-- Multi-allelic variants are split into their bi-allelic version, trimmed, and we attempt to provide a meaningful genotype for NA12878 here. It's not perfect and needs some discussion on how to handle het/alt variants
-- Adding splitInBiallelic funtion to VariantContextUtils as well as extensive unit tests that also indirectly test reverseTrimAlleles (which worked perfectly FYI)
-- Idea is simply to create a persistent database of all TP/FP sites on chr20 in NA12878. Individual callsets can be imported, and a consensus algorithm is run over all callsets in the database to create a consensus collection, which can be used to assess NA12878 callsets for GATK and methods development
-- Framework for representing simple VariantContexts and Genotypes in MongoDB, querying for records, and iterating over them in the GATK
-- Not hooked up to Tribble, but could be done reasonably easily now (future TODO)
-- Tools to import callsets, create consensus callsets, import and export reviews
-- Scripts to reset the knowledge base and repopulate it with the standard data files (Eric will expand)
-- Actually scales to all of chr20, includes AssessNA12878 that reads a VCF and itemizes it against the truth data set
-- ImportCallset can load OMNI, HM3, CEU best practices, mills/devine sites and genotypes, properly marking sites as poly/mono/unk as well as TP/FP/UNK based on command line parameters
-- Added shell scripts that start up a local mongo db, that connect to a local or BI hosted mongo for NA12878.db for debugging, and a setupNA12878db script that can load OMNI, HM3, CEU best practices, Mills/Devine into the db and then update the consensus.
-- Reviewed sites can be exported to a VCF, and imported again, as a mechanism to safely store the only non-recoverable data from the Mongo DB.
-- Created a NA12878DBWalker that manages the outer DB interaction, and that all MongoDB interacting walkers inherit from. Added a NA12878DBArgumentCollection.java consolating all of the common command line arguments (though strictly not necessary as all of this occurs in the root walker)
UnitTests
-- Can connect to a test knowledge base for development and unit testing
-- PolymorphicStatus, TruthStatus, SiteIterator
-- NA12878KBUnitTestBase provides simple utilities for connecting to the test mongo db, getting calls, etc
-- MongoVariantContext tests creation, matching, and encoding -> writing -> read -> decoding from the mongodb
AssessNA12878
-- Generic tool for comparing a NA12878 callset against the knowledge base. See http://gatkforums.broadinstitute.org/discussion/1848/using-the-na12878-knowledge-base for detailed documentation
-- Performs trivial filtering on FS, MQ, QD for SNPs and non-SNPs to separate out variants likely to be filtered from those that are honest-to-goodness FPs
Misc
-- Ability to provide Description for Simplified GATK report
ReduceReads now co-reduces bams if they're passed in toghether with multiple -I. Co-reduction forces every variant region in one sample to be a variant region in all samples.
Also:
* Added integrationtest for co-reduction
* Fixed bug with new no-recalculation implementation of the marksites object where the last object wasn't being removed after finalizing a variant region (updated MD5's accordingly)
DEV-200 #resolve #time 8m
Removed some generics from PluginManager for now until able to figure out syntax for requesting explicit subclass.
QStatusMessenger uses a slightly more primitive Map[String, Seq[RemoteFile]] instead of Map[ArgumentSource, Seq[RemoteFile]].
Added an QCommandPlugin.initScript utility method for handling specialized script types.
numbers larger than 999 in the Errors column were printed out with commas (which looks like a separate column).
This wasn't caught earlier because there are no integration tests covering the csv. I'll add one into unstable in a sec.
-- New tribble library now uses 64 bit sizes. The 26K VCF has so much data that low-level tribble block indices where overflowing their int size values. This includes a to-be-committed tribble jar that fixes this problem
-- See https://jira.broadinstitute.org/browse/GSA-652
-- Minor cleanup of error messages that were useful on the way to solving this monster problem
-- The logic for determining active regions was a bit broken in the HC when intervals were used in the system
-- TraverseActiveRegions now uses the AllLocus view, since we always want to see all reference sites, not just those covered. Simplifies logic of TAR
-- Non-overlapping intervals are always treated as separate objects for determing active / inactive state. This means that each exon will stand on its own when deciding if it should be active or inactive
-- Misc. cleanup, docs of some TAR infrastructure to make it safer and easier to debug in the future.
-- Committing the SingleExomeCalling script that I used to find this problem, and will continue to use in evaluating calling of a single exome with the HC
-- Make sure to get all of the reads into the set of potentially active reads, even for genomic locations that themselves don't overlap the engine intervals but may have reads that overlap the regions
-- Remove excessively expensive calls to check bases are upper cased in ReferenceContext
-- Update md5s after a lot of manual review and discussion with Ryan
-- As one might expect, CachingIndexedFastaSequenceFile now internally upper cases the FASTA reference bases. This is now done by default, unless requested explicitly to preserve the original bases.
-- This is really the correct place to do this for a variety of reasons. First, you don't need to work about upper casing bases throughout the code. Second, the cache is only upper cased once, no matter how often the bases are accessed, which walkers cannot optimize themselves. Finally, this uses the fastest function for this -- Picard's toUpperCase(byte[]) which is way better than String.toUpperCase()
-- Added unit tests to ensure this functionality works correct.
-- Removing unnecessary upper casing of bases in some core GATK tools, now that RefContext guarentees that the reference bases are all upper case.
-- Added contracts to ensure this is the case.
-- Remove a ton of sh*t from BaseUtils that was so old I had no idea what it was doing any longer, and didn't have any unit tests to ensure it was correct, and wasn't used anywhere in our code
-- Providing this optional argument -maxRuntime (in -maxRuntimeUnits units) causes the GATK to exit gracefully when the max. runtime has been exceeded. By cleanly I mean that the engine simply stops at the next available cycle in the walker as through the end of processing had been reached. This means that all output files are closed properly, etc.
