Calculate genotype posterior probabilities given family and/or known population genotypes
Category Variant Evaluation and Refinement
Overview
Calculate genotype posterior probabilities given family and/or known population genotypesThe tool calculates the posterior genotype probability for each sample genotype in a given VCF format callset. The input variants must present genotype likelihoods generated by HaplotypeCaller, UnifiedGenotyper or other source that provides unbiased genotype likelihoods.
The tool can use priors from three different data sources: (i) one or more supporting germline population callsets with specific annotation(s) if supplied , (ii) the pedigree for a trio if supplied and if the trio is represented in the callset under refinement, and/or (iii) the allele counts of the callset samples themselves given at least ten samples. It is possible to deactivate the contribution of the callset samples with the --ignore-input-samples flag.
For more background information and for mathematical details, see GATK forum article at https://software.broadinstitute.org/gatk/documentation/article?id=11074. Additional GATK mathematical notes are presented as whitepapers in the gatk GitHub repository docs section at https://github.com/broadinstitute/gatk/tree/master/docs.
Inputs
- A VCF with genotype likelihoods, and optionally genotypes, AC/AN fields, or MLEAC/AN fields. The tool will use MLEAC if available or AC if MLEAC is not provided. AN is also required unless genotypes are provided for all samples.
- (Optional) A PED pedigree file containing the description of the relationships between individuals. The tool considers only trio groups. A trio consists of mother-father-child.
Optionally, a collection of VCFs can be provided for the purpose of informing population allele frequency priors. Each of these resource VCFs must satisfy at least one of the following requirement sets:
- AC field and AN field
- MLEAC field and AN field
- Genotypes
Output
A new VCF with the following information:
- Genotype posteriors added to the FORMAT fields ("PP")
- Genotypes and GQ assigned according to these posteriors (note that the original genotype and GQ may change)
- Per-site genotype priors added to the INFO field ("PG")
- (Optional) Per-site, per-trio joint likelihoods (JL) and joint posteriors (JP) given as Phred-scaled probability of all genotypes in the trio being correct based on the PLs for JL and the PPs for JP. These annotations are added to the FORMAT fields.
Notes
By default, priors will be applied to each variant separately, provided each variant features data from at least 10 called samples (no-calls do not count). SNP sites in the input callset that have a SNP at the matching site in the supporting VCF will have priors applied based on the AC from the supporting samples and the input callset unless the --ignore-input-samples flag is used. If a site is not called in the supporting VCF, priors will be applied using the discovered AC from the input samples unless the --discovered-allele-count-priors-off flag is used. For any non-SNP sites in the input callset, flat priors are applied.
For versions of the tool 4.0.5.0+, the tool appropriately applies priors to indels.
If applying family priors, only diploid family genotypes are supported. In addition, family priors only apply to trios represented in both a supplied pedigree and in the callset under refinement. Note, if the pedigree is incomplete, the tools skips calculating family priors. In this case, and in the absence of other refinement, the results will be identical to the input.
Usage examples
Refine genotypes based on the discovered allele frequency in an input VCF containing many samples
gatk --java-options "-Xmx4g" CalculateGenotypePosteriors \ -V multisample_input.vcf.gz \ -O output.vcf.gz
Inform the genotype assignment of a single sample using the 1000G phase 3 samples
gatk --java-options "-Xmx4g" CalculateGenotypePosteriors \ -V sample_input.vcf.gz \ -O sample_output.1000G_PPs.vcf.gz \ -supporting 1000G.phase3.integrated.sites_only.no_MATCHED_REV.hg38.vcf.gz
Apply only family priors to a callset
gatk --java-options "-Xmx4g" CalculateGenotypePosteriors \ -V input.vcf.gz \ -O output.vcf.gz \ -ped family.ped \ --skip-population-priors
Apply frequency and HWE-based priors to the genotypes of a family without including the family allele counts in the allele frequency estimates
gatk --java-options "-Xmx4g" CalculateGenotypePosteriors \ -V input.vcf.gz \ -O output.vcf.gz \ --ignore-input-samples
Calculate the posterior genotypes of a callset, and impose that a variant *not seen* in the external panel is tantamount to being AC=0, AN=5008 within that panel
gatk --java-options "-Xmx4g" CalculateGenotypePosteriors \ -V input.vcf.gz \ -O output.vcf.gz \ -supporting 1000G.phase3.integrated.sites_only.no_MATCHED_REV.hg38.vcf.gz \ --num-reference-samples-if-no-call 2504
Caveat
If applying family priors, only diploid family genotypes are supported
Additional Information
Read filters
This Read Filter is automatically applied to the data by the Engine before processing by CalculateGenotypePosteriors.
