Problem:
matchToMatch transition calculation was wrong resulting in transition probabilites coming out of the Match state that added more than 1.
Reports:
https://www.pivotaltracker.com/s/projects/793457/stories/62471780https://www.pivotaltracker.com/s/projects/793457/stories/61082450
Changes:
The transition matrix update code has been moved to a common place in PairHMMModel to dry out its multiple copies.
MatchToMatch transtion calculation has been fixed and implemented in PairHMMModel.
Affected integration test md5 have been updated, there were no differences in GT fields and example differences always implied
small changes in likelihoods that is what is expected.
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
* Refactoring implementations of readHeader(LineReader) -> readActualHeader(LineIterator), including nullary implementations where applicable.
* Galvanizing fo generic types.
* Test fixups, mostly to pass around LineIterators instead of LineReaders.
* New rev of tribble, which incorporates a fix that addresses a problem with TribbleIndexedFeatureReader reading a header twice in some instances.
* New rev of sam, to make AbstractIterator visible (was moved from picard -> sam in Tribble API refactor).
-- Assembly graph building now returns an object that describes whether the graph was successfully built and has variation, was succesfully built but didn't have variation, or truly failed in construction. Fixing an annoying bug where you'd prefectly assembly the sequence into the reference graph, but then return a null graph because of this, and you'd increase your kmer because it null was also used to indicate assembly failure
--
-- Output format looks like:
20 10026072 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,120
20 10026073 . A <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,119
20 10026074 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,121
20 10026075 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,119
20 10026076 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,120
20 10026077 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:3,0:3:9:0,9,120
20 10026078 . C <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:5,0:5:15:0,15,217
20 10026079 . A <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:6,0:6:18:0,18,240
20 10026080 . G <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:6,0:6:18:0,18,268
20 10026081 . T <NON_REF> . . . GT:AD:DP:GQ:PL 0/0:7,0:7:21:0,21,267
We use a symbolic allele to indicate that the site is hom-ref, and because we have an ALT allele we can provide AD and PL field values. Currently these are calculated as ref vs. any non-ref value (mismatch or insertion) but doesn't yet account properly for alignment uncertainty.
-- Can we enabled for single samples with --emitRefConfidence (-ERC).
-- This is accomplished by realigning the each read to its most likley haplotype, and then evaluting the resulting pileups over the active region interval. The realignment is done by the HaplotypeBAMWriter, which now has a generalized interface that lets us provide a ReadDestination object so we can capture the realigned reads
-- Provide access to the more raw LocusIteratorByState constructor so we can more easily make them programmatically without constructing lots of misc. GATK data structures. Moved the NO_DOWNSAMPLING constant from LIBSDownsamplingInfo to LocusIteratorByState so clients can use it without making LIBSDownsamplingInfo a public class.
-- Includes GVCF writer
-- Add 1 mb of WEx data to private/testdata
-- Integration tests for reference model output for WGS and WEx data
-- Emit GQ block information into VCF header for GVCF mode
-- OutputMode from StandardCallerArgumentCollection moved to UnifiedArgumentCollection as its no longer relevant for HC
-- Control max indel size for the reference confidence model from the command line. Increase default to 10
-- Don't use out_mode in HaplotypeCallerComplexAndSymbolicVariantsIntegrationTest
-- Unittests for ReferenceConfidenceModel
-- Unittests for new MathUtils functions
There are a few pipeline test classes that do not run Queue, but are
classified as pipeline tests because they submit farm jobs. Make these
unconventional pipeline tests respect the pipeline test dry run setting.
The migration of org.broadinstitute.variant into the Picard repo is
complete. This commit deletes the org.broadinstitute.variant sources
from our repo and replaces it with a jar built from a checkout of the
latest Picard-public svn revision.