-- Emits an info message that looks like "INFO 10:36:52,723 MicroScheduler - Aborting execution (cleanly) because the runtime has exceeded the requested maximum 10.0000 s". Otherwise there's currently no way to differentiate a truly completed run from a timelimit exceeded run, which may be a useful thing for a future update
-- Resolves GSA-630 / GATK max runtime to deal with bad LSA calling?
-- Added new JIRA entry for Ami to restart chr1 macarthur with this argument set to -maxRuntime 1 -maxRuntimeUnits DAYS to see if we can do all of chr1 in one weekend.
-- NCT wasn't previously recognized by Queue as needing more processors per machine. This commit fixes this. Also a potential cause of poor GATKPerformanceOverTime, in that runs with -nct could flood a node and cause it to have hundreds of cores in contention.
Caching and reusing ReadCovariates instances across reads sounds good in theory, but:
-it doesn't work unless you zero out the internal arrays before each read
-the internal arrays must be sized proportionally to the maximum POSSIBLE
recalibrated read length (5000!!!), instead of the ACTUAL read lengths
By contrast, creating a new instance per read is basically equivalent to doing an
efficient low-level memset-style clear on a much smaller array (since we use the actual
rather than the maximum read length to create it). So this should be faster than caching
instances and calling clear() but slower than caching instances and not calling clear().
Credit to Ryan to proposing this approach.
It turns out that pre-allocating the entire tree was too expensive in
terms of memory when using large values for the -mcs and -ics parameters.
Pre-allocating the first two dimensions prevents us from ever locking the
root node during a put(). Contention between threads over lower levels
of the tree should be minimal given that puts are rare compared to gets.
Also output dimensions and pre-allocation info at startup. If pre-allocation
takes longer than usual this gives the user a sense of what is causing the
delay.
-- I'm committing because there's some kind of fundamental problem with the ReadCovariates cache, in that historical data isn't being cleared / computed properly, and I'd rather it fail for a while than leave it in JIRA.
-- The integration tests test the -nct with PrintReads to get 1, 2, 4 and the 4 fails. But that's because of this incorrect calculation
-- Updating GATKPerformanceOverTime with the new @ClassType annotation
Also, fixes to large-scale validation script: lower -minIndelFrac threshold or else we'll kill most indels since default 0.25 is too high for pools, fix also VE stratifications and add one VE run where eval=1KG, comp=pool data and AC stratification based on 1KG annotation
The old BaseRecalibrator walker is and never will be thread-safe, since it's a
LocusWalker that uses read attributes to track state.
ONLY the newer DelocalizedBaseRecalibrator is believed likely to be thread-safe
at this point. It is safe to run the DelocalizedBaseRecalibrator with -nct > 1
for testing purposes, but wait for further testing to be done before using it
for production purposes in multithreaded mode.
The ReadGroupCovariate class was not thread-safe. This led to horrible race conditions
in multithreaded runs of the BQSR where (for example) the same read group could get
inserted into the reverse lookup table twice with different IDs.
Should fix the intermittent crash reported in GSA-492.
-With this change, BQSR performance scales properly by thread rather
than gaining nothing from additional threads.
-Benefits are seen when using either -nt (HierarchicalMicroScheduler) or -nct
(NanoScheduler)
-Removes high-level locks in the recalibration engines and NestedIntegerArray
in favor of maximally-granular locks on and around manipulation of the leaf
nodes of the NestedIntegerArray.
-NestedIntegerArray now creates all interior nodes upfront rather than on
the fly to avoid the need for locking during tree traversals. This uses
more memory in the initial part of BQSR runs, but the BQSR would eventually
converge to use this memory anyway over the course of a typical run.
IMPORTANT NOTE: This does not mean it's safe to run the old BaseRecalibrator
walker with multiple threads. The BaseRecalibrator walker is and will never be
thread-safe, as it's a LocusWalker that uses read attributes to track
state information. ONLY the newer DelocalizedBaseRecalibrator can be made
thread-safe (and will hopefully be made so in my subsequent commits). This
commit addresses performance, not correctness.
Bringing in the following relevant changes:
* Fixes the indel realigner N-Way out null pointer exception DEV-10
* Optimizations to ReduceReads that bring the run time to 1/3rd.
Conflicts:
protected/java/src/org/broadinstitute/sting/gatk/walkers/compression/reducereads/SlidingWindow.java
DEV-10 #resolve #time 2m
-- Included logic to only add priors for alleles with sufficient evidence to be called polymorphic. If no alleles are poly make sure to add priors of first allele
-- There's been no report of problems with the nano scheduled version of TraverseLoci and TraverseReads, so I'm removing the old versions since they are no longer needed
-- Removing unnecessary intermediate base classes
-- GSA-515 / Nanoscheduler GSA-549 / https://jira.broadinstitute.org/browse/GSA-549
-- Updated StandardCallerArgumentCollection to remove MaxAltAllelesForIndels. Previous argument is deprecated with meaningful doc message for people to use maxAltAlleles
-- All constructores, factory methods, and test builders and their users updated to provide just a single argument
-- Updating MD5s for integration tests that change due to genotyping more alleles
-- Adding more alleles to genotyping results in slight changes in the QUAL value for multi-allelic loci where one or more alleles aren't polymorphic. That's simply due to the way that alternative hypotheses contribute as reference evidence against each true allele. The effect can be large (new qual = old qual / 2 in one case here).
