def test_de_novo(self):
mt = hl.import_vcf(resource('denovo.vcf'))
mt = mt.filter_rows(mt.locus.in_y_par(), keep=False) # de_novo_finder doesn't know about y PAR
ped = hl.Pedigree.read(resource('denovo.fam'))
r = hl.de_novo(mt, ped, mt.info.ESP)
r = r.select(
prior=r.prior,
kid_id=r.proband.s,
dad_id=r.father.s,
mom_id=r.mother.s,
p_de_novo=r.p_de_novo,
confidence=r.confidence).key_by('locus', 'alleles', 'kid_id', 'dad_id', 'mom_id')
truth = hl.import_table(resource('denovo.out'), impute=True, comment='#')
truth = truth.select(
locus=hl.locus(truth['Chr'], truth['Pos']),
alleles=[truth['Ref'], truth['Alt']],
kid_id=truth['Child_ID'],
dad_id=truth['Dad_ID'],
mom_id=truth['Mom_ID'],
p_de_novo=truth['Prob_dn'],
confidence=truth['Validation_Likelihood'].split('_')[0]).key_by('locus', 'alleles', 'kid_id', 'dad_id',
'mom_id')
j = r.join(truth, how='outer')
self.assertTrue(j.all((j.confidence == j.confidence_1) & (hl.abs(j.p_de_novo - j.p_de_novo_1) < 1e-4)))
def main(args):
################################
truthset_table = hl.read_table(args.truthset_table)
#################################
group = "raw"
fam = args.trio_fam
pedigree = hl.Pedigree.read(fam)
#mt = mt.annotate_rows(family_stats=famstats_ht[mt.row_key].family_stats)
#mt=mt.checkpoint(f'{args.output_dir}/Sanger_cohorts_family_stats.mt', overwrite=True)
mt=hl.read_matrix_table(f'{args.output_dir}/MegaWESSanger_cohorts_sampleQC_filtered.mt')
mt = hl.split_multi_hts(
mt, keep_star=False, left_aligned=False, permit_shuffle=True)
mt=mt.checkpoint(f'{args.output_dir}/MegaWESSanger_cohorts_sampleQC_filtered_split_multi.mt', overwrite=True)
priors = hl.read_table(args.priors)
mt = mt.annotate_rows(gnomad_maf=priors[mt.row_key].maf)
mt = mt.checkpoint(
f'{lustre_dir}/Sanger_cohorts_family_stats_gnomad_AF.mt', overwrite=True)
de_novo_table = hl.de_novo(
mt, pedigree, mt.gnomad_maf)
de_novo_table = de_novo_table.key_by(
'locus', 'alleles').collect_by_key('de_novo_data')
de_novo_table.write(
f'{args.output_dir}/Sanger_cohort_denovo_table.ht', overwrite=True)
def test_de_novo(self):
mt = hl.import_vcf(resource('denovo.vcf'))
mt = mt.filter_rows(mt.locus.in_y_par(), keep=False) # de_novo_finder doesn't know about y PAR
ped = hl.Pedigree.read(resource('denovo.fam'))
r = hl.de_novo(mt, ped, mt.info.ESP)
r = r.select(
prior=r.prior,
kid_id=r.proband.s,
dad_id=r.father.s,
mom_id=r.mother.s,
p_de_novo=r.p_de_novo,
confidence=r.confidence).key_by('locus', 'alleles', 'kid_id', 'dad_id', 'mom_id')
truth = hl.import_table(resource('denovo.out'), impute=True, comment='#')
truth = truth.select(
locus=hl.locus(truth['Chr'], truth['Pos']),
alleles=[truth['Ref'], truth['Alt']],
kid_id=truth['Child_ID'],
dad_id=truth['Dad_ID'],
mom_id=truth['Mom_ID'],
p_de_novo=truth['Prob_dn'],
confidence=truth['Validation_Likelihood'].split('_')[0]).key_by('locus', 'alleles', 'kid_id', 'dad_id',
'mom_id')
j = r.join(truth, how='outer')
self.assertTrue(j.all((j.confidence == j.confidence_1) & (hl.abs(j.p_de_novo - j.p_de_novo_1) < 1e-4)))
def compute_samocha_denovos(mt, pedigree):
gnomad_ht = hl.read_table("gs://gnomad-public/release/2.1.1/liftover_grch38/ht/exomes/gnomad.exomes.r2.1.1.sites.liftover_grch38.ht")
