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merged 3 commits into from
Nov 5, 2024
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handle sex aneuploidy in pipeline #945

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607401f
handle sex aneuploidy in pipeline
jklugherz Oct 30, 2024
9ef4364
extra file
jklugherz Oct 30, 2024
a62a595
old table
jklugherz Oct 30, 2024
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3 changes: 3 additions & 0 deletions v03_pipeline/lib/misc/family_loading_failures_test.py
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Original file line number Diff line number Diff line change
Expand Up @@ -62,6 +62,7 @@ def test_build_sex_check_lookup(self):
{'s': 'ROS_007_19Y05919_D1', 'predicted_sex': 'F'},
{'s': 'ROS_007_19Y05939_D1', 'predicted_sex': 'M'},
{'s': 'ROS_007_19Y05987_D1', 'predicted_sex': 'U'},
{'s': 'ROS_007_19Y05989_D1', 'predicted_sex': 'X0'},
],
hl.tstruct(
s=hl.tstr,
Expand All @@ -78,6 +79,7 @@ def test_build_sex_check_lookup(self):
'ROS_007_19Y05919_D1': Sex.FEMALE,
'ROS_007_19Y05939_D1': Sex.MALE,
'ROS_007_19Y05987_D1': Sex.UNKNOWN,
'ROS_007_19Y05989_D1': Sex.X0,
},
)

Expand Down Expand Up @@ -184,6 +186,7 @@ def test_get_families_failed_sex_check(self):
{'s': 'ROS_007_19Y05919_D1', 'predicted_sex': 'F'},
{'s': 'ROS_007_19Y05939_D1', 'predicted_sex': 'M'},
{'s': 'ROS_007_19Y05987_D1', 'predicted_sex': 'U'}, # Pedigree Sex F
{'s': 'ROS_007_19Y05989_D1', 'predicted_sex': 'XXX'},
],
hl.tstruct(
s=hl.tstr,
Expand Down
1 change: 1 addition & 0 deletions v03_pipeline/lib/misc/io_test.py
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Original file line number Diff line number Diff line change
Expand Up @@ -46,6 +46,7 @@ def test_import_imputed_sex(self) -> None:
hl.Struct(s='abc_1', predicted_sex='M'),
hl.Struct(s='abc_2', predicted_sex='F'),
hl.Struct(s='abc_3', predicted_sex='U'),
hl.Struct(s='abc_4', predicted_sex='XYY'),
],
)

Expand Down
12 changes: 10 additions & 2 deletions v03_pipeline/lib/misc/validation.py
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Original file line number Diff line number Diff line change
Expand Up @@ -173,9 +173,17 @@ def validate_imputed_sex_ploidy(
& (sex_check_ht[mt.s].predicted_sex == Sex.MALE.value)
)
| (
# At least one call is haploid but the sex is Female
# At least one call is haploid but the sex is Female, X0, XXY, XYY, or XXX
hl.agg.any(~mt.GT.is_diploid())
& (sex_check_ht[mt.s].predicted_sex == Sex.FEMALE.value)
& hl.literal(
{
Sex.FEMALE.value,
Sex.X0.value,
Sex.XYY.value,
Sex.XXY.value,
Sex.XXX.value,
},
).contains(sex_check_ht[mt.s].predicted_sex)
)
),
)
Expand Down
88 changes: 81 additions & 7 deletions v03_pipeline/lib/misc/validation_test.py
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Original file line number Diff line number Diff line change
Expand Up @@ -113,8 +113,18 @@ def test_validate_allele_type(self) -> None:

@patch('v03_pipeline.lib.misc.validation.Env')
def test_validate_imputed_sex_ploidy(self, mock_env: Mock) -> None:
female_sample = 'HG00731_1'
male_sample_1 = 'HG00732_1'
male_sample_2 = 'HG00732_1'
x0_sample = 'NA20899_1'
xxy_sample = 'NA20889_1'
xyy_sample = 'NA20891_1'
xxx_sample = 'NA20892_1'

mock_env.CHECK_SEX_AND_RELATEDNESS = True
sex_check_ht = hl.read_table(TEST_SEX_CHECK_1)