-- If we want more precision in our estimates we could decide (Eric, should we discuss?) to actually separately do a discovery phase in the genotyping, eliminate all variants not considered polymorphic, and then do a final round of calling to get the exact QUAL value for only those that are segregating. This would have the value of having the QUAL stay constant as more alleles are genotyped, at the cost of some code complexity increase and runtime. Might be worth it through
-- The old way of overloading constructors and calling super didn't work (might have been a consequence of merge). This is the right way to do the copy constructor with the call to super()
-- Potentially a very fast implementation (it's very clean) but restricted to the biallelic case
-- A starting point for future bi-allelic only optimized (logless) or generalized (bi-allelic general ploidy) implementations
-- Added systematic unit tests covering this implementation, and comparing it to others
-- Uncovered a nasty normalization bug in StateTracker that was capping our likelihoods at 0, even after summing up multiple likelihoods, which is just not safe to do and was causing us to lose likelihood in some cases
-- Removed the restriction that a likelihood be <= 0 in StateTracker, and the protection for these cases in GeneralPloidyExactAFCalc which just wasn't right
-- Changed UG / HC to use this one via the StandardCallerArgumentCollection
-- Update the AFCalcFactory.Calculation to have a getDefault() value instead of having a duplicate entry in the enums
-- GeneralPloidyExactAFCalc turns -Infinity values into -Double.MAX_VALUE, so our calculations pass unit tests
-- Bugfix for GeneralPloidyGenotypeLikelihoodsCalculationModel, return a null VC when the only allele we get from our final alleles to use method is the reference base
-- Fix calculation of reference posteriors when P(AF == 0) = 0.0 and P(AF == 0) = X for some meaningful value of X. Added unit test to ensure this behavior is correct
-- Fix horrible sorting bug in IndependentAllelesDiploidExactAFCalc that applied the theta^N priors in the wrong order. Add contract to ensure this doesn't ever happen again
-- Bugfix in GLBasedSampleSelector, where VCs without any polymorphic alleles were being sent to the exact model
--
-- These two classes were really the same, and now they are actually the same!
-- Cleanuped the interfaces, removed duplicate data
-- Added lots of contracts, some of which found numerical issues with GeneralPloidyExactAFCalc (which have been patched over but not fixed)
-- Moved goodProbability and goodProbabilityVector utilities to MathUtils. Very useful for contracts!
Changed ReflectionUtils.getGenericTypes' order of looking for @ClassType since the primitive generic wasn't completely erased, only changed to Object which is incorrect.
More fixes to @Arguments labeled as java.io.File via incorrect @Input annotation.
Put in a default undocumented implementation of @Argument doc() to match the one added to @Input.
The CompressionStash is now responsible for keeping track of all intervals that must be kept uncompressed by all samples. In general this is a list generated by a tumor sample that will enforce all normal samples to abide.
- Updated ReduceReads integration tests
- Sliding Window is now using the CompressionStash (single sample).
DEV-104 #resolve #time 3m
-- Ensures that the posteriors remain within reasonable ranges. Fixed bug where normalization of posteriors = {-1e30, 0.0} => {-100000, 0.0} which isn't good. Now tests ensure that the normalization process preserves log10 precision where possible
-- Updated MathUtils to make this possible
-- Remove capability to truncate genotype likelihoods -- this wasn't used and isn't really useful after all
-- Added lots of contracts and docs, still more to come.
-- Created a default makeMaxLikelihoods function in ReferenceDiploidExactAFCalc and DiploidExactAFCalc so that multiple subclasses don't just do the default thing
-- Generalized reference bi-allelic model in IndependentAllelesDiploidExactAFCalc so that in principle any bi-allelic reference model can be used.
-- Fixed minor numerical stability issue in AFCalcResult
-- posterior of joint A/B/C is 1 - (1 - P(D | AF_b == 0)) x (1 - P(D | AF_c == 0)), for any number of alleles, obviously. Now computes the joint posterior like this, and then back-calculates likelihoods that generate these posteriors given the priors. It's not pretty but it's the best thing to do
-- Superceded by IndependentAFCalc
-- Added support to read in an ExactModelLog in AFCalcPerformanceTest and run the independent alleles model on it.
-- A few misc. bug fixes discovered during running the performance test
Added targets to build.xml to effectively 'mvn install' packaged GATK/Queue from ant.
TODO: Versions during 'mvn install' are hardcoded at 0.0.1 until a better versioning scheme that works with maven dependencies has been identified.
Modified the SAMFileWriterArgumentTypeDescriptor to accept output bam files that are null if they're not required (in the @Output annotation).
This change enables the nWayOut parameter for the IndeRealigner and ReduceReads to operate optionally while maintaining the original single way out.
[#DEV-10 transition:31 resolution:1]
-- Before this branch, the EXACT calculation implementation was largely based on historical choices in the UnifiedGenotyper. The code was badly organized, there were no unit tests, and the Diploid EXACT calculation was super slow O(n.samples ^ n.alt.alleles)
-- Reorganized code into a single class AFCalc superclass that carries out the calculation and an AFCalcResult object that contains only the information we should expose to code users, and is well-validated.
-- Implement a new model for the multi-allelic exact calculation that sweeps for each alt allele B all likelihoods into a bi-allelic model XB where X is all alleles != B, and calls these all separately using the reference bi-allelic model. It produces identical quals for the bi-allelic case but slightly different results for multi-allelics due to a genuine model difference in that this Independent model doesn't penalize fully all genotype configurations as occurs in the Reference multi-allelic implementation. However, it seems after much debate that the reference model is doing the wrong thing, so in fact the Independent model seems correct. This code isn't the default implementation yet, simply because I want to do some cleanup and discuss with the methods group before enabling.
-- Constrained search model implemented, but will be deleted in a subsequent code cleanup
-- Massive (40K) suite of unit tests the exact models, which are passing for the reference and the independent alleles exact model.
-- Restored -- but isn't 100% hooked up -- the original clean bi-allelic model for Ryan to pass his optimized logless version on.
-- The only way to create these AFCalc objects is through an AFCalcFactory, which again validates its arguments. The AFCalcFactory.Calculation enum exposes calculations to the UG / HC as the AFModel.
-- Separated AFCalc from UG, into its own package that could in principle be pushed into utils now
-- Created a simple main[] function to run performance tests of the EXACT model.