gnomad_ht = hl.split_multi_hts(gnomad_ht)
de_novo_priors_ht = gnomad_ht.select(AF=gnomad_ht.freq[gnomad_ht.freq_index_dict["gnomad"]].AF)
de_novos_ht = hl.de_novo(mt, pedigree, de_novo_priors_ht[mt.row_key].AF)
de_novos_ht = de_novos_ht.transmute(proband=de_novos_ht.proband.s, father=de_novos_ht.father.s, mother=de_novos_ht.mother.s)
de_novos_ht = de_novos_ht.annotate(proband_AB=de_novos_ht.proband_entry.AD[1]/(de_novos_ht.proband_entry.AD[0]+de_novos_ht.proband_entry.AD[1]))
de_novos_ht = de_novos_ht.annotate(proband_DP=de_novos_ht.proband_entry.DP)
de_novos_ht = de_novos_ht.annotate(proband_GQ=de_novos_ht.proband_entry.GQ)
de_novos_ht = de_novos_ht.annotate(proband_GT=de_novos_ht.proband_entry.GT)
de_novos_ht = de_novos_ht.annotate(father_AB=de_novos_ht.father_entry.AD[1]/(de_novos_ht.father_entry.AD[0]+de_novos_ht.father_entry.AD[1]))
de_novos_ht = de_novos_ht.annotate(father_DP=de_novos_ht.father_entry.DP)
de_novos_ht = de_novos_ht.annotate(father_GQ=de_novos_ht.father_entry.GQ)
de_novos_ht = de_novos_ht.annotate(father_GT=de_novos_ht.father_entry.GT)
de_novos_ht = de_novos_ht.annotate(mother_AB=de_novos_ht.mother_entry.AD[1]/(de_novos_ht.mother_entry.AD[0]+de_novos_ht.mother_entry.AD[1]))
de_novos_ht = de_novos_ht.annotate(mother_DP=de_novos_ht.mother_entry.DP)
de_novos_ht = de_novos_ht.annotate(mother_GQ=de_novos_ht.mother_entry.GQ)
de_novos_ht = de_novos_ht.annotate(mother_GT=de_novos_ht.mother_entry.GT)
de_novos_ht = de_novos_ht.drop(de_novos_ht.proband_entry, de_novos_ht.father_entry, de_novos_ht.mother_entry)
return de_novos_ht
def main(args):
################################
truthset_table = hl.read_table(args.truthset_table)
#################################
group = "raw"
mt = hl.read_matrix_table(args.matrixtable)
mt = hl.split_multi_hts(mt,
keep_star=False,
left_aligned=False,
permit_shuffle=True)
mt = mt.checkpoint(
f'{args.output_dir}/variant_qc/MegaWESSanger_cohorts_sampleQC_filtered_autosomes_split.mt',
overwrite=True)
fam = args.trio_fam
pedigree = hl.Pedigree.read(fam)
trio_dataset = hl.trio_matrix(mt, pedigree, complete_trios=True)
trio_dataset.write(f'{args.output_dir}/MegaWES_trio_table.mt',
overwrite=True)
(ht1, famstats_ht) = generate_family_stats(mt, fam)
print("Writing mt and family stats_ht")
ht1.write(f'{args.output_dir}/MegaWES_family_stats.ht', overwrite=True)
#famstats_ht.write(
# f'{args.output_dir}/MegaWES_family_stats.ht', overwrite=True)
mt = mt.annotate_rows(family_stats=ht1[mt.row_key].family_stats)
mt = mt.checkpoint(f'{args.output_dir}/MegaWES_family_stats.mt',
overwrite=True)
#(mt1, famstats_ht) = generate_family_stats(mt, fam)
#print("Writing mt and family stats_ht")
#mt1.write(f'{tmp_dir}/Sanger_cohorts_family_stats.mt', overwrite=True)
# famstats_ht.write(
# f'{tmp_dir}/Sanger_cohorts_family_stats.ht', overwrite=True)
#mt = mt.annotate_rows(family_stats=ht[mt.row_key].family_stats)
#mt.write(f'{tmp_dir}/Sanger_cohorts_family_stats.mt', overwrite=True)
priors = hl.read_table(args.priors)
mt = mt.annotate_rows(gnomad_maf=priors[mt.row_key].maf)
mt = mt.checkpoint(
