The tests that access the knowledge base are interfering with the basic
ability to run the unit/integration test suite to completion -- these
few tests often take hours to complete.
Created a new class of test ("KnowledgeBaseTest") that runs separately
from the unit/integration test suite, with corresponding build target.
A new bamboo plan will be set up to run these tests independently so
that they don't interfere with unit/integration testing.
With this change, plus the recent changes to the parallel test runner,
unit/integration test suite runtime should be back down to ~30 minutes
on average.
-Run with -W 240 to give tests more time to complete and hopefully
stop jobs from getting killed with TERM_RUNLIMIT
-Switch to /humgen/gsa-hpprojects for test working directories, since
/broad/hptmp has been unacceptably slow lately
Time to create test working directory, 12/5/13:
/broad/hptmp: 19 minutes
/humgen/gsa-hpprojects: 4 minutes
Previously, we would strip out the PLs and AD values since they were no longer accurate. However, this is not ideal because
then that information is just lost and 1) users complain on the forum and post it as a bug and 2) it gives us problems in both
the current and future (single sample) calling pipelines because we subset samples/alleles all the time and lose info.
Now the PLs and AD get correctly selected down.
While I was in there I also refactored some related code in subsetDiploidAlleles(). There were no real changes there - I just
broke it out into smaller chunks as per our best practices.
Added unit tests and updated integration tests.
Addressed reviews.
To active this feature add '--likelihoodCalculationEngine GraphBased' to the HC command line.
New HC Options (both Advanced and Hidden):
==========================================
--likelihoodCalculationEngine PairHMM/GraphBased/Random (default PairHMM)
Specifies what engine should be used to generate read vs haplotype likelihoods.
PairHMM : standard full-PairHMM approach.
GraphBased : using the assembly graph to accelarate the process.
Random : generate random likelihoods - used for benchmarking purposes only.
--heterogeneousKmerSizeResolution COMBO_MIN/COMBO_MAX/MAX_ONLY/MIN_ONLY (default COMBO_MIN)
It idicates how to merge haplotypes produced using different kmerSizes.
Only has effect when used in combination with (--likelihooCalculationEngine GraphBased)
COMBO_MIN : use the smallest kmerSize with all haplotypes.
COMBO_MAX : use the larger kmerSize with all haplotypes.
MIN_ONLY : use the smallest kmerSize with haplotypes assembled using it.
MAX_ONLY : use the larger kmerSize with haplotypes asembled using it.
Major code changes:
===================
* Introduce multiple likelihood calculation engines (before there was just one).
* Assembly results from different kmerSies are now packed together using the AssemblyResultSet class.
* Added yet another PairHMM implementation with a different API in order to spport
local PairHMM calculations, (e.g. a segment of the read vs a segment of the haplotype).
Major components:
================
* FastLoglessPairHMM: New pair-hmm implemtation using some heuristic to speed up partial PairHMM calculations
* GraphBasedLikelihoodCalculationEngine: delegates onto GraphBasedLikelihoodCalculationEngineInstance the exectution
of the graph-based likelihood approach.
* GraphBasedLikelihoodCalculationEngineInstance: one instance per active-region, implements the graph traversals
to calcualte the likelihoods using the graph as an scafold.
* HaplotypeGraph: haplotype threading graph where build from the assembly haplotypes. This structure is the one
used by GraphBasedLikelihoodCalculationEngineInstance to do its work.
* ReadAnchoring and KmerSequenceGraphMap: contain information as how a read map on the HaplotypeGraph that is
used by GraphBasedLikelihoodCalcuationEngineInstance to do its work.
Remove mergeCommonChains from HaplotypeGraph creation
Fixed bamboo issues with HaplotypeGraphUnitTest
Fixed probrems with HaplotypeCallerIntegrationTest
Fixed issue with GraphLikelihoodVsLoglessAccuracyIntegrationTest
Fixed ReadThreadingLikelihoodCalculationEngine issues
Moved event-block iteration outside GraphBased*EngineInstance
Removed unecessary parameter from ReadAnchoring constructor.
Fixed test problem
Added a bit more documentation to EventBlockSearchEngine
Fixing some private - protected dependency issues
Further refactoring making GraphBased*Instance and HaplotypeGraph slimmer. Addressed last pull request commit comments
Fixed FastLoglessPairHMM public -> protected dependency
Fixed probrem with HaplotypeGraph unit test
Adding Graph-based likelihood ratio calculation to HC
To active this feature add '--likelihoodCalculationEngine GraphBased' to the HC command line.
New HC Options (both Advanced and Hidden):
==========================================
--likelihoodCalculationEngine PairHMM/GraphBased/Random (default PairHMM)
Specifies what engine should be used to generate read vs haplotype likelihoods.
PairHMM : standard full-PairHMM approach.
GraphBased : using the assembly graph to accelarate the process.
Random : generate random likelihoods - used for benchmarking purposes only.
--heterogeneousKmerSizeResolution COMBO_MIN/COMBO_MAX/MAX_ONLY/MIN_ONLY (default COMBO_MIN)
It idicates how to merge haplotypes produced using different kmerSizes.