-- Underlying system now uses long nano times to be more consistent with standard java practice
-- Updated a few places in the code that were converting from nanoseconds to double seconds to use the new nanoseconds interface directly
-- Bringing us to 100% test coverage with clover with AutoFormattingTimeUnitTest
-- Check if a traversal error occurred in the last shard
-- Catch ExecutionException from the TreeReducer and throw as our HMS execption
-- ShardTraverser just throws the exception as formatted by the HMS, rather than wrapping it as a RuntimeException itself
-- EngineFeaturesIntegrationTests now uses public exampleFASTA (faster), and does 1000x iterations (slower)
-- refactored allele clipping / padding code into VCFAlleleClipping class, and added much needed docs and TODOs for methods dev guys
-- Added real unit tests for (some) clipping operations in VCFUtilsUnitTest
-- Created public static UnifiedGenotyper.getHeaderInfo that loads UG standard header lines, and use this in tools like PoolCaller
-- Created VCFStandardHeaderLines class that keeps standard header lines in the GATK in a single place. Provides convenient methods to add these to a header, as well as functionality to repair standard lines in incoming VCF headers
-- VCF parsers now automatically repair standard VCF header lines when reading the header
-- Updating integration tests to reflect header changes
-- Created private and public testdata directories (public/testdata and private/testdata). Updated tests to use test
-- SelectHeaders now always updates the header to include the contig lines
-- SelectVariants add UG header lines when in regenotype mode
-- Renamed PHRED_GENOTYPE_LIKELIHOODS_KEY to GENOTYPE_PL_KEY
-- Bugfix in BCF2 to handle lists of null elements (can happen in genotype field values from VCFs)
-- Throw error when VCF has unbounded non-flag values that don't have = value bindings
-- By default we no longer allow writing of BCF2 files without contig lines in the header
-- The GATK VCFWriter now enforces by default that all INFO, FILTER, and FORMAT fields be properly defined in the header. This helps avoid some of the low-level errors I saw in SelectVariants. This behavior can be disable in the engine with the --allowMissingVCFHeaders argument
-- Fixed broken annotations in TandemRepeat, which were overwriting AD instead of defining RPA
-- Optimizations to VariantEval, removing some obvious low-hanging fruit all in the subsetting of variants by sample
-- SelectVariants header fixes -- Was defining DP for the info field as a FORMAT field, as for AC, AF, and AN original
-- Performance optimizations in BCF2 codec and writer
-- using arrays not lists for intermediate data structures
-- Create once and reuse an array of GenotypeBuilders for the codec, avoiding reallocating this data structure over and over
-- VCFHeader (which needs a complete rewrite, FYI Eric)
-- Warn and fix on the way flag values with counts > 0
-- GenotypeSampleNames are now stored as a List as they are ordered, and the set iteration was slow. Duplicates are detected once at header creation.
-- Explicitly track FILTER fields for efficient lookup in their own hashmap
-- Automatically add PL field when we see a GL field and no PL field
-- Added get and has methods for INFO, FILTER, and FORMAT fields
-- No longer add AC and AF values to the INFO field when there's no ALT allele
-- Memory efficient comparison of VCF and BCF files for shadow BCF testing. Now there's no (memory) constraint on the size of the files we can compare
-- Because of VCF's limited floating point resolution we can only use 1 sig digit for comparing doubles between BCF and VCF
-- BCFFieldEncoder and writers divide up the task of formatting values (atomic or vector, ints, strings, floats, etc) from the task of writing these out at the sites or genotypes level.
-- Allows us to create efficient encoders for specific combinations of header fields, such as int[] encoded values with exactly 3 values
-- Currently only used for INFO fields, but subsequent commit will include optimized genotype field encoder
-- Allowed us to naturally support encoding of lists of strings
-- Bugfixes in VariantContextUtils introduced in genotype -> genotypebuilder conversion
-- Fixes for integration test failures
-- Enabling contig updates
-- WalkerTest now prints out relative paths where possible to make cut/paste/run easier
Instead of creating a supposed network temporary directory locally which then fails when remote nodes try to access the non-existant dir, now checking to see if they network directory is available and throwing a SkipException to bypass the test when it cannot be run.
