Merges one or more HaplotypeCaller GVCF files into a single GVCF with appropriate annotations
Category Short Variant Discovery
Overview
Combine per-sample gVCF files produced by HaplotypeCaller into a multi-sample gVCF fileCombineGVCFs is meant to be used for merging of GVCFs that will eventually be input into GenotypeGVCFs. One could use this tool to genotype multiple individual GVCFs instead of GenomicsDBImport; one would first use CombineGVCFs to combine them into a single GVCF and pass the results into GenotypeGVCFs. The main advantage of using CombineGVCFs over GenomicsDBImport is the ability to combine multiple intervals at once without building a GenomicsDB. CombineGVCFs is slower than GenomicsDBImport though, so it is recommended CombineGVCFs only be used when there are few samples to merge.
Input
Two or more HaplotypeCaller GVCFs to combine.
Output
A combined multi-sample gVCF.
Usage example
gatk CombineGVCFs \ -R reference.fasta \ --variant sample1.g.vcf.gz \ --variant sample2.g.vcf.gz \ -O cohort.g.vcf.gz
Caveats
Only GVCF files produced by HaplotypeCaller (or CombineGVCFs) can be used as input for this tool. Some other programs produce files that they call GVCFs but those lack some important information (accurate genotype likelihoods for every position) that GenotypeGVCFs requires for its operation.
If the GVCF files contain allele specific annotations, add `-G Standard -G AS_Standard` to the command line.
Users generating large callsets (1000+ samples) may prefer GenomicsDBImport, which uses Intel's GenomicsDB and is capable of scaling to much larger sample sizes than CombineGVCFs. This tool provides a pure java reference implementation of the combine operation which is available on all architectures.
CombineGVCFs specific arguments
This table summarizes the command-line arguments that are specific to this tool. For more details on each argument, see the list further down below the table or click on an argument name to jump directly to that entry in the list.
Argument name(s) | Default value | Summary | |
---|---|---|---|
Required Arguments | |||
--output -O |
null | The combined GVCF output file | |
--reference -R |
null | Reference sequence file | |
--variant -V |
[] | One or more VCF files containing variants | |
Optional Tool Arguments | |||
--annotation -A |
[] | One or more specific annotations to add to variant calls | |
--annotation-group -G |
[] | One or more groups of annotations to apply to variant calls | |
--annotations-to-exclude -AX |
[] | One or more specific annotations to exclude from variant calls | |
--arguments_file |
[] | read one or more arguments files and add them to the command line | |
--break-bands-at-multiples-of |
0 | If > 0, reference bands will be broken up at genomic positions that are multiples of this number | |
--cloud-index-prefetch-buffer -CIPB |
-1 | Size of the cloud-only prefetch buffer (in MB; 0 to disable). Defaults to cloudPrefetchBuffer if unset. | |
--cloud-prefetch-buffer -CPB |
40 | Size of the cloud-only prefetch buffer (in MB; 0 to disable). | |
--convert-to-base-pair-resolution |
false | If specified, convert banded gVCFs to all-sites gVCFs | |
--dbsnp -D |
null | dbSNP file | |
--disable-bam-index-caching -DBIC |
false | If true, don't cache bam indexes, this will reduce memory requirements but may harm performance if many intervals are specified. Caching is automatically disabled if there are no intervals specified. | |
--disable-sequence-dictionary-validation |
false | If specified, do not check the sequence dictionaries from our inputs for compatibility. Use at your own risk! | |
--founder-id |
[] | Samples representing the population "founders" | |
--gcs-max-retries -gcs-retries |
20 | If the GCS bucket channel errors out, how many times it will attempt to re-initiate the connection | |
--help -h |
false | display the help message | |
--interval-merging-rule -imr |
ALL | Interval merging rule for abutting intervals | |
--intervals -L |
[] | One or more genomic intervals over which to operate | |
--pedigree -ped |
null | Pedigree file for determining the population "founders" | |
--sites-only-vcf-output |
false | If true, don't emit genotype fields when writing vcf file output. | |
--version |
false | display the version number for this tool | |
Optional Common Arguments | |||
--add-output-sam-program-record |
true | If true, adds a PG tag to created SAM/BAM/CRAM files. | |