Only has effect when used in combination with (--likelihooCalculationEngine GraphBased)
COMBO_MIN : use the smallest kmerSize with all haplotypes.
COMBO_MAX : use the larger kmerSize with all haplotypes.
MIN_ONLY : use the smallest kmerSize with haplotypes assembled using it.
MAX_ONLY : use the larger kmerSize with haplotypes asembled using it.
Major code changes:
===================
* Introduce multiple likelihood calculation engines (before there was just one).
* Assembly results from different kmerSies are now packed together using the AssemblyResultSet class.
* Added yet another PairHMM implementation with a different API in order to spport
local PairHMM calculations, (e.g. a segment of the read vs a segment of the haplotype).
Major components:
================
* FastLoglessPairHMM: New pair-hmm implemtation using some heuristic to speed up partial PairHMM calculations
* GraphBasedLikelihoodCalculationEngine: delegates onto GraphBasedLikelihoodCalculationEngineInstance the exectution
of the graph-based likelihood approach.
* GraphBasedLikelihoodCalculationEngineInstance: one instance per active-region, implements the graph traversals
to calcualte the likelihoods using the graph as an scafold.
* HaplotypeGraph: haplotype threading graph where build from the assembly haplotypes. This structure is the one
used by GraphBasedLikelihoodCalculationEngineInstance to do its work.
* ReadAnchoring and KmerSequenceGraphMap: contain information as how a read map on the HaplotypeGraph that is
used by GraphBasedLikelihoodCalcuationEngineInstance to do its work.
Remove mergeCommonChains from HaplotypeGraph creation
Fixed bamboo issues with HaplotypeGraphUnitTest
Fixed probrems with HaplotypeCallerIntegrationTest
Fixed issue with GraphLikelihoodVsLoglessAccuracyIntegrationTest
Fixed ReadThreadingLikelihoodCalculationEngine issues
Moved event-block iteration outside GraphBased*EngineInstance
Removed unecessary parameter from ReadAnchoring constructor.
Fixed test problem
Added a bit more documentation to EventBlockSearchEngine
Fixing some private - protected dependency issues
Further refactoring making GraphBased*Instance and HaplotypeGraph slimmer. Addressed last pull request commit comments
Fixed FastLoglessPairHMM public -> protected dependency
Fixed probrem with HaplotypeGraph unit test
-- For very large whole genome datasets with over 2M variants overlapping the training data randomly downsample the training set that gets used to build the Gaussian mixture model.
-- Annotations are ordered by the difference in means between known and novel instead of by their standard deviation.
-- Removed the training set quality score threshold.
-- Now uses 2 gaussians by default for the negative model.
-- Num bad argument has been removed and the cutoffs are now chosen by the model itself by looking at the LOD scores.
-- Model plots are now generated much faster.
-- Stricter threshold for determining model convergence.
-- All VQSR integration tests change because of these changes to the model.
-- Add test for downsampling of training data.
For reads with high MQs (greater than max byte) the MQ was being treated as negative and failing
the min MQ filter.
Added unit test.
Delivers PT#61567540.
His code was excessively clipping reads because it was looking at their cigar string instead of just
the read length. This meant that it was basically impossible to call large deletions in UG even with
perfect evidence in the reads (as reported by Craig D).
Integration tests change because (IMO after looking at sites in IGV) reads with indels similar to the one
being genotyped used to be given too much likelihood and now give less.
Added unit tests for new methods.
CalculatePosteriors enables the user to calculate genotype likelihood posteriors (and set genotypes accordingly) given one or more panels containing allele counts (for instance, calculating NA12878 genotypes based on 1000G EUR frequencies). The uncertainty in allele frequency is modeled by a Dirichlet distribution (parameters being the observed allele counts across each allele), and the genotype state is modeled by assuming independent draws (Hardy-Weinberg Equilibrium). This leads to the Dirichlet-Multinomial distribution.
Currently this is implemented only for ploidy=2. It should be straightforward to generalize. In addition there's a parameter for "EM" that currently does nothing but throw an exception -- another extension of this method is to run an EM over the Maximum A-Posteriori (MAP) allele count in the input sample as follows:
while not converged:
* AC = [external AC] + [sample AC]
* Prior = DirichletMultinomial[AC]
* Posteriors = [sample GL + Prior]
* sample AC = MLEAC(Posteriors)
This is more useful for large callsets with small panels than for small callsets with large panels -- the latter of these being the more common usecase.
Fully unit tested.
Reviewer (Eric) jumped in to address many of his own comments plus removed public->protected dependencies.
There was already a note in the code about how wrong the implementation was.
The bad code was causing a single-node graph to get cleaned up into nothing when pruning tails.
Delivers PT #61069820.
Eric Banks
David Roazen
Geraldine Van der Auwera
amilev
Joel Thibault
Mauricio Carneiro
Valentin Ruano Rubio
Ryan Poplin
Chris Hartl