def main(args):
hl.init(default_reference='GRCh38')
logger = logging.getLogger("gnomad_qc.v3.load_data.compute_coverage")
if args.compute_coverage_ht:
print("Building reference context HT")
ref_ht = get_reference_ht(hl.get_reference('GRCh38'),
excluded_intervals=telomeres_and_centromeres.
ht().interval.collect())
ref_ht = ref_ht.checkpoint("gs://gnomad-tmp/ref_context.ht",
overwrite=True)
logger.info("Done building reference context HT")
mt = get_gnomad_v3_mt()
mt = mt.filter_cols(meta.ht()[mt.col_key].release)
coverage_ht = compute_coverage_stats(mt, ref_ht)
coverage_ht = coverage_ht.checkpoint(
'gs://gnomad-tmp/gnomad.genomes_v3.coverage.summary.ht',
overwrite=True)
coverage_ht = coverage_ht.naive_coalesce(5000)
coverage_ht.write(coverage('genomes').versions['3.0'].path,
overwrite=args.overwrite)
if args.export_coverage:
ht = coverage('genomes').versions['3.0'].ht()
if 'count_array' in ht.row_value: # Note that count_array isn't computed any more, so this is v3.0-specific
ht = ht.drop('count_array')
ht.export(coverage_tsv_path('genomes', '3.0'))
def run_vep() -> hl.Table:
def get_mt_partitions(mt_path: str) -> List[hl.Interval]:
"""
This function loads the partitioning from a given MT.
Note that because it relies on hardcoded paths within the MT that are still in flux,
it isn't guaranteed to work on future versions of the MT format.
:param str mt_path: MT path
:return: MT partitions
:rtype: List of Interval
"""
logger.info(f'Reading partitions for {mt_path}')
import json
from os import path
mt = hl.read_matrix_table(mt_path)
with hl.hadoop_open(
path.join(mt_path, 'rows', 'rows', 'metadata.json.gz')) as f:
intervals_json = json.load(f)['jRangeBounds']
return hl.tarray(hl.tinterval(hl.tstruct(
locus=mt.locus.dtype)))._convert_from_json(intervals_json)
ht = get_gnomad_v3_mt(key_by_locus_and_alleles=True).rows()
ht = ht.filter(hl.len(ht.alleles) > 1)
return vep_or_lookup_vep(ht, reference='GRCh38')
def run_mendel_errors() -> hl.Table:
meta_ht = meta.ht()
ped = pedigree.versions["raw"].pedigree()
logger.info(f"Running Mendel errors for {len(ped.trios)} trios.")
fake_ped = create_fake_pedigree(
n=100,
sample_list=list(
meta_ht.aggregate(
hl.agg.filter(
hl.rand_bool(0.01)
& ((hl.len(meta_ht.qc_metrics_filters) == 0)
& hl.or_else(hl.len(meta_ht.hard_filters) == 0, False)),
hl.agg.collect_as_set(meta_ht.s),
))),
real_pedigree=ped,
)
merged_ped = hl.Pedigree(trios=ped.trios + fake_ped.trios)
ped_samples = hl.literal(
set([
s for trio in merged_ped.trios
for s in [trio.s, trio.pat_id, trio.mat_id]
]))
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True)
mt = mt.filter_cols(ped_samples.contains(mt.s))
mt = hl.filter_intervals(
mt, [hl.parse_locus_interval("chr20", reference_genome='GRCh38')])
mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
mt = mt.select_entries("GT", "END")
mt = hl.experimental.densify(mt)
mt = mt.filter_rows(hl.len(mt.alleles) == 2)
mendel_errors, _, _, _ = hl.mendel_errors(mt["GT"], merged_ped)
return mendel_errors
def compute_info() -> hl.Table:
"""
Computes a HT with the typical GATK AS and site-level info fields
as well as ACs and lowqual fields.
Note that this table doesn't split multi-allelic sites.
