,Type=Float,Description="Mann-Whitney U test of Read Position Bias (bigg(...)
##INFO=<ID=MQB,Number=1,Type=Float,Description="Mann-Whitney U test of Mapping Quality Bias (bi(...)
##INFO=<ID=BQB,Number=1,Type=Float,Description="Mann-Whitney U test of Base Quality Bias (bigge(...)
##INFO=<ID=MQSB,Number=1,Type=Float,Description="Mann-Whitney U test of Mapping Quality vs Stra(...)
##INFO=<ID=SGB,Number=1,Type=Float,Description="Segregation based metric.">
##INFO=<ID=MQ0F,Number=1,Type=Float,Description="Fraction of MQ0 reads (smaller is better)">
##FORMAT=<ID=PL,Number=G,Type=Integer,Description="List of Phred-scaled genotype likelihoods">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##INFO=<ID=ICB,Number=1,Type=Float,Description="Inbreeding Coefficient Binomial test (bigger is(...)
##INFO=<ID=HOB,Number=1,Type=Float,Description="Bias in the number of HOMs number (smaller is b(...)
##INFO=<ID=AC,Number=A,Type=Integer,Description="Allele count in genotypes for each ALT allele,(...)
##INFO=<ID=AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes">
##INFO=<ID=DP4,Number=4,Type=Integer,Description="Number of high-quality ref-forward , ref-reve(...)
##INFO=<ID=MQ,Number=1,Type=Integer,Description="Average mapping quality">
##bcftools_callVersion=1.3-10-g820e1d6+htslib-1.2.1-267-g87141ea
##bcftools_callCommand=call -vm -Oz -o rotavirus_rf.vcf.gz -
##bcftools_viewVersion=1.10-6-g2782d9f+htslib-1.2.1-1336-g7c16b56-dirty
##bcftools_viewCommand=view /home/lindenb/src/jvarkit/src/test/resources/rotavirus_rf.vcf.gz; D(...)
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO	FORMAT	S1	S2	S3	S4	S5
RF01	970	.	A	C	48.6696	.	DP=36;VDB=0.693968;SGB=10.3229;RPB=0.658863;MQB=1;MQSB=1;BQB=0.572843;(...)
RF03	2150	.	T	A	6.90687	.	DP=37;VDB=0.557348;SGB=-1.00336;RPB=0.579851;MQB=1;MQSB=1;BQB=1;MQ0F=(...)
RF04	1900	.	A	C	36.8224	.	DP=39;VDB=0.706942;SGB=7.10992;RPB=0.81363;MQB=1;MQSB=1;BQB=1;MQ0F=0;(...)
RF04	1920	.	A	T	42.014	.	DP=39;VDB=0.966939;SGB=0.816387;RPB=0.864752;MQB=1;MQSB=1;BQB=0.864752(...)

Setting FORMAT in variant genotypes

Code:

# load rbcf
library(rbcf)
# vcf input filename
filenamein = "./data/1000G.ALL.2of4intersection.20100804.genotypes.bcf"
# output vcf filename. "-" is standard output
filenameout =  "-"

fp <- bcf.open(filenamein,FALSE)
# error on opening (exit 0 for tests)
if(is.null(fp)) quit(save="no",status=0,runLast=FALSE)

# create a new VCF writer using the header from 'fp'
out <- bcf.new.writer(fp,filenameout)
# error on opening (exit 0 for tests)
if(is.null(out)) quit(save="no",status=0,runLast=FALSE)

n_samples <- bcf.nsamples(fp)

# loop while we can read a variant
while(!is.null(vc<-bcf.next(fp))) {
  # Setting of INT attributes
  old_dp <- variant.genotypes.int.attribute(vc, "DP")
  new_dp <- rnbinom(n = n_samples, size = 5, prob = 0.25)
  variant.genotypes.set.int.attribute(vc, "DP", new_dp)
  stopifnot( all(  new_dp == variant.genotypes.int.attribute(vc, "DP") ))

  old_gq <- variant.genotypes.float.attribute(vc, "GQ")
  new_gq <- rnorm(n = n_samples)
  variant.genotypes.set.float.attribute(vc, "GQ", new_gq)
  #stopifnot( all(  new_gq == variant.genotypes.float.attribute(vc, "GQ") ))
  
  
  # Updating GT with random allele combinations
  alleles <- c(".", as.character(0:variant.nalleles(vc)))
  all_potential_genotypes = c(".",
    apply(as.matrix(expand.grid(alleles, alleles)), 1, paste, collapse = "/"),
    apply(as.matrix(expand.grid(0:variant.nalleles(vc), 0:variant.nalleles(vc))), 1, paste, collapse = "|")
  )
  
  new_gt <- sample(x = all_potential_genotypes, size = n_samples, replace = TRUE)
  variant.genotypes.set.allele.strings(vc, new_gt)
  new_gt <- sub("-", ".", new_gt)
  subset(data.frame( Expected = new_gt, Seen = variant.genotypes.allele.strings(vc)), Expected != Seen)
  
  stopifnot(all(  new_gt == variant.genotypes.allele.strings(vc) ))
  
  bcf.write.variant(out, vc)
}
# dispose the vcf reader
bcf.close(fp)
# dispose the vcf rwriter
bcf.close(out)

Output:

##fileformat=VCFv4.0
##FILTER=<ID=PASS,Description="All filters passed">
##filedat=20101112
##datarelease=20100804
##samples=629
##contig=<ID=1,length=249250621>
##description="Where BI calls are present, genotypes and alleles are from BI.  In there absence(...)
##FORMAT=<ID=AD,Number=A,Type=Integer,Description="Allelic depths for the ref and alt alleles i(...)
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth (only filtered reads used for cal(...)
##FORMAT=<ID=GL,Number=G,Type=Float,Description="Log-scaled likelihoods for AA,AB,BB genotypes (...)
##FORMAT=<ID=GQ,Number=1,Type=Float,Description="Genotype Quality">
##FORMAT=<ID=GT,Number=A,Type=String,Description="Genotype">
##FORMAT=<ID=GD,Number=1,Type=Float,Description="Genotype dosage.  Expected count of non-ref al(...)
##FORMAT=<ID=OG,Number=1,Type=String,Description="Original Genotype input to Beagle">
##INFO=<ID=AF,Number=.,Type=Float,Description="Allele Frequency, for each ALT allele, in the sa(...)
##INFO=<ID=DP,Number=1,Type=Integer,Description="Total Depth">
##INFO=<ID=CB,Number=.,Type=String,Description="List of centres that called, UM (University of (...)
##INFO=<ID=EUR_R2,Number=1,Type=Float,Description="R2 From Beagle based on European Samples">
##INFO=<ID=AFR_R2,Number=1,Type=Float,Description="R2 From Beagle based on AFRICAN Samples">
##INFO=<ID=ASN_R2,Number=1,Type=Float,Description="R2 From Beagle based on Asian Samples">
##bcftools_viewVersion=1.9-321-g5774f32+htslib-1.10.2-22-gbfc9f0d
##bcftools_viewCommand=view -O b -o 1000G.ALL.2of4intersection.20100804.genotypes.bcf 1000G.ALL(...)
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO	FORMAT	HG00098	HG00100	HG00106	HG00112	HG00114	HG00116	H(...)
1	10583	rs58108140	G	A	.	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1	11508	.	A	G	.	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1	11565	.	G	T	.	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1	15274	.	A	T	.	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1	15820	.	G	T	.	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1	16378	.	T	C	.	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1	28376	.	G	A	.	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