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GroupCompare

Produce a list of candidate variants based on a sample list

Category Specialized/Internal Tools

Overview

This tool is designed to assist with the generation of candidate variants, based on a given group of samples (e.g., list of samples with a phenotype of interest). It will subset the input VCF to just sites variable in your group(s) of interest, creating a subset VCF with pruned alleles and annotations. Optionally, you can provide a reference VCF (e.g., VCF with genotypes in a broader population). As part of the subsetting, the tool adds several additional INFO field annotations, including:

G1_AF: the allele frequency of each allele within the group 1 samples
G1_HOMVAR: the number of G1 samples that are homozygous for the variant
G1_HET: the number of G1 samples that are heterozygous
G1_HOMREF the number of G1 samples that are homozygous ref

These are repeated for group 2 (i.e. G2_AF, G2_HOMVAR) if group 2 is provided. The same is true for the reference VCF, if provided (i.e., REF_AF, REF_HOMVAR). These fields are available for the optional JEXL-based filtering to create a TSV with a subset of high-interest variants.

Usage example:

  java -jar DISCVRseq.jar GroupCompare \
     -R currentGenome.fasta \
     -V myVCF.vcf \
     -RV refVCF.vcf \
     -O output.vcf.gz \
     -G1 'Sample1'
     -G1 'Sample2'
     -G1 'Sample3'
     -G2 'Sample4'
     -G2 'Sample5'

More advanced usage, with JEXL

You can supply a set of JEXL expressions that will be used to write a subset of variants to a TSV file. You can also supply separate select expressions to limit which variants are written to the output VCF.

  java -jar DISCVRseq.jar GroupCompare \
     -R currentGenome.fasta \
     -V myVCF.vcf \
     -RV refVCF.vcf \
     -O output.vcf.gz \
     -OT output.txt \
     -G1 'Sample1'
     -G1 'Sample2'
     -G1 'Sample3'
     -G2 'Sample4'
     -G2 'Sample5'
     -select 'G1_AF < 0.1 && G2_AF > 0.25'
     -table-select 'IMPACT == "HIGH"'
     -table-select 'CADD_PH > 25'
     -F IMPACT
     -F CADD_PH

Additional Information

Genome/Reference Files

Please note that if this tools uses a reference genome, that FASTA must be indexed with samtools and to have a sequence dictionary created with Picard. See here for more information

Read filters

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

WellformedReadFilter

GroupCompare 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
--group1 -G1	[]	Group 1
--output -O	null	File to which variants should be written
--reference -R	null	Reference sequence file
--variant -V	null	A VCF file containing variants
Optional Tool Arguments
--arguments_file	[]	read one or more arguments files and add them to the command line
--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).
--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!
--fields-to-output -F	[]	The names of fields to include in the output table. These follow the same conventions as GATK VariantsToTable
--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.
--group2 -G2	[]	Group 2
--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
--referenceVariants -RV	null	Reference Variants
--select	[]	A filtering expression in terms of either INFO fields or the VariantContext object). If the expression evaluates to true for a variant, this variant will be output in the VCF. If the is omitted, all variants will be output to the VCF
--sites-only-vcf-output	false	If true, don't emit genotype fields when writing vcf file output.
--table-output -OT	null	File to which a table of high-impact variants should be written. This will only be used if one or more JEXL select expressions are provided.
--table-select	[]	A filtering expression in terms of either INFO fields or the VariantContext object). If the expression evaluates to true for a variant, it will output in the tabular output. This does not impact the VCF 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
--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	null	Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file.
--tmp-dir	null	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

--arguments_file / NA

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

List[File] []

--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 [ [ -∞ ∞ ] ]

--combine-variants-distance / NA

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

--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] []

--fields-to-output / -F

The names of fields to include in the output table. These follow the same conventions as GATK VariantsToTable

ArrayList[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 [ [ -∞ ∞ ] ]

--gcs-project-for-requester-pays / NA

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 ""

--group1 / -G1

Group 1

R Set[String] []

--group2 / -G2

Group 2

Set[String] []

--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)

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
INTERSECTION

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 / NA

Maximum distance for variants to be grouped together

int 2147483647 [ [ -∞ ∞ ] ]

--max-variants-per-shard / NA

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

int 0 [ [ 0 ∞ ] ]

--output / -O

File to which variants should be written

R GATKPath 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[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 / NA

Number of bases on either side to expand spanning reference window

int 1 [ [ -∞ ∞ ] ]

--reference / -R

Reference sequence file

R GATKPath null

--referenceVariants / -RV

Reference Variants

FeatureInput[VariantContext] null

--seconds-between-progress-updates / -seconds-between-progress-updates

Output traversal statistics every time this many seconds elapse

double 10.0 [ [ -∞ ∞ ] ]

--select / NA

A filtering expression in terms of either INFO fields or the VariantContext object). If the expression evaluates to true for a variant, this variant will be output in the VCF. If the is omitted, all variants will be output to the VCF

ArrayList[String] []

--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 / NA

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

boolean false

--table-output / -OT

File to which a table of high-impact variants should be written. This will only be used if one or more JEXL select expressions are provided.

GATKPath null

--table-select / -table-select

A filtering expression in terms of either INFO fields or the VariantContext object). If the expression evaluates to true for a variant, it will output in the tabular output. This does not impact the VCF output.

ArrayList[String] []