:return: Table with info fields
:rtype: Table
"""
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True,
remove_hard_filtered_samples=False)
mt = mt.filter_rows((hl.len(mt.alleles) > 1))
mt = mt.transmute_entries(**mt.gvcf_info)
# Compute AS and site level info expr
# Note that production defaults have changed:
# For new releases, the `RAWMQ_andDP` field replaces the `RAW_MQ` and `MQ_DP` fields
info_expr = get_site_info_expr(
mt,
sum_agg_fields=INFO_SUM_AGG_FIELDS + ['RAW_MQ'],
int32_sum_agg_fields=INFO_INT32_SUM_AGG_FIELDS + ['MQ_DP'],
array_sum_agg_fields=['SB'])
info_expr = info_expr.annotate(
**get_as_info_expr(mt,
sum_agg_fields=INFO_SUM_AGG_FIELDS + ['RAW_MQ'],
int32_sum_agg_fields=INFO_INT32_SUM_AGG_FIELDS +
['MQ_DP'],
array_sum_agg_fields=['SB']))
# Add AC and AC_raw:
# First compute ACs for each non-ref allele, grouped by adj
grp_ac_expr = hl.agg.array_agg(
lambda ai: hl.agg.filter(
mt.LA.contains(ai),
hl.agg.group_by(
get_adj_expr(mt.LGT, mt.GQ, mt.DP, mt.LAD),
hl.agg.sum(
mt.LGT.one_hot_alleles(mt.LA.map(lambda x: hl.str(x)))[
mt.LA.index(ai)]))), hl.range(1, hl.len(mt.alleles)))
# Then, for each non-ref allele, compute
# AC as the adj group
# AC_raw as the sum of adj and non-adj groups
info_expr = info_expr.annotate(
AC_raw=grp_ac_expr.map(
lambda i: hl.int32(i.get(True, 0) + i.get(False, 0))),
AC=grp_ac_expr.map(lambda i: hl.int32(i.get(True, 0))))
info_ht = mt.select_rows(info=info_expr).rows()
# Add lowqual flag
info_ht = info_ht.annotate(lowqual=get_lowqual_expr(
info_ht.alleles,
info_ht.info.QUALapprox,
# The indel het prior used for gnomad v3 was 1/10k bases (phred=40).
# This value is usually 1/8k bases (phred=39).
indel_phred_het_prior=40))
return info_ht.naive_coalesce(5000)
def main(args):
hl.init(log='/frequency_data_generation.log', default_reference='GRCh38')
logger.info("Reading sparse MT and metadata table...")
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True)
meta_ht = meta.ht().select('pop', 'sex', 'project_id', 'release', 'sample_filters')
if args.test:
logger.info("Filtering to chr20:1-1000000")
mt = hl.filter_intervals(mt, [hl.parse_locus_interval('chr20:1-1000000')])
mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
logger.info("Annotating sparse MT with metadata...")
mt = mt.annotate_cols(meta=meta_ht[mt.s])
mt = mt.filter_cols(mt.meta.release)
samples = mt.count_cols()
logger.info(f"Running frequency table prep and generation pipeline on {samples} samples")
logger.info("Computing adj and sex adjusted genotypes.")
mt = mt.annotate_entries(
GT=adjusted_sex_ploidy_expr(mt.locus, mt.GT, mt.meta.sex),
adj=get_adj_expr(mt.GT, mt.GQ, mt.DP, mt.AD)
)
logger.info("Densify-ing...")
mt = hl.experimental.densify(mt)
mt = mt.filter_rows(hl.len(mt.alleles) > 1)
logger.info("Generating frequency data...")
mt = annotate_freq(
mt,
sex_expr=mt.meta.sex,
pop_expr=mt.meta.pop
)
# Select freq, FAF and popmax
faf, faf_meta = faf_expr(mt.freq, mt.freq_meta, mt.locus, POPS_TO_REMOVE_FOR_POPMAX)
mt = mt.select_rows(
'freq',
faf=faf,
popmax=pop_max_expr(mt.freq, mt.freq_meta, POPS_TO_REMOVE_FOR_POPMAX)
)
mt = mt.annotate_globals(faf_meta=faf_meta)
# Annotate quality metrics histograms, as these also require densifying
mt = mt.annotate_rows(
**qual_hist_expr(mt.GT, mt.GQ, mt.DP, mt.AD)
)
logger.info("Writing out frequency data...")
