Combine segmented gCNV VCFs.

Category Structural Variant Discovery

---

Overview

Merge GCNV segments VCFs This tool takes in segmented VCFs produced by {@link PostprocessGermlineCNVCalls}. For single-sample input VCFs, the tool defragments CNV calls by merging adjacent events within the default or specified fractional padding margins. For distinct samples, the tool clusters events that meet the reciprocal overlap requirement. Output is a multi-sample VCF with site allele counts and frequencies (AC, AF). This tool can also be run on multiple multi-sample VCFs, as in a hierarchical gather for large cohorts. In this case, defragmentation is not preformed because it is assumed that single-sample defragmentation occurred during the initial tool invocation that produced the multi-sample VCF.

Required inputs

• Reference fasta
• Segmented VCFs, single-sample or multi-sample, from {@link PostprocessGermlineCNVCalls}
• The interval list used by {@link GermlineCNVCaller} for calling the input VCFs
• A pedigree file with an entry giving the sex of each sample

Output

A single multi-sample VCF with genotypes and copy numbers

Usage example

   gatk JointGermlineCNVSegmentation \
         -R reference.fasta
         -V sample1.vcf.gz
         -V sample2.vcf.gz
         --model-call-intervals .filtered.interval_list
         --pedigree XandYassignments.ped
         -O clustered.vcf.gz
 

Caveats

• All input samples are required to be present in the pedigree file
• Quality scores are not output, but can be recalculated based on the updated event boundaries with {@link PostprocessGermlineCNVCalls}
• Multi-sample input VCFs are assumed to have been generated by this tool and already defragmented
• This tool only supports mammalian genomes with XX/XY sex determination.

---

Additional Information

Read filters

This Read Filter is automatically applied to the data by the Engine before processing by JointGermlineCNVSegmentation.

• WellformedReadFilter

JointGermlineCNVSegmentation 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		The combined output VCF
--pedigree  -ped		Pedigree file for samples
--reference  -R		Reference sequence file
--variant  -V		One or more VCF files containing variants
Optional Tool Arguments
--alt-allele-summary-strategy	COMMON_SUBTYPE	Strategy to use for choosing a representative alt allele for non-CNV biallelic sites with different subtypes.
--arguments_file		read one or more arguments files and add them to the command line
--autosomal-ref-copy-number	2	Reference copy-number on autosomal intervals.
--breakpoint-summary-strategy	MEDIAN_START_MEDIAN_END	Strategy to use for choosing a representative value for a breakpoint cluster.
--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).
--clustering-breakend-window	0	Cluster events whose endpoints are within this distance of each other
--clustering-interval-overlap	0.8	Minimum interval reciprocal overlap for clustering
--clustering-size-similarity	0.0	Minimum size similarity for clustering
--defragmentation-padding-fraction	0.25	Extend events by this fraction on each side when determining overlap to merge
--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!
--gcs-max-retries  -gcs-retries	20	If the GCS bucket channel errors out, how many times it will attempt to re-initiate the connection
--gcs-project-for-requester-pays		Project to bill when accessing "requester pays" buckets. If unset, these buckets cannot be accessed. User must have storage.buckets.get permission on the bucket being accessed.
--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
--min-sample-set-fraction-overlap	0.0	Minimum fraction of common samples for two variants to cluster together
--minimum-qs-score	20	Minimum QS score to combine a variant segment
--model-call-intervals		gCNV model intervals created with the FilterIntervals tool.
--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		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
--max-variants-per-shard	0	If non-zero, partitions VCF output into shards, each containing up to the given number of records.
--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		Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file.
--tmp-dir		Temp directory to use.
--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
--combine-variants-distance	0	Maximum distance for variants to be grouped together
--ignore-variants-starting-outside-interval	false	Restrict variant output to sites that start within provided intervals (only applies when an interval is specified)
--max-distance	2147483647	Maximum distance for variants to be grouped together
--ref-padding	1	Number of bases on either side to expand spanning reference window
--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

---

--alt-allele-summary-strategy

Strategy to use for choosing a representative alt allele for non-CNV biallelic sites with different subtypes.

The --alt-allele-summary-strategy argument is an enumerated type (AltAlleleSummaryStrategy), which can have one of the following values:

MOST_SPECIFIC_SUBTYPE

Use the most specific subtype that doesn't conflict with any of the other alleles. For example, ( INS , INS:MEI:SVA , INS:MEI:LINE ) results in INS:MEI .