-- Updating integration tests, confirming that results for the original EXACT model are as expected given our new more rigorous application of likelihoods, priors, and posteriors
-- Fix basic logic bug in AFCalcResult.isPolymorphic and UnifiedGenotypeEngine, where isNonRef really meant isRef. Not ideal. Finally caught by some tests, but good god it almost made it into the code
-- Now takes the Math.abs of the phred-scaled confidence so that we don't see -0.0
-- Massive new suite of unit tests to ensure that bi-allelic and tri-allele events are called properly with all models, and that the IndependentAllelesDiploidExactAFCalc calls events with up to 4 alt alleles correctly. ID'd some of the bugs below
-- Fix sort order bug in IndependentAllelesDiploidExactAFCalc caught by new unit tests
-- Fix bug in GeneralPloidyExactAFCalc where the AFCalcResult has meaningless values in the likelihoods when no there we no informative GLs.
-- UnifiedGenotyperEngine uses only the alleles used in genotyping, not the original alleles, when considering which alleles to include in output
-- AFCalcFactory has a more informative info message when looking for and selecting an exact model to use in genotyping
-- New capabilities in IndependentAllelesDiploidExactAFCalc to actually apply correct theta^n.alt.allele prior.
-- Tests that theta^n.alt.alleles is being applied correctly
-- Bugfix: keep in logspace when computing posterior probability in toAFCalcResult in AFCalcResultTracker.java
-- Bugfix: use only the alleles used in genotyping when assessing if an allele is polymorphic in a sample in UnifiedGenotyperEngine
-- AFCalcFactory is the only way to make AFCalcs now. There's a nice ordered enum there describing the models and their ploidy and max alt allele restrictions. The factory makes it easy to create them, and to find models that work for you given your ploidy and max alt alleles.
-- AFCalc no longer has UAC constructor -- only AFCalcFactory does. Code cleanup throughout
-- Enabling more unit tests, all of which almost pass now (except for IndependentAllelesDiploidExactAFCalc which will be fixed next)
-- It's now possible to run the UG / HC with any of the exact models currently in the system.
-- Code cleanup throughout the system, reorganizing the unit tests in particular
-- Continuing to get IndependentAllelesDiploidExactAFCalc working correctly. A long way towards the right answer now, but still not there
-- Restored (but not tested) OriginalDiploidExactAFCalc, the clean diploid O(N) version for Ryan
-- MathUtils.normalizeFromLog10 no longer returns -Infinity when kept in log space, enforces the min log10 value there
-- New convenience method in VariantContext that looks up the allele index in the alleles
-- AFCalcResult now sports a isPolymorphic and getLog10PosteriorAFGt0ForAllele functions that allow you to ask individually whether specific alleles we've tried to genotype are polymorphic given some confidence threshold
-- Lots of contracts for AFCalcResult
-- Slowly killing off AFCalcResultsTracker
-- Fix for the way UG checks for alt alleles being polymorphic, which is now properly conditioned on the alt allele
-- Change in behavior for normalizeFromLog10 in MathUtils: now sets the log10 for 0 values to -10000, instead of -Infinity, since this is really better to ensure that we don't have -Infinity values traveling around the system
-- ExactAFCalculationModelUnitTest now checks for meaningful pNonRef values for each allele, uncovering a bug in the GeneralPloidy (not fixed, related to Eric's summation issue from long ago that was reverted) in that we get different results for diploid and general-ploidy == 2 models for multi-allelics.
-- All of the code now uses the AFCalc object, not the not package protected AFCalcResultTracker. Nearly all unit tests pass (expect for a contract failing one that will be dealt with in subsequent commit), due to -Infinity values from normalizeLog10.
-- Changed the way that UnifiedGenotyper decides if the best model is non-ref. Previously looked at the MAP AC, but the MAP AC values are no longer provided by AFCalcResult. This is on purpose, because the MAP isn't a meaningful quantity for the exact model (i.e., everything is going to go to MLE AC in some upcoming commit). If you want to understand why come talk to me. Now uses the isPolymorphic function and the EMIT confidence, so that if pNonRef > EMIT then the site is poly, otherwise it's mono.
-- Renamed old class AFCalcResultTracker. This object is now allocated by the AFCalc itself, since it is heavy-weight and was badly optimized in the UG with a thread-local variable. Now, since there's already a AFCalc thread-local there, we get that optimization for free.
-- Removed the interface to provide the AFCalcResultTracker to getlog10PNonRef.
-- Wrote new, clean but unused AFCalcResult object that will soon replace the tracker as the external interface to the AFCalc model results, leaving the tracker as an internal tracker structure. This will allow me to (1) finally test things exhaustively, as the contracts on this class are clear (2) finalize the IndependentAllelesDiploidExactAFCalc class as it can work with a meaningfully defined result across each object
-- This model separates each of N alt alleles, combines the genotype likelihoods into the X/X, X/N_i, and N_i/N_i biallelic case, and runs the exact model on each independently to handle the multi-allelic case. This is very fast, scaling at O(n.alt.alleles x n.samples)
-- Many outstanding TODOs in order to truly pass unit tests
-- Added proper unit tests for the pNonRef calculation, which all of the models pass
-- Now contained in a package called afcalc
-- Extracted standard alone classes from private static classes in ExactAF
-- Most fields are now private, with accessors
-- Overall cleaner organization now
-- Now there's no duplication between exact old and constrained models. The behavior is controlled by an overloaded abstract function
-- No more static function to access the linear exact model -- you have to create the surrounding class. Updated code in the system
-- Everything passes unit tests
-- walks over the genotypes in VC, and computes for each alt allele the maximum AC we need to consider in that alt allele dimension. Does the calculation based on the PLs in each genotype g, choosing to update the max AC for the alt alleles corresponding to that PL. Only takes the first lowest PL, if there are multiple genotype configurations with the same PL value. It takes values in the order of the alt alleles.
Validation of GenomeLocs in the FilePointer class was extremely inefficient
when the GenomeLocs were added one at a time rather than all at once.
Appears to mostly fix GSA-604
-- Right now the state of the AFCaclulationResult can be corrupt (ie, log10 likelihoods can be -Infinity). Forced me to disable reasonable contracts. Needs to be thought through
-- exactCallsLog should be optional
-- Update UG integration tests as the calculation of the normalized posteriors is done in a marginally different way so the output is rounded slightly differently.