# All calls on X chromosome are valid
mt = hl.MatrixTable.from_parts(
rows={
'locus': [
Expand All @@ -125,42 +135,106 @@ def test_validate_imputed_sex_ploidy(self, mock_env: Mock) -> None:
),
],
},
cols={'s': ['HG00731_1', 'HG00732_1']},
cols={
's': [
female_sample,
male_sample_1,
x0_sample,
xxy_sample,
xyy_sample,
xxx_sample,
],
},
entries={
'GT': [
[
hl.Call(alleles=[0, 0], phased=False),
hl.Call(alleles=[0], phased=False),
hl.Call(alleles=[0, 0], phased=False), # X0
hl.Call(alleles=[0, 0], phased=False), # XXY
hl.Call(alleles=[0, 0], phased=False), # XYY
hl.Call(alleles=[0, 0], phased=False), # XXX
],
],
},
).key_rows_by('locus')
validate_imputed_sex_ploidy(mt, sex_check_ht)

# All calls on Y chromosome are valid
mt = hl.MatrixTable.from_parts(
rows={
'locus': [
hl.Locus(
contig='chrX',
contig='chrY',
position=1,
reference_genome='GRCh38',
),
],
},
# Male, Female, Male
cols={'s': ['HG00731_1', 'HG00732_1', 'NA19678_1']},
cols={
's': [
female_sample,
male_sample_1,
x0_sample,
xxy_sample,
xyy_sample,
xxx_sample,
],
},
entries={
'GT': [
[
hl.Call(alleles=[0], phased=False),
hl.Call(alleles=[0], phased=False),
hl.missing(hl.tcall),
hl.Call(alleles=[0], phased=False),
hl.missing(hl.tcall), # X0
hl.Call(alleles=[0, 0], phased=False), # XXY
hl.Call(alleles=[0, 0], phased=False), # XYY
hl.missing(hl.tcall), # XXX
],
],
},
).key_rows_by('locus')
validate_imputed_sex_ploidy(mt, sex_check_ht)

# Invalid X chromosome case
mt = hl.MatrixTable.from_parts(
rows={
'locus': [
hl.Locus(
contig='chrX',
position=1,
reference_genome='GRCh38',
),
],
},
cols={
's': [
female_sample,
male_sample_1,
male_sample_2,
x0_sample,
xxy_sample,
xyy_sample,
xxx_sample,
],
},
entries={
'GT': [
[
hl.Call(alleles=[0], phased=False), # invalid Female call
hl.Call(alleles=[0], phased=False), # valid Male call
hl.missing(hl.tcall), # invalid Male call
hl.Call(alleles=[0], phased=False), # invalid X0 call
hl.Call(alleles=[0], phased=False), # invalid XXY call
hl.missing(hl.tcall), # valid XYY call
hl.Call(alleles=[0, 0], phased=False), # valid XXX call
],
],
},
).key_rows_by('locus')
self.assertRaisesRegex(
SeqrValidationError,
'66.67% of samples have misaligned ploidy',
'57.14% of samples have misaligned ploidy',
validate_imputed_sex_ploidy,
mt,
sex_check_ht,
Expand Down
6 changes: 5 additions & 1 deletion v03_pipeline/lib/model/definitions.py
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Original file line number Diff line number Diff line change
Expand Up @@ -12,14 +12,18 @@ class Sex(str, Enum):
FEMALE = 'F'
MALE = 'M'
UNKNOWN = 'U'
XXX = 'XXX'
X0 = 'X0'
XXY = 'XXY'
XYY = 'XYY'