--add-output-vcf-command-line |
true | If true, adds a command line header line to created VCF files. | |
--create-output-bam-index -OBI |
true | If true, create a BAM/CRAM index when writing a coordinate-sorted BAM/CRAM file. | |
--create-output-bam-md5 -OBM |
false | If true, create a MD5 digest for any BAM/SAM/CRAM file created | |
--create-output-variant-index -OVI |
true | If true, create a VCF index when writing a coordinate-sorted VCF file. | |
--create-output-variant-md5 -OVM |
false | If true, create a a MD5 digest any VCF file created. | |
--disable-read-filter -DF |
[] | Read filters to be disabled before analysis | |
--disable-tool-default-read-filters |
false | Disable all tool default read filters (WARNING: many tools will not function correctly without their default read filters on) | |
--exclude-intervals -XL |
[] | One or more genomic intervals to exclude from processing | |
--gatk-config-file |
null | A configuration file to use with the GATK. | |
--input -I |
[] | BAM/SAM/CRAM file containing reads | |
--interval-exclusion-padding -ixp |
0 | Amount of padding (in bp) to add to each interval you are excluding. | |
--interval-padding -ip |
0 | Amount of padding (in bp) to add to each interval you are including. | |
--interval-set-rule -isr |
UNION | Set merging approach to use for combining interval inputs | |
--lenient -LE |
false | Lenient processing of VCF files | |
--QUIET |
false | Whether to suppress job-summary info on System.err. | |
--read-filter -RF |
[] | Read filters to be applied before analysis | |
--read-index |
[] | Indices to use for the read inputs. If specified, an index must be provided for every read input and in the same order as the read inputs. If this argument is not specified, the path to the index for each input will be inferred automatically. | |
--read-validation-stringency -VS |
SILENT | Validation stringency for all SAM/BAM/CRAM/SRA files read by this program. The default stringency value SILENT can improve performance when processing a BAM file in which variable-length data (read, qualities, tags) do not otherwise need to be decoded. | |
--seconds-between-progress-updates |
10.0 | Output traversal statistics every time this many seconds elapse | |
--sequence-dictionary |
null | Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file. | |
--TMP_DIR |
[] | Undocumented option | |
--use-jdk-deflater -jdk-deflater |
false | Whether to use the JdkDeflater (as opposed to IntelDeflater) | |
--use-jdk-inflater -jdk-inflater |
false | Whether to use the JdkInflater (as opposed to IntelInflater) | |
--verbosity |
INFO | Control verbosity of logging. | |
Advanced Arguments | |||
--disable-tool-default-annotations |
false | Disable all tool default annotations | |
--enable-all-annotations |
false | Use all possible annotations (not for the faint of heart) | |
--ignore-variants-starting-outside-interval |
false | Restrict variant output to sites that start within provided intervals (only applies when an interval is specified) | |
--showHidden |
false | display hidden arguments |
Argument details
Arguments in this list are specific to this tool. Keep in mind that other arguments are available that are shared with other tools (e.g. command-line GATK arguments); see Inherited arguments above.
--add-output-sam-program-record / -add-output-sam-program-record
If true, adds a PG tag to created SAM/BAM/CRAM files.
boolean true
--add-output-vcf-command-line / -add-output-vcf-command-line
If true, adds a command line header line to created VCF files.
boolean true
--annotation / -A
One or more specific annotations to add to variant calls
Which annotations to include in variant calls in the output. These supplement annotations provided by annotation groups.
List[String] []
--annotation-group / -G
One or more groups of annotations to apply to variant calls
Which groups of annotations to add to the output variant calls.
Any requirements that are not met (e.g. failing to provide a pedigree file for a pedigree-based annotation) may cause the run to fail.
List[String] []
--annotations-to-exclude / -AX
One or more specific annotations to exclude from variant calls
Which annotations to exclude from output in the variant calls. Note that this argument has higher priority than the
-A or -G arguments, so these annotations will be excluded even if they are explicitly included with the other
options.
