Right now, if you select a multi-sample VCF file down (or one with filters I see) down to a smaller set of samples, and the site isn't polymorphic in that subgroup, then the alt allele is lost. For example, when selecting down NA12878 from the OMNI, I previously received the following VCF:
1 82154 rs4477212 A . . PASS AC=0;AF=0.00;AN=2;CR=100.0;DP=0;GentrainScore=0.7826;HW=1.0 GT:GC 0/0:0.7205
1 534247 SNP1-524110 C . . PASS AC=0;AF=0.00;AN=2;CR=99.93414;DP=0;GentrainScore=0.7423;HW=1.0 GT:GC 0/0:0.6491
1 565286 SNP1-555149 C T . PASS AC=2;AF=1.00;AN=2;CR=98.8266;DP=0;GentrainScore=0.7029;HW=1.0 GT:GC 1/1:0.3471
1 569624 SNP1-559487 T C . PASS AC=2;AF=1.00;AN=2;CR=97.8022;DP=0;GentrainScore=0.8070;HW=1.0 GT:GC 1/1:0.3942
Where the first two records lost the ALT allele, because NA12878 is hom-ref at this site. My change results in a VCF that looks like:
1 82154 rs4477212 A G . PASS AC=0;AF=0.00;AN=2;CR=100.0;DP=0;GentrainScore=0.7826;HW=1.0 GT:GC 0/0:0.7205
1 534247 SNP1-524110 C T . PASS AC=0;AF=0.00;AN=2;CR=99.93414;DP=0;GentrainScore=0.7423;HW=1.0 GT:GC 0/0:0.6491
1 565286 SNP1-555149 C T . PASS AC=2;AF=1.00;AN=2;CR=98.8266;DP=0;GentrainScore=0.7029;HW=1.0 GT:GC 1/1:0.3471
1 569624 SNP1-559487 T C . PASS AC=2;AF=1.00;AN=2;CR=97.8022;DP=0;GentrainScore=0.8070;HW=1.0 GT:GC 1/1:0.3942
The genotype remains unchanged, but the ALT allele is now preserved. I think this is the correct behavior, as reducing samples down shouldn't change the character of the site, only the AC in the subpopulation. This is related to the tricky issue of isPolymorphic() vs. isVariant().
isVariant => is there an ALT allele?
isPolymorphic => is some sample non-ref in the samples?
In part this is complicated as the semantics of sites-only VCFs, where ALT = . is used to mean not-polymorphic. Unfortunately, I just don't think there's a consistent convention right now, but it might be worth at some point to adopt a single approach to handling this. Wiki docs updated.
Does anyone have critical infrastructure that depends on the previous convention? Let me know so we can coordinate the change.
There's a new function subContextFromGenotypes() that also takes a Set<Allele> to handle this type of behavior.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5832 348d0f76-0448-11de-a6fe-93d51630548a
GenomeLocs can officially have any start/stop values from -Inf - +Inf. Bounds w.r.t. the reference are enforced, optionally, by GenomeLocParser. General code cleanup throughout the subsystem.
All validation code for GLs is now centralized, and all I/O systems now validate their inputs. Because of this, the Picard interval processing code has been changed to examine whether an interval is valid, and only keep the valid intervals. Note that the scatter/gather test was changed, because the original hg18 chr20 interval files as actually malformed (all records for some reason where on chr20).
Many interval processing routines were moved to IntervalUtils, as this is their natural home.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5830 348d0f76-0448-11de-a6fe-93d51630548a
Refactored several Interval utilties from GenomeLocParser to IntervalUtils, as one might expect they go
Removed GenomeLoc.clone() method, as this was not correctly implemented, and actually unnecessary, as GenomeLocs are immutable. Several iterator classes have changed to remove their use of clone()
Removed misc. unnecessary imports
Disabled, temporarily, the validating pileup integration test, as it uses reads mapped to an different reference sequence for ecoli, and this now does not satisfy the contracts for GenomeLoc
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5827 348d0f76-0448-11de-a6fe-93d51630548a
Reviewed pipelines with dev team.