TODO: Throw similar SkipExceptions when fastas are not available. Right now instead of skipping the test or failing fast the REQUIRE_NETWORK_CONNECTION=false means that the errors popup later when the networked fastas aren't found.
-- VCFWriter / codec now passes the same rigorous UnitTest as the BCF2 writer / codec. As part of this we now can only test doubles for equivalence in VCFs to 1e-2 (not exactly impressive)
-- This version of BCF should actually work properly for most files, assuming headers are properly defined.
-- Lots of bug fixes to BCF2 codec
-- Genotype getPhredScaledQual is now an int, returning -1 if there's no QUAL. NOTE THIS SEMANTICS change
-- Equals() method for GenotypeLikelihoods, using PLs.
-- VCFCodec now longer adds empty bindings to missing input field values. NOTE THIS CHANGE
-- VCs can be marked as fully decoded, so that when fullyDecode() is called it returns itself, instead of doing the decoding work. The BCF2 codec now makes VCs marked as fully decoded
-- stringToBytes returns empty list for null or "" string in BCF2Encoder
-- Proper handling of genotype ordering in BCF2 reader / writer
-- Removed the crazy slow noDups and sameSamples tests that were slowing down unit and integration tests totally unnecessarily
-- Many failing MD5s now due to double -> int change in GQ, will update later
-- Fully working version
-- Use -generateShadowBCF to write out foo.bcf as well as foo.vcf anywhere you use -o foo.vcf
-- Moved MedianUnitTest to its proper home in Utils
-- Added reportng to ivy and testng, so build/report/X/html/ is a nicely formatted output for Unit and Integration tests. From this website it's easy to see md5 diffs, etc. This is a vastly better way to manage unit and integration test output
*** WAY FASTER ***
-- 3x performance for multiple sample analysis with 1000 samples
-- Analyzing 1MB of the ESP call set (3100 samples) takes 40 secs, compared to several minutes in the previous version
-- According to JProfiler all of the runtime is now spent decoding genotypes, which will only get better when we move to BCF2
-- Remove the TableType system, as this was way too complex. No longer possible to embed what were effectively multiple tables in a single Evaluator. You now have to have 1 table per eval
-- Replaced it with @Molten, which allows an evaluator to provide a single Map from variable -> value for analysis. IndelLengthHistogram is now a @Molten data type. GenotypeConcordance is also.
-- No longer allow Evaluators to use private and protected variables at @DataPoints. You get an error if you do.
-- Simplified entire IO system of VE. Refactored into VariantEvalReportWriter.
-- Commented out GenotypePhasingEvaluator, as it uses the retired TableType
-- Stratifications are all fully typed, so it's easy for GATKReports to format them.
-- Removed old VE work around from GATKReportColumn
-- General code cleanup throughout
-- Updated integration tests
-- Refactored some duplicated code (FYI, code duplication = root of all evil) into shared functions
-- Added long-missing integrationtests
-- CHRIS/RYAN -- it would be very good to add an integration test covering external VCF files as I believe we rely on this functionality and it's not tested at all
-Running the GATK with the -et NO_ET or -et STDOUT options now
requires a key issued by us. Our reasons for doing this, and the
procedure for our users to request keys, are documented here:
http://www.broadinstitute.org/gsa/wiki/index.php/Phone_home
-A GATK user key is an email address plus a cryptographic signature
signed using our private key, all wrapped in a GZIP container.
User keys are validated using the public key we now distribute with
the GATK. Our private key is kept in a secure location.
-Keys are cryptographically secure in that valid keys definitely
came from us and keys cannot be fabricated, however keys are not
"copy-protected" in any way.
-Includes private, standalone utilities to create a new GATK user key
(GenerateGATKUserKey) and to create a new master public/private key
pair (GenerateKeyPair). Usage of these tools will be documented on
the internal wiki shortly.