List[String] []
--arguments_file / NA
read one or more arguments files and add them to the command line
List[File] []
--break-bands-at-multiples-of / NA
If > 0, reference bands will be broken up at genomic positions that are multiples of this number
To reduce file sizes our gVCFs group similar reference positions into bands. However, there are cases when users will want to know that no bands
span across a given genomic position (e.g. when scatter-gathering jobs across a compute farm). The option below enables users to break bands at
pre-defined positions. For example, a value of 10,000 would mean that we would ensure that no bands span across chr1:10000, chr1:20000, etc.
Note that the --convertToBasePairResolution argument is just a special case of this argument with a value of 1.
int 0 [ [ -∞ ∞ ] ]
--cloud-index-prefetch-buffer / -CIPB
Size of the cloud-only prefetch buffer (in MB; 0 to disable). Defaults to cloudPrefetchBuffer if unset.
int -1 [ [ -∞ ∞ ] ]
--cloud-prefetch-buffer / -CPB
Size of the cloud-only prefetch buffer (in MB; 0 to disable).
int 40 [ [ -∞ ∞ ] ]
--convert-to-base-pair-resolution / NA
If specified, convert banded gVCFs to all-sites gVCFs
boolean false
--create-output-bam-index / -OBI
If true, create a BAM/CRAM index when writing a coordinate-sorted BAM/CRAM file.
boolean true
--create-output-bam-md5 / -OBM
If true, create a MD5 digest for any BAM/SAM/CRAM file created
boolean false
--create-output-variant-index / -OVI
If true, create a VCF index when writing a coordinate-sorted VCF file.
boolean true
--create-output-variant-md5 / -OVM
If true, create a a MD5 digest any VCF file created.
boolean false
--dbsnp / -D
dbSNP file
A dbSNP VCF file.
FeatureInput[VariantContext] null
--disable-bam-index-caching / -DBIC
If true, don't cache bam indexes, this will reduce memory requirements but may harm performance if many intervals are specified. Caching is automatically disabled if there are no intervals specified.
boolean false
--disable-read-filter / -DF
Read filters to be disabled before analysis
List[String] []
--disable-sequence-dictionary-validation / -disable-sequence-dictionary-validation
If specified, do not check the sequence dictionaries from our inputs for compatibility. Use at your own risk!
boolean false
--disable-tool-default-annotations / -disable-tool-default-annotations
Disable all tool default annotations
Hook allowing for the user to remove default annotations from the tool
boolean false
--disable-tool-default-read-filters / -disable-tool-default-read-filters
Disable all tool default read filters (WARNING: many tools will not function correctly without their default read filters on)
boolean false
--enable-all-annotations / NA
Use all possible annotations (not for the faint of heart)
You can use the -AX argument in combination with this one to exclude specific annotations. Note that some
annotations may not be actually applied if they are not applicable to the data provided or if they are
unavailable to the tool (e.g. there are several annotations that are currently not hooked up to
HaplotypeCaller). At present no error or warning message will be provided, the annotation will simply be
skipped silently. You can check the output VCF header to see which annotations were activated and thus might be applied (although
this does not guarantee that the annotation was applied to all records in the VCF, since some annotations have
additional requirements, e.g. minimum number of samples or heterozygous sites only -- see the documentation
for individual annotations' requirements).
boolean false
--exclude-intervals / -XL
One or more genomic intervals to exclude from processing
Use this argument to exclude certain parts of the genome from the analysis (like -L, but the opposite).
This argument can be specified multiple times. You can use samtools-style intervals either explicitly on the
command line (e.g. -XL 1 or -XL 1:100-200) or by loading in a file containing a list of intervals
(e.g. -XL myFile.intervals).
List[String] []
--founder-id / -founder-id
Samples representing the population "founders"
List[String] []
--gatk-config-file / NA
A configuration file to use with the GATK.
String null
--gcs-max-retries / -gcs-retries
If the GCS bucket channel errors out, how many times it will attempt to re-initiate the connection
int 20 [ [ -∞ ∞ ] ]
--help / -h
display the help message
boolean false
--ignore-variants-starting-outside-interval / NA
Restrict variant output to sites that start within provided intervals (only applies when an interval is specified)
this option has no effect unless intervals are specified.
This exists to mimic GATK3 interval traversal patterns
boolean false
--input / -I
BAM/SAM/CRAM file containing reads
List[String] []
--interval-exclusion-padding / -ixp
Amount of padding (in bp) to add to each interval you are excluding.