if args.test:
mt.rows().write("gs://gnomad-tmp/gnomad_freq/chr20_1_1000000_freq.ht", overwrite=True)
else:
mt.rows().write(freq.path, overwrite=args.overwrite)
def main(args):
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True)
mt = mt.annotate_entries(
gvcf_info=mt.gvcf_info.drop('ClippingRankSum', 'ReadPosRankSum'))
mt = mt.annotate_rows(
n_unsplit_alleles=hl.len(mt.alleles),
mixed_site=(hl.len(mt.alleles) > 2)
& hl.any(lambda a: hl.is_indel(mt.alleles[0], a), mt.alleles[1:])
& hl.any(lambda a: hl.is_snp(mt.alleles[0], a), mt.alleles[1:]))
mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
mt.write(args.split_mt_location, overwrite=args.overwrite)
def compute_stats(stats_path: str):
mt = get_gnomad_v3_mt()
mt = mt.filter_entries(hl.is_defined(mt.END))
ref_block_stats = mt.aggregate_entries(
hl.struct(ref_block_stats=hl.struct(
stats=hl.agg.stats(mt.END - mt.locus.position),
hist=hl.agg.hist(mt.END - mt.locus.position, 0, 9999, 10000),
hist_log=hl.agg.hist(hl.log10(1 + mt.END - mt.locus.position), 0,
5, 100)),
adj_ref_block_stats=hl.agg.filter(
get_adj_expr(mt.LGT, mt.GQ, mt.DP, mt.LAD),
hl.struct(stats=hl.agg.stats(mt.END - mt.locus.position),
hist=hl.agg.hist(mt.END - mt.locus.position, 0,
9999, 10000),
hist_log=hl.agg.hist(
hl.log10(1 + mt.END - mt.locus.position),
0, 5, 100)))))
with hl.hadoop_open(stats_path, 'wb') as f:
pickle.dump(ref_block_stats, f)
def main(args):
hl.init(default_reference='GRCh38')
coverage_version = args.coverage_version if args.coverage_version else CURRENT_GENOME_COVERAGE_RELEASE
logger = logging.getLogger("gnomad_qc.v3.load_data.compute_coverage")
logger.warning(
"Last time this was run (July 2020), this script required high-mem machines."
)
if args.compute_coverage_ht:
print("Building reference context HT")
ref_ht = get_reference_ht(
hl.get_reference('GRCh38'),
contigs=[f'chr{x}' for x in range(1, 23)] + ['chrX', 'chrY'],
excluded_intervals=telomeres_and_centromeres.ht().interval.collect(
))
ref_ht = ref_ht.checkpoint("gs://gnomad-tmp/ref_context.ht",
overwrite=True)
logger.info("Done building reference context HT")
mt = get_gnomad_v3_mt()
mt = mt.filter_cols(meta.ht()[mt.col_key].release)
coverage_ht = compute_coverage_stats(mt, ref_ht)
coverage_ht = coverage_ht.checkpoint(
'gs://gnomad-tmp/gnomad.genomes_v3.coverage.summary.ht',
overwrite=True)
coverage_ht = coverage_ht.naive_coalesce(5000)
coverage_ht.write(coverage('genomes').versions[coverage_version].path,
overwrite=args.overwrite)
if args.export_coverage:
ht = coverage('genomes').versions[coverage_version].ht()
if 'count_array' in ht.row_value: # Note that count_array isn't computed any more, so this is v3.0-specific
ht = ht.drop('count_array')
ht.export(coverage_tsv_path('genomes', coverage_version))
def main(args):
hl.init(default_reference='GRCh38', log='/qc_annotations.log')
if args.compute_info:
compute_info().write(get_info(split=False).path,
overwrite=args.overwrite)
if args.split_info:
split_info().write(get_info(split=True).path, overwrite=args.overwrite)
if args.export_info_vcf:
info_ht = get_info(split=False).ht()
hl.export_vcf(ht_to_vcf_mt(info_ht), info_vcf_path)
# if args.generate_ac: # TODO: compute AC and qc_AC as part of compute_info
# mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True, samples_meta=True)
# mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
#
# ht = generate_ac(mt, ).checkpoint('gs://gnomad-tmp/v3_ac_tmp.ht', overwrite=args.overwrite, _read_if_exists=not args.overwrite)
# ht.repartition(10000, shuffle=False).write(ac_ht_path, overwrite=args.overwrite)
if args.generate_fam_stats:
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True, samples_meta=True)
mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
fam_stats_ht = generate_fam_stats(mt, trios.path)
fam_stats_ht = fam_stats_ht.checkpoint(
'gs://gnomad-tmp/v3_fam_stats_tmp.ht',
overwrite=args.overwrite,
_read_if_exists=not args.overwrite)
fam_stats_ht = fam_stats_ht.repartition(10000, shuffle=False)
fam_stats_ht.write(fam_stats.path, overwrite=args.overwrite)
if args.export_transmitted_singletons_vcf:
export_transmitted_singletons_vcf()
if args.vep:
run_vep().write(vep.path, overwrite=args.overwrite)
def main(args):
hl.init(log="/variant_qc_evaluation.log")
if args.create_bin_ht:
create_bin_ht(
args.model_id,
args.n_bins,
).write(
get_score_bins(args.model_id, aggregated=False).path,
overwrite=args.overwrite,
)
if args.run_sanity_checks:
ht = get_score_bins(args.model_id, aggregated=False).ht()
logger.info("Running sanity checks...")