-Comprehensive unit/integration tests, including tests to ensure the
continued integrity of the GATK master public/private key pair.
-Generation of new user keys and the new unit/integration tests both
require access to the GATK private key, which can only be read by
members of the group "gsagit".
-- ReadGroupProperties: Emits a GATKReport containing read group, sample, library, platform, center, median insert size and median read length for each read group in every BAM file.
-- Median tool that collects up to a given maximum number of elements and returns the median of the elements.
-- Unit and integration tests for everything.
-- Making name of TestProvider protected so subclasses and override name more easily
Eric reported this bug due to the reduced reads failing with an index out of bounds on what we thought was a deletion, but turned out to be a read starting with insertion.
* Refactored PileupElement to distinguish clearly between deletions and read starting with insertion
* Modified ExtendedEventPileup to correctly distinguish elements with deletion when creating new pileups
* Refactored most of the lazyLoadNextAlignment() function of the LocusIteratorByState for clarity and to create clear separation between what is a pileup with a deletion and what's not one. Got rid of many useless if statements.
* Changed the way LocusIteratorByState creates extended event pileups to differentiate between insertions in the beginning of the read and deletions.
* Every deletion now has an offset (start of the event)
* Fixed bug when LocusITeratorByState found a read starting with insertion that happened to be a reduced read.
* Separated the definitions of deletion/insertion (in the beginning of the read) in all UG annotations (and the annotator engine).
* Pileup depth of coverage for a deleted base will now return the average coverage around the deletion.
* Indel ReadPositionRankSum test now uses the deletion true offset from the read, changed all appropriate md5's
* The extra pileup elements now properly read by the Indel mode of the UG made any subsequent call have a different random number and therefore all RankSum tests have slightly different values (in the 10^-3 range). Updated all appropriate md5s after extremely careful inspection -- Thanks Ryan!
phew!
-- Missing BAMs were appearing as StingExceptions
-- Missing VCFs were showing up as CommandLineErrors, but it's clearer for them to be CouldNotReadInputFile exceptions
-- Added integration tests to ensure missing BAMs, VCFs, and -L files are properly thrown as CouldNotReadInputFile exceptions
-- Added path to standard b37 BAM to BaseTest
-- Cleaned up code in SAMDataSource, removing my parallel loading code as this just didn't prove to be useful.
Creating a single temporary directory per ant test run instead of a putting temp files across all runs in the same directory.
Updated various tests for above items and other small fixes.
PreQC parses file with spaces in sample names by using tabs only.
PostQC allows passing the file names for the evals so that flanks can be evaled.
BaseTest's network temp dir now adds the user name to the path so files aren't created in the root.
HybridSelectionPipeline:
- Updated to latest versions of reference data.
- Refactored Picard parsing code replacing YAML.
-- VariantSummary now includes novelty of CNVs by reciprocal overlap detection using the standard variant eval -knownCNVs argument
-- Genericizes loading for intervals into interval tree by chromosome
-- GenomeLoc methods for reciprocal overlap detection, with unit tests
System has the concept of a local and a global MD5 db. The local one is like it operated previously. The global one lives in /humgen/gsa-hpprojects/GATK/data/integrationtests. If the system can find this directory then MD5s will also be read / written to this location. This means that gsabamboo will print differences as appropriate. And all users will in effect have access to a complete history of MD5 file results.
A few minor code reshuffles changed VariantRecalibration and VCFHeader test files.
printSummaryReport now uses GATKReport for nice formating
Moved print formatting arguments into inner class provided to printing functions themselves, not the class
BAMDiffableReader only reads 1000 entries to avoid performance issue. Work around for BAM files with non-unique names
Uncommented all of the incorrectly commented out CombineVariants integrationtests
BaseTest now uses DiffEngine to provide inline differences to VCF and BAM files
Valentin Ruano-Rubio
Michael McCowan
Mark DePristo
David Roazen
Mauricio Carneiro
Khalid Shakir
Guillermo del Angel
Ryan Poplin