Use this to add padding to the intervals specified using -XL. For example, '-XL 1:100' with a
padding value of 20 would turn into '-XL 1:80-120'. This is typically used to add padding around targets when
analyzing exomes.
int 0 [ [ -∞ ∞ ] ]
--interval-merging-rule / -imr
Interval merging rule for abutting intervals
By default, the program merges abutting intervals (i.e. intervals that are directly side-by-side but do not
actually overlap) into a single continuous interval. However you can change this behavior if you want them to be
treated as separate intervals instead.
The --interval-merging-rule argument is an enumerated type (IntervalMergingRule), which can have one of the following values:
- ALL
- OVERLAPPING_ONLY
IntervalMergingRule ALL
--interval-padding / -ip
Amount of padding (in bp) to add to each interval you are including.
Use this to add padding to the intervals specified using -L. For example, '-L 1:100' with a
padding value of 20 would turn into '-L 1:80-120'. This is typically used to add padding around targets when
analyzing exomes.
int 0 [ [ -∞ ∞ ] ]
--interval-set-rule / -isr
Set merging approach to use for combining interval inputs
By default, the program will take the UNION of all intervals specified using -L and/or -XL. However, you can
change this setting for -L, for example if you want to take the INTERSECTION of the sets instead. E.g. to
perform the analysis only on chromosome 1 exomes, you could specify -L exomes.intervals -L 1 --interval-set-rule
INTERSECTION. However, it is not possible to modify the merging approach for intervals passed using -XL (they will
always be merged using UNION).
Note that if you specify both -L and -XL, the -XL interval set will be subtracted from the -L interval set.
The --interval-set-rule argument is an enumerated type (IntervalSetRule), which can have one of the following values:
- UNION
- Take the union of all intervals
- INTERSECTION
- Take the intersection of intervals (the subset that overlaps all intervals specified)
IntervalSetRule UNION
--intervals / -L
One or more genomic intervals over which to operate
List[String] []
--lenient / -LE
Lenient processing of VCF files
boolean false
--output / -O
The combined GVCF output file
R File null
--pedigree / -ped
Pedigree file for determining the population "founders"
File null
--QUIET / NA
Whether to suppress job-summary info on System.err.
Boolean false
--read-filter / -RF
Read filters to be applied before analysis
List[String] []
--read-index / -read-index
Indices to use for the read inputs. If specified, an index must be provided for every read input and in the same order as the read inputs. If this argument is not specified, the path to the index for each input will be inferred automatically.
List[String] []
--read-validation-stringency / -VS
Validation stringency for all SAM/BAM/CRAM/SRA files read by this program. The default stringency value SILENT can improve performance when processing a BAM file in which variable-length data (read, qualities, tags) do not otherwise need to be decoded.
The --read-validation-stringency argument is an enumerated type (ValidationStringency), which can have one of the following values:
- STRICT
- LENIENT
- SILENT
ValidationStringency SILENT
--reference / -R
Reference sequence file
R String null
--seconds-between-progress-updates / -seconds-between-progress-updates
Output traversal statistics every time this many seconds elapse
double 10.0 [ [ -∞ ∞ ] ]
--sequence-dictionary / -sequence-dictionary
Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file.
String null
--showHidden / -showHidden
display hidden arguments
boolean false
--sites-only-vcf-output / NA
If true, don't emit genotype fields when writing vcf file output.
boolean false
--TMP_DIR / NA
Undocumented option
List[File] []
--use-jdk-deflater / -jdk-deflater
Whether to use the JdkDeflater (as opposed to IntelDeflater)
boolean false
--use-jdk-inflater / -jdk-inflater
Whether to use the JdkInflater (as opposed to IntelInflater)
boolean false
--variant / -V
One or more VCF files containing variants
R List[String] []
--verbosity / -verbosity
Control verbosity of logging.
The --verbosity argument is an enumerated type (LogLevel), which can have one of the following values:
- ERROR
- WARNING
- INFO
- DEBUG
LogLevel INFO
--version / NA
display the version number for this tool
boolean false
GATK version 4.0.5.0 built at 25-10-2019 02:10:54.
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