print(
ht.aggregate(
hl.struct(
was_biallelic=hl.agg.counter(~ht.was_split),
has_biallelic_rank=hl.agg.counter(
hl.is_defined(ht.biallelic_bin)),
was_singleton=hl.agg.counter(ht.singleton),
has_singleton_rank=hl.agg.counter(
hl.is_defined(ht.singleton_bin)),
was_biallelic_singleton=hl.agg.counter(ht.singleton
& ~ht.was_split),
has_biallelic_singleton_rank=hl.agg.counter(
hl.is_defined(ht.biallelic_singleton_bin)),
)))
if args.create_aggregated_bin_ht:
logger.warning(
"Use only workers, it typically crashes with preemptibles")
create_aggregated_bin_ht(args.model_id).write(
get_score_bins(args.model_id, aggregated=True).path,
overwrite=args.overwrite,
)
if args.extract_truth_samples:
logger.info(f"Extracting truth samples from MT...")
mt = get_gnomad_v3_mt(key_by_locus_and_alleles=True,
remove_hard_filtered_samples=False)
mt = mt.filter_cols(
hl.literal([v["s"]
for k, v in TRUTH_SAMPLES.items()]).contains(mt.s))
mt = hl.experimental.sparse_split_multi(mt, filter_changed_loci=True)
# Checkpoint to prevent needing to go through the large table a second time
mt = mt.checkpoint(
get_checkpoint_path("truth_samples", mt=True),
overwrite=args.overwrite,
)
for truth_sample in TRUTH_SAMPLES:
truth_sample_mt = mt.filter_cols(
mt.s == TRUTH_SAMPLES[truth_sample]["s"])
# Filter to variants in truth data
truth_sample_mt = truth_sample_mt.filter_rows(
hl.agg.any(truth_sample_mt.GT.is_non_ref()))
truth_sample_mt.naive_coalesce(args.n_partitions).write(
get_callset_truth_data(truth_sample).path,
overwrite=args.overwrite,
)
if args.merge_with_truth_data:
for truth_sample in TRUTH_SAMPLES:
logger.info(
f"Creating a merged table with callset truth sample and truth data for {truth_sample}..."
)
# Load truth data
mt = get_callset_truth_data(truth_sample).mt()
truth_hc_intervals = TRUTH_SAMPLES[truth_sample][
"hc_intervals"].ht()
truth_mt = TRUTH_SAMPLES[truth_sample]["truth_mt"].mt()
truth_mt = truth_mt.key_cols_by(
s=hl.str(TRUTH_SAMPLES[truth_sample]["s"]))
# Remove low quality sites
info_ht = get_info(split=True).ht()
mt = mt.filter_rows(~info_ht[mt.row_key].AS_lowqual)
ht = create_truth_sample_ht(mt, truth_mt, truth_hc_intervals)
ht.write(
get_callset_truth_data(truth_sample, mt=False).path,
overwrite=args.overwrite,
)
if args.bin_truth_sample_concordance:
for truth_sample in TRUTH_SAMPLES:
logger.info(
f"Creating binned concordance table for {truth_sample} for model {args.model_id}"
)
ht = get_callset_truth_data(truth_sample, mt=False).ht()
info_ht = get_info(split=True).ht()
ht = ht.filter(
~info_ht[ht.key].AS_lowqual
& ~hl.is_defined(telomeres_and_centromeres.ht()[ht.locus]))
logger.info("Filtering out low confidence regions and segdups...")
ht = filter_low_conf_regions(
ht,
filter_lcr=True,
# TODO: Uncomment when we have decoy path
filter_decoy=False, # True,
filter_segdup=True,
)
logger.info(
"Loading HT containing RF or VQSR scores annotated with a bin based on the rank of score..."
)
metric_ht = get_score_bins(args.model_id, aggregated=False).ht()
ht = ht.filter(hl.is_defined(metric_ht[ht.key]))
ht = ht.annotate(score=metric_ht[ht.key].score)
ht = compute_binned_truth_sample_concordance(
ht, metric_ht, args.n_bins)
ht.write(
get_binned_concordance(args.model_id, truth_sample).path,
overwrite=args.overwrite,
)
import hail as hl
from gnomad_qc.v3.resources import get_gnomad_v3_mt, last_END_position
# END RESOURCES
mt = get_gnomad_v3_mt()
mt = mt.select_entries('END')
t = mt._localize_entries('__entries', '__cols')
t = t.select(last_END_position=hl.or_else(
hl.min(
hl.scan.array_agg(
lambda entry: hl.scan._prev_nonnull(
hl.or_missing(hl.is_defined(entry.END),
hl.tuple([t.locus, entry.END]))), t.__entries).
map(lambda x: hl.or_missing((x[1] >= t.locus.position) & (x[
0].contig == t.locus.contig), x[0].position))), t.locus.position))
t.write(last_END_position.path, overwrite=True)