f'{lustre_dir}/variant_qc/MegaWES_family_stats_gnomad_AF.mt',
overwrite=True)
#mt = hl.split_multi_hts(mt, keep_star=False, left_aligned=False, permit_shuffle=True)
de_novo_table = hl.de_novo(mt, pedigree, mt.gnomad_maf)
de_novo_table = de_novo_table.key_by(
'locus', 'alleles').collect_by_key('de_novo_data')
de_novo_table.write(
f'{args.output_dir}/variant_qc/MegaWES_denovo_table.ht',
overwrite=True)
def generate_de_novos(mt: hl.MatrixTable, fam_file: str, freq_data: hl.Table) -> hl.Table:
mt = mt.select_cols()
fam_ht = read_fam(fam_file).key_by()
fam_ht = fam_ht.select(
s=[fam_ht.s, fam_ht.pat_id, fam_ht.mat_id]).explode('s').key_by('s')
mt = mt.filter_cols(hl.is_defined(fam_ht[mt.s]))
mt = mt.select_rows()
mt = hl.split_multi_hts(mt)
mt = mt.annotate_rows(family_stats=freq_data[mt.row_key].family_stats)
ped = hl.Pedigree.read(fam_file, delimiter='\\t')
de_novo_table = hl.de_novo(
mt, ped, mt.family_stats[0].unrelated_qc_callstats.AF[1])
de_novo_table = de_novo_table.key_by(
'locus', 'alleles').collect_by_key('de_novo_data')
return de_novo_table
def main(args):
################################
truthset_table = hl.read_table(args.truthset_table)
#################################
group = "raw"
mt = hl.read_matrix_table(args.matrixtable)
fam = args.trio_fam
pedigree = hl.Pedigree.read(fam)
trio_dataset = hl.trio_matrix(mt, pedigree, complete_trios=True)
trio_dataset.write(f'{args.output_dir}/Sanger_cohort_trio_table.mt',
overwrite=True)
(mt1, famstats_ht) = generate_family_stats(mt, fam)
print("Writing mt and family stats_ht")
mt1.write(f'{args.output_dir}/Sanger_cohorts_family_stats.mt',
overwrite=True)
famstats_ht.write(f'{args.output_dir}/Sanger_cohorts_family_stats.ht',
overwrite=True)
mt = mt.annotate_rows(family_stats=famstats_ht[mt.row_key].family_stats)
mt.write(f'{args.output_dir}/Sanger_cohorts_family_stats.mt',
overwrite=True)
mt = hl.read_matrix_table(
f'{temp_dir}/ddd-elgh-ukbb/variant_qc/Sanger_cohorts_family_stats.mt')
priors = hl.read_table(args.priors)
mt = mt.annotate_rows(gnomad_maf=priors[mt.row_key].maf)
# mt = mt.checkpoint(
# f'{tmp_dir}/Sanger_cohorts_family_stats_gnomad_AF.mt', overwrite=True)
de_novo_table = hl.de_novo(mt, pedigree, mt.gnomad_maf)
de_novo_table = de_novo_table.key_by(
'locus', 'alleles').collect_by_key('de_novo_data')
de_novo_table.write(f'{args.output_dir}/Sanger_cohort_denovo_table.ht',
overwrite=True)
logger.info(f"Reading pedigree file {args.fam}")
pedigree = hl.Pedigree.read(args.fam)
logger.info(f"Importing vcf file {args.vcf}")
data = hl.import_vcf(args.vcf,
call_fields=['GT'],
skip_invalid_loci=True,
force_bgz=True)
data = hl.split_multi_hts(data)
data = data.annotate_rows(AC=data.info.AC[data.a_index - 1],
iAF=data.info.AF[data.a_index - 1])
data = hl.variant_qc(data)
logger.info("Applying de novo filter...")
de_novo_scores = hl.de_novo(data,
pedigree,
pop_frequency_prior=data.variant_qc.AF[-1])
de_novo_mt = de_novo_scores.to_matrix_table(row_key=['locus', 'alleles'],
col_key=['id'])
de_novo_data = data.annotate_entries(p_de_novo=de_novo_mt[(data.locus,
data.alleles),
data.s].p_de_novo)
logger.info("Annotating trio data...")