HSP updates:
- Calling SNPs and Indels at the same time then using SelectVariants to separate them for filtering
- Moved logs next to the files like in WGP
- Flattened outputs into one directory
- The file names for the final outputs are now <projectName>.vcf and <projectName>.eval
- Updated test to pass the chr20 intervals instead of a boolean
- Removed MultiFCP
WGP updates:
- Only cleaning and calling chromosomes 1-22, X, Y, MT
- Splitting SNPs from indels, filtering indels, then merging the selected SNPs and selected Indels back together to make sure there are no collisions in CombineVariants
- Still running VQSR on the recombined SNPs plus hard filtered indels
- Using hard indel filters from delangel
- Reduced number of tranches with rpoplin
- Changed prior for dbsnp from 10 to 8 with rpoplin
- Assuming identical samples on both CombineVariants
- Explicitly using variant merge option UNION even though it's the default
- Not setting the default genotype merge option PRIORITIZE
- Generating a vcf and eval for each tranche
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5825 348d0f76-0448-11de-a6fe-93d51630548a
and its three or four nearest neighbors could be in memory at once. Tweaking
the iterators to ensure that previous AlignmentContexts don't have strong
references which means that the garbage collector can work effectively to
help us trundle through these regions.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5820 348d0f76-0448-11de-a6fe-93d51630548a
Removed job priority as temp space isn't as tight at the moment and planning on changing the priority interface.
Updated chunk calling with ebanks:
- Using "the bundle" of resources.
- Using dbsnp 132 and 1000G indel RODs for both RTC & IR.
- Using the default maxIntervalSize in RTC.
- Removed use of UG.exactCalculation argument.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5814 348d0f76-0448-11de-a6fe-93d51630548a
Also added more logging when extension generation fails.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5812 348d0f76-0448-11de-a6fe-93d51630548a
This step just changes storage of likelihoods so now we have, instead of an internal matrix, a class member which stores, as a hash table, a mapping from pileup element to an (allele, likelihood) pair. There's no functional change aside from internal data storage.
As a bonus, we get for free a 2-3x improvement in speed in calling because redundant likelihood computations are removed.
Next step will hook this up to, and redefine annotation engine interaction with UG for indel case.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5809 348d0f76-0448-11de-a6fe-93d51630548a
Added doc string for getNBoundRodTracks()
Intermediate commit for CalibrateGenotypeLikelihoods and GenotypeConcordanceTable, so I have a record of my work. Not ready for public consumption. Really looking forward to making local commits so I can track my progress without needing to push incomplete functionality up to the server.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5807 348d0f76-0448-11de-a6fe-93d51630548a
Using hapmap training and truth based on wiki.
Explicitly setting the ts_filter_level even though 99.0 is the default.
Recal file path now ends with with .recal.
Added ar's vcf input.
Omni rod name now omni instead of 1kg.
The VR RodBind tags had spaces in them.
Was passing both the full intervals and the chunk intervals to chunk jobs.
Switched back to chr20 for default since the VR crashes on small intervals sets with "MESSAGE: Matrix is singular."
Log files names based on the file paths + .out.
Added eval statifications by sample based on the Hybrid Selection / Whole Exome pipeline.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5800 348d0f76-0448-11de-a6fe-93d51630548a
Hardcoded the reference and dbsnp since the training rods are also hardcoded, for now.
Changed freeze/chr20 to wg/chr20/cent1 to also test the heaviest known shard.
Other cleanup.
TODO: Memory command line options or have the script figure it out using FLS or similar.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5799 348d0f76-0448-11de-a6fe-93d51630548a
FindLargeShards. Runtime of FindLargeShards on papuan dataset is now 75min.
GATK proper should benefit as well, although the benefits might be so small
as to not be measurable.
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@5798 348d0f76-0448-11de-a6fe-93d51630548a
depristo
rpoplin
kiran
carneiro
kshakir
ebanks
hanna
delangel
asivache
dheiman
chartl