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TRON-Bioinformatics/vafator: vafator v3.0.0

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vafator 3.0.0 Performance ~13x runtime improvement over v2 on a 292K variant VCF (SEQC2 WES WES_EA_1, 5.5 hours → 23 minutes with 4 cores). Streaming pileup iterator — replaced per-variant bam.pileup() calls with a single pileup iterator per chromosome per BAM. This eliminates the dominant source of overhead (repeated pysam pileup object construction and destruction) and reduces runtime ~4.4x on its own. Power calculation caching — _calculate_k and calculate_expected_vaf results are now cached per depth value and per (sample, chrom, pos) respectively, avoiding redundant scipy.stats.binom calls across variants with identical coverage. Rank sum test early exit — calculate_rank_sum_test now returns nan immediately when either distribution is empty, skipping unnecessary scipy.stats.ranksums calls. Chromosome-level parallelization — added --num-processes flag to distribute chromosomes across worker processes using ProcessPoolExecutor. Each worker opens its own BAM readers independently, avoiding shared state issues. Python upgrade Python upgraded to 3.11 pysam pinned to ==0.21.0 — versions 0.22+ have a regression where query_qualities returns incorrect values. Breaking changes --include-ambiguous-bases renamed to --exclude-ambiguous-bases — ambiguous bases (N and all IUPAC codes) are now included in depth of coverage by default. To restore the old behaviour of excluding them, pass --exclude-ambiguous-bases. This flag is inverted from the previous version. Zero-coverage variants — _bq, _mq, _pos annotations for variants with zero coverage previously reported nan; they now report 0.0. This affects a small number of variants (9/292,009 in the tested VCF). Additional features Random seed added to multiallelic filter CRAM support added Code quality VafatorVariant replaced by VariantRecord — the test utility class VafatorVariant (from vafator.tests.utils) is now a thin factory function returning a VariantRecord. Async VCF writing removed — the @background / asyncio / time.sleep(2) writing pattern was causing missing variants in the output. Replaced with synchronous batch writing. Type hints and docstrings added throughout annotator.py, pileups.py, and pileup_utils.py.

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