@property
def imputed_sex_value(self):
return {
Sex.MALE: 'Male',
Sex.FEMALE: 'Female',
Sex.UNKNOWN: 'Unknown',
}[self]
}.get(self, self.name)


class PipelineVersion(str, Enum):
Expand Down
3 changes: 2 additions & 1 deletion v03_pipeline/var/test/pedigrees/test_pedigree_6.tsv
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Expand Up @@ -4,4 +4,5 @@ R0116_sex_check_project2 family_1 family_1 ROS_006_18Y03227_D1 U
R0116_sex_check_project2 family_1 family_1 ROS_006_18Y03228_D1 ROS_006_18Y03226_D1 ROS_006_18Y03227_D1 F
R0116_sex_check_project2 family_2 family_2 ROS_007_19Y05919_D1 F
R0116_sex_check_project2 family_2 family_2 ROS_007_19Y05939_D1 F
R0116_sex_check_project2 family_2 family_2 ROS_007_19Y05987_D1 ROS_007_19Y05919_D1 ROS_007_19Y05939_D1 F
R0116_sex_check_project2 family_2 family_2 ROS_007_19Y05987_D1 ROS_007_19Y05919_D1 ROS_007_19Y05939_D1 F
R0116_sex_check_project2 family_2 family_2 ROS_007_19Y05989_D1 ROS_007_19Y05919_D1 ROS_007_19Y05939_D1 XXX
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@jklugherz jklugherz Oct 30, 2024

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need to confirm that pedigree file will also be delivered with sex aneupolodies matching those in the imputed sex file predicted_sex

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@hanars hanars Oct 30, 2024

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confirmed! This is how seqr would generate a pedigree file with an aneuploidy

1 change: 1 addition & 0 deletions v03_pipeline/var/test/sex_check/test_imputed_sex.tsv
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Original file line number Diff line number Diff line change
Expand Up @@ -2,3 +2,4 @@ entity:sample_id collaborator_participant_id collaborator_sample_id contaminatio
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SM-DPB5G abc_3 abc_3 0E+00 gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/432f8354-77e0-4381-9bb5-dfdc0633b5b2/PIE_OGI1433_002628_1.qc-coverage-region-1_coverage_metrics.csv gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/3dc623fa-2a45-4b3d-a0f8-fcdec09f9418/PIE_OGI1433_002628_1.cram.crai gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/895966ef-c705-4c18-952d-03863243a184/PIE_OGI1433_002628_1.cram.md5sum gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/96ca6d5f-fb23-4102-bb5e-c7bbfd194e1c/PIE_OGI1433_002628_1.cram ffb50687-165e-425a-a545-c3797d3a28d4 07.021.604.3.7.8 55729ba9-3ce4-47b3-9c3b-1148737ae40f 2024-04-17T15:07:57 99.670000000 gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/30f8e208-5d2d-4ce8-b835-695b5ed673f4/PIE_OGI1433_002628_1.mapping_metrics.csv DNA:DNA Genomic 41.910000000 Whole Blood:Whole Blood PT-25BR5 Pass PDO-32756 92.920000000 97.990000000 Unknown P-WG-0139 2017-05-19 04:00:00 Unknown RP-3062 gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/1641d1b2-1035-4cc3-9c8b-0c8cb430f56b/PIE_OGI1433_002628_1.vcf.gz.tbi gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/f5ba2708-899e-42e8-b287-fdf72c2e404d/PIE_OGI1433_002628_1.vcf.gz.md5sum gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/e925ee5d-a75e-471f-adfd-2756c8690069/PIE_OGI1433_002628_1.vcf.gz 156149580126.000000000 gs://datarepo-c41dc160-bucket/907593be-8862-4945-9e70-f758b6448b8d/df076bc5-9db8-44f0-a3fe-f693370634cc/PIE_OGI1433_002628_1.vc_metrics.csv
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4 changes: 2 additions & 2 deletions v03_pipeline/var/test/sex_check/test_sex_check_1.ht/README.txt
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This folder comprises a Hail (www.hail.is) native Table or MatrixTable.
Written with version 0.2.128-eead8100a1c1
Created at 2024/05/02 16:11:09
Written with version 0.2.132-678e1f52b999
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@jklugherz jklugherz Oct 30, 2024

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added 4 new samples with the 4 new sexes

Created at 2024/10/29 17:04:32
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