-- UnifiedGenotyperEngine no longer keeps a thread local double[2] array for the normalized posteriors array. This is way heavy-weight compared to just making the array each time.
-- Added getNormalizedPosteriorOfAFGTZero and getNormalizedPosteriorOfAFzero to AFResult object. That's the place it should really live
-- Add tests for priors, uncovering bugs in the contracts of the tri-allelic priors w.r.t. the AC of the MAP. Added TODOs
-- AFResult now tracks the number of evaluations (turns through the model calculation) so we can now compute the scaling of exact model itself as a function of n samples
-- Added unittests for priors (flat and human)
-- Discovered nasty general ploidy bug (enabled with Guillermo_FIXME)
-- Added combinatorial unit tests for both Diploid and General (in diploid-case) for 2 and 3 alleles in all combinations of sample types (i.e., AA, AB, BB and equiv. for tri-allelic). More assert statements to ensure quality of the result.
-- Added docs (DOCUMENT YOUR CODE!) to AlleleFrequencyCalculationResult, with proper input error handling and contracts. Made mutation functions all protected
-- No longer need to call reset on your AlleleFrequencyCalculationResult -- it'd done for you in the calculation function. reset is a protected method now, so it's all cleaner and nicer this way
-- TODO still -- need to add edge-case tests for non-informative samples (0,0,0), for the impact of priors, and I need to add some way to test the result of the pNonRef
-- Added a true base class that only does truly common tasks (like manage call logging)
-- This base class provides the only public method (getLog10PNonRef) and calls into a protected compute function that's abstract
-- Split ExactAF into superclass ExactAF with common data structures and two subclasses: DiploidExact and GeneralPloidyExact
-- Added an abstract reduceScope function that manages the simplification of the input VariantContext in the case where there are too many alleles or other constraints require us to only attempt a smaller computation
-- All unit tests pass
-- This allows us to log all of the information about the exact model call (alleles, priors, PLs, result, and runtime) to a file for later debugging / optimization
1) GATKArgumentCollection has a command to turn off randomization if setting the seed isn't enough. Right now it's only hooked into RankSumTest.
2) RankSumTest now can be passed a boolean telling it whether to use a dithering or non-randomizing comparator. Unit tested.
3) VariantsToBinaryPed can now output in both individual-major and SNP-major mode. Integration test.
4) Updates to PlinkBed-handling python scripts and utilities.
5) Tool for calculating (LD-corrected) GRMs put under version control. This is analysis for T2D, but I don't want to lose it should something happen to my computer.
Sometimes the GATK engine creates a single monolithic FilePointer representing all regions
in all BAM files. In such cases, the monolithic FilePointer is the only FilePointer emitted
by the BAMScheduler, and it's safe to allow it to contain regions and intervals from multiple
contigs.
This fixes support for reading unindexed BAM files (since an unindexed BAM is one case
in which the engine creates a monolithic FilePointer).
Nasty, nasty bug -- if we were extremely unlucky with shard boundaries, we might
end up with a shard containing only unmapped mates of mapped reads. In this case,
ReadShard.getReadsSpan() would not behave correctly, since the shard as a whole would
be marked "mapped" (since it refers to mapped intervals) yet consist only of unmapped
mates of mapped reads located within those intervals.
1) ValidateVariants removed in favor of direct validation VariantContexts. Integration test added to test broken contexts.
2) Enabling indel and SV output. Still bi-allelic sites only. Integration tests added for these cases.
3) Found a bug where GQ recalculation (if a genotype has PLs but no GQ) would only happen for flipped encoding. Fixed. Integration test added.
Merge all FilePointers for each contig into a single, merged, optimized FilePointer
representing all regions to visit in all BAM files for a given contig.
This helps us in several ways:
-It allows us to create a single, persistent set of iterators for each contig,
finally and definitively eliminating all Shard/FilePointer boundary issues for
the new experimental ReadWalker downsampling
-We no longer need to track low-level file positions in the sharding system (which
was no longer possible anyway given the new experimental downsampling system)
-We no longer revisit BAM file chunks that we've visited in the past -- all BAM
file access is purely sequential
-We no longer need to constantly recreate our full chain of read iterators
There are also potential dangers:
-We hold more BAM index data in memory at once. Given that we merge and optimize
the index data during the merge, and only hold one contig's worth of data at a
time, this does not appear to be a major issue. TODO: confirm this!
-With a huge number of samples and intervals, the FilePointer merge operation
might become expensive. With the latest implementation, this does not
appear to be an issue even with a huge number of intervals (for one sample, at least),
but if it turns out to be a problem for > 1 sample there are things we can do.
Still TODO: unit tests for the new FilePointer.union() method
-- Fixes monster bug in the way that traversal engines interacted with the NanoScheduler via the output tracker.
-- ThreadLocalOutputTracker is now a ThreadBasedOutputTracker that associates via a map from a master thread -> the storage map. Lookups occur by walking through threads in the same thread group, not just the thread itself (TBD -- should have a map from ThreadGroup instead)
-- Removed unnecessary debug statement in GenomeLocParser
-- nt and nct officially work together now
TestNG skips tests when an exception occurs in a data provider,
which is what was happening here.
This was due to an AWFUL AWFUL use of a non-final static for
ReadShard.MAX_READS. This is fine if you assume only one instance
of SAMDataSource, but with multiple tests creating multiple SAMDataSources,
and each one overwriting ReadShard.MAX_READS, you have a recipe for
problems. As a result of this the test ran fine individually, but not as
part of the unit test suite.
Quick fix for now to get the tests running -- this "mutable static"
interface should really be refactored away though, when I have time.
It's now possible to run with experimental downsampling enabled
using the --enable_experimental_downsampling engine argument.
This is scheduled to become the GATK-wide default next week after
diff engine output for failing tests has been examined.
Notify all downsamplers in our pool of the current global genomic position every
DOWNSAMPLER_POSITIONAL_UPDATE_INTERVAL position changes, not every single
positional change after that threshold is first reached.