CalculateGenotypePosteriors 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 |
File to which variants should be written | ||
| --variant -V |
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). | |
| --de-novo-prior |
1.0E-6 | Prior for de novo mutations | |
| --default-to-allele-count |
false | Use AC rather than MLEAC | |
| --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! | |
| --discovered-allele-count-priors-off |
false | Do not use discovered allele count in the input callset for variants that do not appear in the external callset. | |
| --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. | ||
| --global-prior-indel |
0.001 | Global Dirichlet prior parameters for the indel allele frequency | |
| --global-prior-snp |
0.001 | Global Dirichlet prior parameters for the SNP allele frequency | |
| --help -h |
false | display the help message | |
| --ignore-input-samples |
false | Use external information only | |
| --interval-merging-rule -imr |
ALL | Interval merging rule for abutting intervals | |
| --intervals -L |
One or more genomic intervals over which to operate | ||
| --num-reference-samples-if-no-call |
0 | Number of hom-ref genotypes to infer at sites not present in a panel | |
| --pedigree -ped |
Pedigree file for samples | ||
| --reference -R |
Reference sequence | ||
| --sites-only-vcf-output |
false | If true, don't emit genotype fields when writing vcf file output. | |
| --skip-family-priors |
false | Skip application of family-based priors | |
| --skip-population-priors |
false | Skip application of population-based priors | |
| --supporting-callsets -supporting |
Other callsets to use in generating genotype posteriors | ||
| --use-flat-priors-for-indels -skipIndels |
false | Use flat priors for indels | |
| --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
--arguments_file
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 [ [ -∞ ∞ ] ]
--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
--de-novo-prior
Prior for de novo mutations
The de novo mutation prior -- i.e. the probability that a new mutation occurs. Sensitivity analysis on known de novo
mutations suggests a default value of 10^-6.
double 1.0E-6 [ [ -∞ ∞ ] ]
--default-to-allele-count
Use AC rather than MLEAC
By default the tool looks for MLEAC first, and then falls back to AC if MLEAC is not found. When this
flag is set, the behavior is flipped and the tool looks first for the AC field and then fall back to MLEAC or
raw genotypes.
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
--discovered-allele-count-priors-off
Do not use discovered allele count in the input callset for variants that do not appear in the external callset.
Don't add input sample ACs for variants not seen in the supporting panel. Default is to add discovered AC from input samples
provided there are at least 10 input samples or if num-ref-samples-if-no-call is greater than zero.
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] []
--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 ""
--global-prior-indel
Global Dirichlet prior parameters for the indel allele frequency
Prior indel pseudocounts for Dirichlet distribution of allele frequencies. The posterior distribution is a
Dirichlet with parameters given by pseudocounts plus the number of occurrences in the resource vcfs.
double 0.001 [ [ -∞ ∞ ] ]
--global-prior-snp
Global Dirichlet prior parameters for the SNP allele frequency
Prior SNP pseudocounts for Dirichlet distribution of allele frequencies. The posterior distribution is a
Dirichlet with parameters given by pseudocounts plus the number of occurrences in the resource vcfs.
double 0.001 [ [ -∞ ∞ ] ]
--help / -h
display the help message
boolean false
--ignore-input-samples
Use external information only
When this flag is set, only the AC and AN calculated from external sources will be used, and the calculation
will not use the discovered allele frequency in the callset whose posteriors are being calculated. Useful for
callsets containing related individuals.
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-variants-per-shard
If non-zero, partitions VCF output into shards, each containing up to the given number of records.
int 0 [ [ 0 ∞ ] ]
--num-reference-samples-if-no-call
Number of hom-ref genotypes to infer at sites not present in a panel
When a variant is not seen in a panel, this argument controls whether to infer (and with what effective strength)
that only reference alleles were observed at that site. E.g. "If not seen in 1000Genomes, treat it as AC=0,
AN=2000", where AN=2*nSamples for human autosomes.
int 0 [ [ -∞ ∞ ] ]
--output / -O
File to which variants should be written
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.
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
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
--skip-family-priors
Skip application of family-based priors
Skip application of family-based priors. Note: if pedigree file is absent, family-based priors will always be skipped.
boolean false
--skip-population-priors
Skip application of population-based priors
Skip application of population-based priors
boolean false
--supporting-callsets / -supporting
Other callsets to use in generating genotype posteriors
Supporting external panels. Allele counts from these panels (taken from AC,AN or MLEAC,AN or raw genotypes) will
be used to inform the frequency distribution underlying the genotype priors. These files must be VCF 4.2 spec or later.
List[FeatureInput[VariantContext]] []
--tmp-dir
Temp directory to use.
GATKPath null
--use-flat-priors-for-indels / -skipIndels
Use flat priors for indels
Use flat priors for indels (can be used to replicate the legacy CalculateGenotypePosteriors behavior)
If an input variant contains an indel allele, flat priors will be applied to that site. If a reference panel
variant contains an indel allele, flat priors will be applied instead.
boolean false
--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
A VCF file containing variants
R GATKPath 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 4.2.2.0-SNAPSHOT built at Thu, 19 Aug 2021 09:49:28 -0700.
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