trio_mt = hl.trio_matrix(de_novo_data, pedigree, complete_trios=True)
de_novo_data = de_novo_data.annotate_entries(
mother=trio_mt[(de_novo_data.locus, de_novo_data.alleles),
de_novo_data.s].mother_entry,
father=trio_mt[(de_novo_data.locus, de_novo_data.alleles),
de_novo_data.s].father_entry,
)
def run_pipeline(args):
hl.init(log='./hail_annotation_pipeline.log')
'''
mt = hl.read_matrix_table('/gpfs/ycga/project/gruber/nsd35/hail_DeNovo/PCGC11.mt')
pprint.pprint(mt.count_cols()) # output: 1100
pprint.pprint(mt.count_rows()) # output: 1493771
mt = generate_split_alleles(mt)
pprint.pprint(mt.count_cols())
pprint.pprint(mt.count_rows())
table = (hl.import_table('/gpfs/ycga/project/gruber/nsd35/hail_DeNovo/IDs_keep.txt', impute=True).key_by('Sample'))
mt = mt.annotate_cols(should_retain = table[mt.s].should_retain)
mt = mt.filter_cols(mt.should_retain == 'yes', keep=True)
pprint.pprint(mt.count_cols())
pprint.pprint(mt.count_rows())
mt = mt.annotate_rows(gt_stats = hl.agg.call_stats(mt.GT, mt.alleles))
mt = mt.filter_rows(mt.row.gt_stats.AC[1] == 0, keep=False)
pprint.pprint(mt.count_cols())
pprint.pprint(mt.count_rows())
mt.write('pcgc11_subset.mt',overwrite=True)
'''
'''
mt = hl.read_matrix_table('pcgc11_subset.mt')
mt = hl.vep(mt, 'vep85-loftee-ruddle.json')
mt.write('pcgc11_subset_vep.mt',overwrite=True)
'''
#mt = hl.read_matrix_table('pcgc11_subset.mt')
#pprint.pprint(mt.count_cols())
#pprint.pprint(mt.count_rows())
#pprint.pprint(mt.describe())
#pprint.pprint(mt.show(include_row_fields=True))
#pprint.pprint(mt.row_key)
mt = hl.read_matrix_table('pcgc11_subset_vep.mt')
#pprint.pprint(mt_vep.count_cols())
#pprint.pprint(mt_vep.count_rows())
#pprint.pprint(mt_vep.describe())
mt = mt.annotate_rows(
sortedTranscriptConsequences=
get_expr_for_vep_sorted_transcript_consequences_array(vep_root=mt.vep))
pprint.pprint(mt.describe())
mt = mt.annotate_rows(
gene_symbol=hl.cond(mt.sortedTranscriptConsequences.size() > 0,
mt.sortedTranscriptConsequences[0].gene_symbol,
hl.null(hl.tstr)),
major_consequence=hl.cond(
mt.sortedTranscriptConsequences.size() > 0,
mt.sortedTranscriptConsequences[0].major_consequence,
hl.null(hl.tstr)),
hgvs=hl.cond(mt.sortedTranscriptConsequences.size() > 0,
mt.sortedTranscriptConsequences[0].hgvs,
hl.null(hl.tstr)),
category=hl.cond(mt.sortedTranscriptConsequences.size() > 0,
mt.sortedTranscriptConsequences[0].category,
hl.null(hl.tstr)),
canonical=hl.cond(mt.sortedTranscriptConsequences.size() > 0,
mt.sortedTranscriptConsequences[0].canonical, -1))
#pprint.pprint(mt.describe())
#pprint.pprint(mt.show(include_row_fields=True))
gnomad_exomes_ht = hl.read_table(
'/gpfs/ycga/project/lek/shared/data/gnomad/gnomad.exomes.r2.1.1.sites.ht'
)
#pprint.pprint(gnomad_exomes_ht.describe())
#pprint.pprint(gnomad_exomes_ht.show())
#global_meta = hl.eval(gnomad_exomes_ht.globals.freq_index_dict)
#pprint.pprint(global_meta)
#mt = mt.annotate_rows(gnomad_af = gnomad_exomes_ht[mt.row_key].freq[0].AF)
mt = mt.annotate_rows(
gnomad_af=hl.cond(hl.is_defined(gnomad_exomes_ht[mt.row_key]),
gnomad_exomes_ht[mt.row_key].freq[0].AF, 0.0))
#pprint.pprint(mt.describe())
#pprint.pprint(mt.show(include_row_fields=True))
#pprint.pprint(mt.count_cols())
#pprint.pprint(mt.count_rows())
#pprint.pprint(mt.major_consequence.show())
#mt = mt.filter_rows(mt.gnomad_af > 0.0004, keep=False)
#pprint.pprint(mt.count_cols())
#pprint.pprint(mt.count_rows()) #552,067 114,297
#pprint.pprint(mt.show(include_row_fields=True))
#pprint.pprint(mt.major_consequence.show())
pedigree = hl.Pedigree.read(
'/gpfs/ycga/project/gruber/nsd35/hail_DeNovo/PCGC11.fam')
de_novo_results = (hl.de_novo(mt,
pedigree,
pop_frequency_prior=mt.gnomad_af)).key_by(
'locus', 'alleles')