-Only used when experimental downsampling is enabled
-Persists read iterators across shards, creating a new set only when we've exhausted
the current BAM file region(s). This prevents the engine from revisiting regions discarded
by the downsamplers / filters, as could happen in the old implementation.
-SAMDataSource no longer tracks low-level file positions in experimental mode. Can strip
out all related code when the engine fork is collapsed.
-Defensive implementation that assumes BAM file regions coming out of the BAM Schedule
can overlap; should be able to improve performance if we can prove they cannot possibly
overlap.
-Tests a bit on the extreme side (~8 minute runtime) for now; will scale these back
once confidence in the code is gained
-- See https://jira.broadinstitute.org/browse/GSA-573
-- Uses InheritedThreadLocal storage so that children threads created by the NanoScheduler see the parent stubs in the main thread.
-- Added explicit integration test that checks that -nt 1, 2 and -nct 1, 2 give the same results for GLM BOTH with the UG over 1 MB.
Doesn't actually fix the problem, and adds an unnecessary delay in closing down NanoScheduler, so reverting.
This reverts commit 66b820bf94ae755a8a0c71ea16f4cae56fd3e852.
1) Better documentation on the meta data file for VariantsToBinaryPed with examples of each file type
2) MannWhitneyU can now take an argument on creation to turn off dithering. This pertains to JIRA-GSA-571 but does not fix it,
as it isn't hooked up to the command line. Next step is to add an argument to the command line where it's accessible to the
annotation classes (e.g. from either UG or the VariantAnnotator).
3) Added some dumb python scripts to deal with Plink files, and a script to convert plink binaries to VCF to help sanity check. Basically if you want to do an analysis on genotype data stored in plink binary format, your choices are:
1) Add a new module to Plink [difficulty rating: Impossible -- code obfuscation]
2) Steal plink parsing code from software (Plink/PlinkSeq/GCTA/Emacks/etc) that readds the files [difficulty rating: Oppressive -- code not modularized at all)
3) Write your own dumb stuff [difficutly rating: Annoying]
What's been added is the result of 3. It's a library so nobody else has to do this, so long as they're comfortable with python.
-- Renamed TraversalErrorManager to the more general MultiThreadedErrorTracker
-- ErrorTracker is now used throughout the NanoScheduler. In order to properly handle errors, the work previously done by main thread (submit jobs, block on reduce) is now handled in a separate thread. The main thread simply wakes up peroidically and checks whether the reduce result is available or if an error has occurred, and handles each appropriately.
-- EngineFeaturesIntegrationTest checks that -nt and -nct properly throw errors in Walkers
-- Added NanoSchedulerUnitTest for input errors
-- ThreadEfficiencyMonitoring is now disabled by default, and can be enabled with a GATK command line option. This is because the monitoring doesn't differentiate between threads that are supposed to do work, and those that are supposed to wait, and therefore gives misleading results.
-- Build.xml no longer copies the unittest results verbosely
-- Refactored error handling from HMS into utils.TraversalErrorManager, which is now used by HMS and will be usable by NanoScheduler
-- Generalized EngineFeaturesIntegrationTest to test map / reduce error throwing for nt 1, nt 2 and nct 2 (disabled)
-- Added unit tests for failing input iterator in NanoScheduler (fails)
-- Made ErrorThrowing NanoScheduable
-- V3 + V4 algorithm for NanoScheduler. The newer version uses 1 dedicated input thread and n - 1 map/reduce threads. These MapReduceJobs perform map and a greedy reduce. The main thread's only job is to shuttle inputs from the input producer thread, enqueueing MapReduce jobs for each one. We manage the number of map jobs now via a Semaphore instead of a BlockingQueue of fixed size.
-- This new algorithm should consume N00% CPU power for -nct N value.
-- Also a cleaner implementation in general
-- Vastly expanded unit tests
-- Deleted FutureValue and ReduceThread
-- For the pooled caller we were writing diploid no-calls even when other samples were haploid. Changed maxPloidy function to return a defaultPloidy, rather than 0, in the case where all samples are missing.
-- VCF/BCF Writers now create missing genotypes with the ploidy of other samples, or 2 if none are available at all.
-- Updating integration tests for general ploidy, as previously we wrote ./. even when other calls were 0/0/0/0/0/0/0/0/0/0/0/0/0/0/0/0/0/0/0/1/1/1/1/1, but now we write ./././././././././././././././././././././././. (ugly but correct)
-- Previous code was looking for a -1 result from maxPloidy() but the result as actually 0, so instead of writing a diploid no call we were actually writing "unavailable" genotypes, and failing the BCF == VCF test in integration tests. Fixed.
-- Turns out this was consuming 30% of the UG runtime, and causing problems elsewhere.
-- Removed addMissingSamples from VariantcontextUtils, and calls to it
-- Updated VCF / BCF writers to automatically write out a diploid no call for missing samples
-- Added unit tests for this behavior in VariantContextWritersUnitTest
1) SelectVariants could throw a ReviewedStingException (one of the nasty "Bug:") ones if the user requested a sample that wasn't present in the VCF. The walker now
checks for this in the initialize() phase, and throws a more informative error if the situation is detected. If the user simply wants to subset the VCF to
all the samples requested that are actually present in the VCF, the --ALLOW_NONOVERLAPPING_COMMAND_LINE_SAMPLES flag changes this UserException to a Warning,
and does the appropriate subsetting. Added integration tests for this.
2) GenotypeLikelihoods has an unsafe method getLog10GQ(GenotypeType), which is completely broken for multi-allelic sites. I marked that method
as deprecated, and added methods that use the context of the allele ordering (either directly specified or as a VC) to retrieve the appropriate GQ, and
added a unit test to cover this case. VariantsToBinaryPed needs to dynamically calculate the GQ field sometimes (because I have some VCFs with PLs but no GQ).
