Clusters structural variants
Category Structural Variant Discovery
Overview
Clusters structural variants based on coordinates, event type, and supporting algorithms. Primary use cases include:
- Clustering SVs produced by multiple callers, based on interval overlap, breakpoint proximity, and sample overlap.
- Merging multiple SV VCFs with disjoint sets of samples and/or variants.
- Defragmentation of copy number variants produced with depth-based callers.
Clustering tasks can be accomplished using one of two algorithms. The SINGLE_LINKAGE algorithm produces clusters for which all members cluster with at least one other member. The MAX_CLIQUE algorithm, however, requires that all members cluster with every other member. The latter is in general non-polynomial in time and space but implemented to minimize computations by traversing variants ordered by start position and efficiently finalizing "active" clusters that are determined to be complete.
The tool determines whether two given variants should cluster based following criteria:
- Matching SV type. DEL and DUP are considered matching SV types if --enable-cnv is used and merged into a multi-allelic CNV type.
- Matching breakend strands (BND and INV only)
- Interval reciprocal overlap (inapplicable for BNDs).
- Distance between corresponding event breakends (breakend window).
- Sample reciprocal overlap, based on carrier status determined by available genotypes (GT fields). If no GT fields are called for a given variant, the tool attempts to find carriers based on copy number (CN field) and sample ploidy (as determined by the ECN FORMAT field).
For CNV defragmentation (DEFRAGMENT_CNV algorithm), the tool uses single-linkage clustering based on the following linkage criteria:
- Must be a DEL/DUP/CNV and only be supported by a depth algorithm.
- Matching SV type
- Overlapping after padding both sides of each variant by the fraction of event length specified by --defrag-padding-fraction.
- Sample overlap fraction (described above) specified by --defrag-sample-overlap.
Interval overlap, breakend window, and sample overlap parameters are defined for three combinations of event types using the ALGORITHMS field, which describes the type of evidence that was used to call the variant:
- Depth-only - both variants have solely "depth" ALGORITHMS
- PESR (paired-end/split-read) - both variants have at least one non-depth entry in ALGORITHMS
- Mixed - one variant is depth-only and the other is PESR
Users must supply one or more VCFs containing SVs with the following info fields:
- SVTYPE - event type (DEL, DUP, CNV, INS, INV, BND)
- SVLEN - variant length for INS only, if known
- STRANDS - breakend strands ("++", "+-", "-+", or "--") (BND and INV only)
- CHROM2 / END2 - mate coordinates (BND only)
- ALGORITHMS - list of supporting tools/algorithms. These names may be arbitrary, except for depth-based callers, which should be listed as "depth".
In addition, the following FORMAT fields must be defined:
- GT - genotype alleles
- ECN - expected copy number (i.e. ploidy)
- CN - genotype copy number (DEL/DUP/CNV only)
Note that for CNVs (DEL, DUP, multi-allelic CNV), GT alleles are set according to the CN/ECN fields. In some cases, (e.g. diploid DUPs with CN 4), allele phasing cannot be determined unambiguously and GT is set with no-call alleles.
The tool generates a new VCF with clusters collapsed into single representative records. By default, a MEMBERS field is generated that lists the input variant IDs contained in that record's cluster.
Inputs
- One or more SV VCFs
Output
- Clustered VCF
Usage example
gatk SVCluster \
-V variants.vcf.gz \
-O clustered.vcf.gz \
--algorithm SINGLE_LINKAGE
Additional Information
Read filters
This Read Filter is automatically applied to the data by the Engine before processing by SVCluster.
SVCluster 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 |
Output VCF | ||
| --ploidy-table |
Sample ploidy table (.tsv) | ||
| --reference -R |
Reference sequence file | ||
| --variant -V |
One or more VCF files containing variants | ||
| Optional Tool Arguments | |||
| --algorithm |
SINGLE_LINKAGE | Clustering algorithm | |
| --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 | ||
| --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). | |
| --convert-inv-to-bnd |
false | Convert inversions to BND records | |
| --default-no-call |
false | Default to no-call GT (e.g. ./.) instead of reference alleles (e.g. 0/0) when a genotype is not available | |
| --defrag-padding-fraction |
0.25 | Padding as a fraction of variant length for CNV defragmentation mode. | |
| --defrag-sample-overlap |
0.8 | Minimum sample overlap fraction. Use instead of --depth-sample-overlap in CNV defragmentation mode. | |
| --depth-breakend-window |
0 | Depth/Depth window size for breakend proximity | |
| --depth-interval-overlap |
0.8 | Depth/Depth interval reciprocal overlap fraction | |
| --depth-sample-overlap |
0.0 | Depth/Depth shared sample overlap fraction | |
| --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! | |
| --enable-cnv |
false | Enable clustering DEL/DUP variants together as CNVs (does not apply to CNV defragmentation) | |
| --fast-mode |
false | Fast mode. Drops hom-ref and no-call genotype fields and emits them as no-calls. | |
| --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 | |
| --insertion-length-summary-strategy |
MEDIAN | Strategy to use for choosing a representative value for insertion length when unknown. | |
| --interval-merging-rule -imr |
ALL | Interval merging rule for abutting intervals | |
| --intervals -L |
One or more genomic intervals over which to operate | ||
| --mixed-breakend-window |
1000 | Depth/PESR window size for breakend proximity | |
| --mixed-interval-overlap |
0.8 | PESR/Depth interval reciprocal overlap fraction | |
| --mixed-sample-overlap |
0.0 | Depth/PESR shared sample overlap fraction | |
| --omit-members |
false | Omit cluster member ID annotations | |
| --pesr-breakend-window |
500 | PESR/PESR window size for breakend proximity | |
| --pesr-interval-overlap |
0.5 | PESR/PESR interval reciprocal overlap fraction | |
| --pesr-sample-overlap |
0.0 | PESR/PESR shared sample overlap fraction | |
| --sites-only-vcf-output |
false | If true, don't emit genotype fields when writing vcf file output. | |
| --variant-prefix |
If supplied, generate variant IDs with this prefix | ||
| --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 | |||
| --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
--algorithm
Clustering algorithm
The --algorithm argument is an enumerated type (CLUSTER_ALGORITHM), which can have one of the following values:
- DEFRAGMENT_CNV
- Defragment cnv cluster algorithm.
