-- 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.
-- 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.
-- 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
Ryan Poplin
Mark DePristo
Guillermo del Angel
Eric Banks
Yossi Farjoun