-- Now prints out a single combined NanoScheduler runtime profile report across all nano schedulers in use. So now if you run with -nt 4 you'll get one combined NanoScheduler profiler across all 4 instances of the NanoScheduler within TraverseXNano.
-- Basically you cannot safely use instance specific ThreadLocal variables, as these cannot be safely cleaned up. The old implementation kept pointers to old writers, with huge tribble block indexes, and eventually we crashed out of integration tests
-- See http://weblogs.java.net/blog/jjviana/archive/2010/06/10/threadlocal-thread-pool-bad-idea-or-dealing-apparent-glassfish-memor for more information
-- New implementation uses a borrow/return schedule with a list of N TraversalEngines managed by the MicroScheduler directly.
-- Can now say -nt 4 and -nct 4 to get 16 threads running for you!
-- TraversalEngines are now ThreadLocal variables in the MicroScheduler.
-- Misc. code cleanup, final variables, some contracts.
-- TraversalProgressMeter now completely generalized, named ProgressMeter in utils.progressmeter. Now just takes "nRecordsProcessed" as an argument to print reads. Completely removes dependence on complex data structures from TraversalProgressMeter. Can be used to measure progress on any task with processing units in genomic locations.
-- a fairly simple, class with no dependency on GATK engine or other features.
-- Currently only used by the TraversalEngine / MicroScheduler but could be used for any purpose now, really.
-- Previously these core progress metering functions were all in TraversalEngine, and available to subclasses like TraverseLoci via inheritance. The problem here is that the upcoming data threads x cpu threads parallelism requires one master copy of the progress metering shared among all traversals, but multiple instantiations of traverse engines themselves.
-- Because the progress metering code has horrible anyway, I've refactored and vastly cleaned up and simplified all of these capabilities into TraversalProgressMeter class. I've simplified down the classes it uses to work (STILL SOME TODOs in there) so that it doesn't reach into the core GATK engine all the time. It should be possible to write some nice tests for it now. By making it its own class, it can protect itself from multi-threaded access with a single synchronized printProgress function instead of carrying around multiple lock objects as before
-- Cleaned up the start up of the progress meter. It's now handled when the meter is created, so each micro scheduler doesn't have to deal with proper initialization timing any longer
-- Simplified and made clear the interface for shutting down the traversal engines. There's no a shutdown method in TraversalEngine that's called once by the MicroScheduler when the entire traversing in over. Nano traversals now properly shut down (was subtle bug I undercovered here). The printing of on traversal done metering is now handled by MicroScheduler
-- The MicroScheduler holds the single master copy of the progress meter, and doles it out to the TraversalEngines (currently 1 but in future commit there will be N).
-- Added a nice function to GenomeAnalysisEngine that returns the regions we will be processing, either the intervals requested or the whole genome. Useful for progress meter but also probably for other infrastructure as well
-- Remove a lot of the sh*ting Bean interface getting and setting in MicroScheduler that's no longer useful. The generic bean is just a shell interface with nothing in it.
-- By removing a lot of these bean accessors and setters many things are now final that used to be dynamic.
This will prevent bugs from occurring when Vanilla make changes to the API
as described here: http://vanillaforums.com/blog/api#configuration
Based on the bug that broke the website Guide section on 9/6/12,
the GATKDocs posting system will probably break in the next release if
this is not applied as a bug fix.
-- I've rewritten the entire NS framework to use a producer / consumer model for input -> map and from map -> reduce. This is allowing us to scale reasonably efficiently up to 4 threads (see figure). Future work on the nano scheduler will be itemized in a separate JIRA entry.
-- Restructured the NS code for clarity. Docs everywhere.
-- This is considered version 1.0
-Off by default; engine fork isolates new code paths from old code paths,
so no integration tests change yet
-Experimental implementation is currently BROKEN due to a serious issue
involving file spans. No one can/should use the experimental features
until I've patched this issue.
-There are temporarily two independent versions of LocusIteratorByState.
Anyone changing one version should port the change to the other (if possible),
and anyone adding unit tests for one version should add the same unit tests
for the other (again, if possible). This situation will hopefully be extremely
temporary, and last only until the experimental implementation is proven.
-- The NanoScheduler is doing a good job at tracking important information like time spent in map/reduce/input etc.
-- Can be disabled with static boolean in MicroScheduler if we have problems
-- See GSA-515 Nanoscheduler GSA-549 Retire TraverseReads and TraverseLoci after testing confirms nano scheduler version in single threaded version is fine
-- Closes GSA-515 Nanoscheduler GSA-542 Good interface to nanoScheduler
-- Old -nt means dataThreads
-- New -cnt (--num_cpu_threads_per_data_thread) gives you n cpu threads for each data thread in the system
-- Cleanup logic for handling data and cpu threading in HMS, LMS, and MS
-- GATKRunReport reports the total number of threads in use by the GATK, not just the nt value
-- Removed the io,cpu tags for nt. Stupid system if you ask me. Cleaned up the GenomeAnalysisEngine and ThreadAllocation handling to be totally straightforward now
-- Separate updating cumulative traversal metrics from printing progress. There's now an updateCumulativeMetrics function and a printProgress() that only takes a current position
-- printProgress now soles relies on the time since the last progress to decide if it will print or not. No longer uses the number of cycles, since this isn't reliable in the case of nano scheduling
-- GenomeAnalysisEngine now maintains a pointer to the master cumulative metrics. getCumulativeMetrics never returns null, which was handled in some parts of the code but not others.
-- Update all of the traversals to use the new updateCumulativeMetrics, printProgress model
-- Added progress callback to nano scheduler. Every bufferSize elements this callback is invoked, allowing us to smoothly update the progress meter in the NanoScheduler
-- Rename MapFunction to NanoSchedulerMap and the same for reduce.
-- Refactored TraverseLoci into old linear version and nano scheduling version
-- Temp. GATK argument to say how many nano threads to use
-- Can efficiently scale to 3 threads before blocking on input
-- Instead of returning directly the result of map(), returns a MapResult object with the value and a reduceMe flag.