#pprint.pprint(de_novo_results.describe())
#de_novo_results = hl.de_novo(mt, pedigree, pop_frequency_prior=gnomad_exomes_ht[mt.row_key].freq[0].AF)
#de_novo_results = de_novo_results.filter(de_novo_results.confidence == "HIGH")
#pprint.pprint(de_novo_results.key)
#ht = mt.rows()
#pprint.pprint(ht.describe())
#pprint.pprint(ht.show())
'''
de_novo_results = de_novo_results.annotate(
gene=ht[de_novo_results.key].gene_symbol,
major_consequence=ht[de_novo_results.key].major_consequence,
hgvs=ht[de_novo_results.key].hgvs,
category=ht[de_novo_results.key].category,
canonical=ht[de_novo_results.key].canonical,
)
'''
#pprint.pprint(de_novo_results.show())
de_novo_results.export('denovo_results.tsv')
'''
def main(args):
group = "raw"
mt = hl.read_matrix_table(args.matrixtable)
# Truthset
mt = hl.variant_qc(mt)
truthset_ht = get_truth_ht(args.omni, args.mills, args.thousand_genomes,
args.hapmap)
truthset_ht.write(f'{args.output_dir}/variant_qc/truthset_table.ht',
overwrite=True)
# Trio data
# trio annotation:
logger.info("Trio annotation and writing trios_adj.mt")
mt_adj = annotate_adj(mt)
fam = args.trio_fam
pedigree = hl.Pedigree.read(fam)
trio_dataset = hl.trio_matrix(mt_adj, pedigree, complete_trios=True)
trio_dataset.checkpoint(
f'{args.output_dir}/variant_qc/MegaWES_trios_adj.mt', overwrite=True)
logger.info("Trio stats and writing MegaWes_stats.ht")
trio_stats_ht = generate_trio_stats(trio_dataset,
autosomes_only=True,
bi_allelic_only=True)
trio_stats_ht.write(f'{args.output_dir}/variant_qc/MegaWES_stats.ht',
overwrite=True)
# inbreeding ht
mt_inbreeding = mt.annotate_rows(
InbreedingCoeff=bi_allelic_site_inbreeding_expr(mt.GT))
mt = mt.key_rows_by('locus').distinct_by_row().key_rows_by(
'locus', 'alleles')
ht_inbreeding = mt_inbreeding.rows()
# allele data and qc_ac ht
allele_data_ht = generate_allele_data(mt)
qc_ac_ht = generate_ac(mt, fam)
logger.info("Writing tables for inbreeding, allele counts")
ht_inbreeding.write(
f'{args.output_dir}/variant_qc/MegaWES_inbreeding_new.ht',
overwrite=True)
qc_ac_ht.write(f'{args.output_dir}/variant_qc/MegaWES_qc_ac_new.ht',
overwrite=True)
allele_data_ht.write(
f'{args.output_dir}/variant_qc/MegaWES_allele_data_new.ht',
overwrite=True)
# Trio matrix table
logger.info("Split multi allelic variants and write mt")
mt = hl.split_multi_hts(mt,
keep_star=False,
left_aligned=False,
permit_shuffle=True)
mt = mt.checkpoint(
f'{args.output_dir}/variant_qc/MegaWESSanger_cohorts_sampleQC_filtered_split.mt',
overwrite=True)
fam = args.trio_fam
pedigree = hl.Pedigree.read(fam)
logger.info("Trio matrixtable generation:")
trio_dataset = hl.trio_matrix(mt, pedigree, complete_trios=True)
trio_dataset.write(f'{args.output_dir}/variant_qc/MegaWES_trio_table.mt',
overwrite=True)
# Family stats
logger.info("Family stats")
(ht1, famstats_ht) = generate_family_stats(mt, fam)
print("Writing mt and family stats_ht")
ht1.write(f'{args.output_dir}/variant_qc/MegaWES_family_stats.ht',
overwrite=True)
mt = mt.annotate_rows(family_stats=ht1[mt.row_key].family_stats)
mt = mt.checkpoint(f'{args.output_dir}/variant_qc/MegaWES_family_stats.mt',
overwrite=True)
#Family stats with Allele Frequencies from gnomad
logger.info("Family stats with gnomad AF")
priors = hl.read_table(args.priors)
mt = mt.annotate_rows(gnomad_maf=priors[mt.row_key].maf)
mt = mt.checkpoint(
f'{lustre_dir}/variant_qc/MegaWES_family_stats_gnomad_AF.mt',
overwrite=True)
logger.info("De novo table cration")
#De novo table
de_novo_table = hl.de_novo(mt, pedigree, mt.gnomad_maf)
de_novo_table = de_novo_table.key_by(
'locus', 'alleles').collect_by_key('de_novo_data')
de_novo_table.write(
f'{args.output_dir}/variant_qc/MegaWES_denovo_table.ht',
overwrite=True)