COMMON_SUBTYPE

Use subtypes in common among all alleles. For example, ( INS , INS:MEI:SVA , INS:MEI ) results in INS .

AltAlleleSummaryStrategy  COMMON_SUBTYPE

---

--arguments_file

read one or more arguments files and add them to the command line

List[File]  []

---

--autosomal-ref-copy-number

Reference copy-number on autosomal intervals.

int  2  [ [ 0  ∞ ] ]

---

--breakpoint-summary-strategy

Strategy to use for choosing a representative value for a breakpoint cluster.

The --breakpoint-summary-strategy argument is an enumerated type (BreakpointSummaryStrategy), which can have one of the following values:

MEDIAN_START_MEDIAN_END

Use the (first) middle value to summarize cluster starts and ends, such that the start and end were seen in the data

MIN_START_MAX_END

A conservative strategy to summarize a cluster by its smallest extent

MAX_START_MIN_END

A permissive strategy to summarize a cluster by it largest extent

MEAN_START_MEAN_END

Summarize a cluster using the mean value for each end, even if that value was not represented in any sample

REPRESENTATIVE

Picks a single representative call closest to the overall cluster

BreakpointSummaryStrategy  MEDIAN_START_MEDIAN_END

---

--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  [ [ -∞  ∞ ] ]

---

--clustering-breakend-window

Cluster events whose endpoints are within this distance of each other

int  0  [ [ -∞  ∞ ] ]

---

--clustering-interval-overlap

Minimum interval reciprocal overlap for clustering

double  0.8  [ [ -∞  ∞ ] ]

---

--clustering-size-similarity

Minimum size similarity for clustering

double  0.0  [ [ -∞  ∞ ] ]

---

--combine-variants-distance

Maximum distance for variants to be grouped together

int  0  [ [ -∞  ∞ ] ]

---

--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

---

--defragmentation-padding-fraction

Extend events by this fraction on each side when determining overlap to merge

double  0.25  [ [ -∞  ∞ ] ]

---

--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-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

---

--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). strings gathered from the command line -XL argument to be parsed into intervals to exclude

List[String]  []

---

--gatk-config-file

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  [ [ -∞  ∞ ] ]

---

--gcs-project-for-requester-pays

Project to bill when accessing "requester pays" buckets. If unset, these buckets cannot be accessed. User must have storage.buckets.get permission on the bucket being accessed.

String  ""

---

--help / -h

display the help message

boolean  false

---

--ignore-variants-starting-outside-interval

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[GATKPath]  []

---

--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

---

--max-distance

Maximum distance for variants to be grouped together

int  2147483647  [ [ -∞  ∞ ] ]

---

--max-variants-per-shard

If non-zero, partitions VCF output into shards, each containing up to the given number of records.

int  0  [ [ 0  ∞ ] ]

---

--min-sample-set-fraction-overlap

Minimum fraction of common samples for two variants to cluster together

double  0.0  [ [ -∞  ∞ ] ]

---

--minimum-qs-score

Minimum QS score to combine a variant segment

int  20  [ [ -∞  ∞ ] ]

---

--model-call-intervals

gCNV model intervals created with the FilterIntervals tool.

GATKPath  null

---

--output / -O

The combined output VCF

R GATKPath  null

---

--pedigree / -ped

Pedigree file for samples
See https://software.broadinstitute.org/gatk/documentation/article.php?id=7696 for more details on the PED format. Note that each -ped argument can be tagged with NO_FAMILY_ID, NO_PARENTS, NO_SEX, NO_PHENOTYPE to tell the GATK PED parser that the corresponding fields are missing from the ped file.

R GATKPath  null

---

--QUIET

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[GATKPath]  []

---

--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

---

--ref-padding

Number of bases on either side to expand spanning reference window

int  1  [ [ -∞  ∞ ] ]

---

--reference / -R

Reference sequence file

R GATKPath  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.

GATKPath  null

---

--showHidden / -showHidden

display hidden arguments

boolean  false

---

--sites-only-vcf-output

If true, don't emit genotype fields when writing vcf file output.

boolean  false

---

--tmp-dir

Temp directory to use.

GATKPath  null

---

--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[GATKPath]  []

---

--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

display the version number for this tool

boolean  false

---

Return to top

---

GATK version 4.5.0.0 built at Tue, 9 Jan 2024 14:37:17 -0500.