-- Reduce function respects the reduceMe flag
-- Code cleanup and more documentation
-- Helpful for understanding where the time goes to each bit of the code.
-- Controlled by a local static boolean, to avoid the potential overhead in general
-- TraverseReadsNano prints progress at the end of each traversal unit
-- Fix bugs in TraversalEngine printProgress
-- Synchronize the method so we don't get multiple logged outputs when two or more HMSs call printProgress before initialization at the start!
-- Fix the logic for mustPrint, which actually had the logic of mustNotPrint. Now we see the done log line that was always supposed to be there
-- Fix output formatting, as the done() line was incorrectly shifting over the % complete by 1 char as 100.0% didn't fit in %4.1f
-- Add clearer doc on -PF argument so that people know that the performance log can be generated to standard out if one wants
- VariantAnnotatorEngine changed to call genotype annotations even if pilups and allele -> likelihood mappings are not present. Current genotype annotations altered to check for null pilupes and null mappings.
-- In the process uncovered two strange things
1 -- qualityScoreByFullCovariateKey was created but never used. Seems like a cache?
2 -- Discovered nasty bug in BaseRecalibrator: https://jira.broadinstitute.org/browse/GSA-534
-- These are like read filters but can be applied either on input, on output, of handled by the walker
-- Previous example of BAQ now uses the general framework
-- Resulted in massive conceptual cleanup of SAMDataSource and ReadProperties! Yeah!
-- BQSR now uses this framework. We can now do BQSR on input, on output, or within a walker
-- PrintReads now handles all read transformers in the walker in map, enabling us to parallelize PrintReads with BAQ and BQSR
-- Currently BQSR is excepting in parallel, which subsequent commit with fix
-- Removed global variable setting in GenomeAnalysisEngine for BAQ, as command line parameters are cleanly handled by ReadTransformer infrastructure
-- In principle ReadFilters are just a special kind of ReadTransformer, but this refactoring is larger than I can do. It's a JIRA entry
-- Many files touched simply due to the refactoring and renaming of classes
-- A higher level interface to declare parallelism capability of a walker. This interface means that the walker can be multi-threaded, but doesn't necessarily support TreeReducible interface, which forces you to have a combine ReduceType operation that isn't appropriate for parallel read walkers
-- Updated ReadWalkers to implement ThreadSafeMapReduce not TreeReducible
-- TraverseReadsNano modified to read in all input data before invoking maps, so the input to TraverseReadsNano is a MapData object holding the sam record, the ref context, and the refmetadatatracker.
-- Update ValidateRODForReads to be tree reducible, using synchronized map and explicitly sort the output map from locations -> counts in onTraversalDone
-- Expanded integration tests to test nt 1, 2, 4.
-- Yes, GenomeLoc.compareTo was broken. The compareTo function only considered the contig and start position, but not the stop, when comparing genome locs.
-- Updated GenomeLoc.compareTo function to account for stop. Updated GATK code where necessary to fix resulting problems that depended on this.
-- Added unit tests to ensure that hashcode, equals, and compareTo are all correct for GenomeLocs
In addition, fix for GSA-310. If supplied -rf argument does not match a known read filter, the list of read filters will be printed, and users directed to the documentation for more information.
-- Previous behavior was unnecessary and causes all sorts of problems with RODs for reads. The old implementation simply failed in this case. The new code handles this correctly by forcing shards to have all of their data on a single contig.
-- Added a PrintReads integration test to ensure this behavior is correct
-- Adding test BAMs that have < 200 reads and span across contig boundaries
-- shardSpan is only calculated when there some ROD is live in the GATK. No sense in paying the cost per read when you don't need it
-- Update contract to allow null span or unmapped span (good catch unittests!)
-- Deleted ReadMetaDataTracker
-- Added function to ReadShard to give us the span from the left most position of the reads in the shard to the right most, which is needed for the new view
-- ReadMetaDataTracker is dead! Long live the RefMetaDataTracker. Read walkers will soon just take RefMetaDataTracker objects. In this commit they take a class that trivially extends them
-- Rewrote ReadBasedReferenceOrderedView to produce RefMetaDataTrackers not the old class.
-- This new implementation produces thread-safe objects (i.e., holds no points to shared state). Suitable for use (to be tested) with nano scheduling
-- Simplified interfaces to use the simplest data structures (PeekableIterator) not the LocusAwareSeekableIterator, since I both hate those classes and this is on the long term trajectory to remove those from the GATK entirely.
-- Massively expanded DataProvider unit tests for ReadBasedReferenceOrderedView
-- Note that the old implementation of offset -> ROD in ReadRefMetaDataTracker was broken for any read not completely matching the reference. Rather than provide broken code the ReadMetaDataTracker only provides a "bag of RODs" interface. If you want to work with the relationship between the read and the RODs in your tool you need to manage the CIGAR element itself.
-- This commit breaks the new read walker BQSR, but Ryan knows this is coming
-- Subsequent commit will be retiring / fixing ValidateRODForReads
Reverting back to the original implementation, but now including write N's and write Q0's due to walkers that look at the same read multiple times in different reference windows
-- Old way (filtering for Q > 17 bases) resulted in biased FS when the site was good but there was a
systematic shift in the QUAL of REF and ALT between strands of the reads (sometimes happens)
-- New way (taking all bases) was consistent with BaseQualRankSum and other tests, but there can be
a lot of low qual reference bases on one strand in some techs (ION/PROTON/PACBIO) because of the
preference for introducing an indel vs. a mismatch.
-- This implementation allows us to have our cake and eat it to by computing both p-values, and
taking the maximum one (i.e., least significant).
-- No integration tests updated yet -- still exploring the consequences of this change
Eric Banks
Ryan Poplin
Mauricio Carneiro
Menachem Fromer
Mark DePristo
Joel Thibault
Ami Levy-Moonshine
Guillermo del Angel
kshakir
Andrey Sivachenko
David Roazen
Christopher Hartl
Yossi Farjoun
Geraldine Van der Auwera