- SINGLE_LINKAGE
- Single linkage cluster algorithm.
- MAX_CLIQUE
- Max clique cluster algorithm.
CLUSTER_ALGORITHM SINGLE_LINKAGE
--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] []
--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
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 [ [ -∞ ∞ ] ]
--convert-inv-to-bnd
Convert inversions to BND records
When enabled, INV records will be converted to a pairs of BNDs prior to clustering.
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
--default-no-call
Default to no-call GT (e.g. ./.) instead of reference alleles (e.g. 0/0) when a genotype is not available
Default genotypes are assigned when they cannot be inferred from the inputs, such as when VCFs with different
variants and samples are provided.
boolean false
--defrag-padding-fraction
Padding as a fraction of variant length for CNV defragmentation mode.
double 0.25 [ [ -∞ ∞ ] ]
--defrag-sample-overlap
Minimum sample overlap fraction. Use instead of --depth-sample-overlap in CNV defragmentation mode.
double 0.8 [ [ -∞ ∞ ] ]
--depth-breakend-window
Depth/Depth window size for breakend proximity
Maximum allowed distance between endpoints (in bp) to cluster depth-only/depth-only variant pairs.
int 0 [ [ 0 ∞ ] ]
--depth-interval-overlap
Depth/Depth interval reciprocal overlap fraction
Minimum interval reciprocal overlap fraction to cluster depth-only/depth-only variant pairs.
double 0.8 [ [ 0 1 ] ]
--depth-sample-overlap
Depth/Depth shared sample overlap fraction
Minimum carrier sample reciprocal overlap fraction to cluster depth-only/depth-only variant pairs.
double 0.0 [ [ 0 1 ] ]
--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
--enable-cnv
Enable clustering DEL/DUP variants together as CNVs (does not apply to CNV defragmentation)
When enabled, DEL and DUP variants will be clustered together. The resulting records with have an SVTYPE of CNV.
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] []
--fast-mode
Fast mode. Drops hom-ref and no-call genotype fields and emits them as no-calls.
Results in substantial space and time costs for large sample sets by clearing genotypes that are not needed for
clustering, but any associated annotation fields will be set to null in the output.
boolean false
--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
--input / -I
BAM/SAM/CRAM file containing reads
List[GATKPath] []
--insertion-length-summary-strategy
Strategy to use for choosing a representative value for insertion length when unknown.
The --insertion-length-summary-strategy argument is an enumerated type (InsertionLengthSummaryStrategy), which can have one of the following values:
- MEDIAN
- MEAN
- MIN
- MAX
- UNDEFINED
InsertionLengthSummaryStrategy MEDIAN
--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-variants-per-shard
If non-zero, partitions VCF output into shards, each containing up to the given number of records.
int 0 [ [ 0 ∞ ] ]
--mixed-breakend-window
Depth/PESR window size for breakend proximity
Maximum allowed distance between endpoints (in bp) to cluster depth-only/PESR variant pairs.
int 1000 [ [ 0 ∞ ] ]
--mixed-interval-overlap
PESR/Depth interval reciprocal overlap fraction
Minimum interval reciprocal overlap fraction to cluster depth-only/PESR variant pairs.
double 0.8 [ [ 0 1 ] ]
--mixed-sample-overlap
Depth/PESR shared sample overlap fraction
Minimum carrier sample reciprocal overlap fraction to cluster depth-only/PESR variant pairs.
double 0.0 [ [ 0 1 ] ]
--omit-members
Omit cluster member ID annotations
boolean false
--output / -O
Output VCF
R GATKPath null
--pesr-breakend-window
PESR/PESR window size for breakend proximity
Maximum allowed distance between endpoints (in bp) to cluster PESR/PESR variant pairs.
int 500 [ [ 0 ∞ ] ]
--pesr-interval-overlap
PESR/PESR interval reciprocal overlap fraction
Minimum interval reciprocal overlap fraction to cluster PESR/PESR variant pairs.
double 0.5 [ [ 0 1 ] ]
--pesr-sample-overlap
PESR/PESR shared sample overlap fraction
Minimum carrier sample reciprocal overlap fraction to cluster PESR/PESR variant pairs.
double 0.0 [ [ 0 1 ] ]
--ploidy-table
Sample ploidy table (.tsv)
Expected format is tab-delimited and contains a header with the first column SAMPLE and remaining columns
contig names. Each row corresponds to a sample, with the sample ID in the first column and contig ploidy
integers in their respective columns.
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
--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] []
--variant-prefix
If supplied, generate variant IDs with this prefix
String null
--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
GATK version 4.3.0.0 built at Wed, 12 Oct 2022 21:04:44 -0400.
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