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Merged
merged 18 commits into from
Nov 12, 2024
Merged

handle wes/wgs inheritance edge case #4440

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babadd7
almost working
jklugherz Oct 18, 2024
7115f81
updates
jklugherz Oct 18, 2024
fb1dc19
or_missing
jklugherz Oct 23, 2024
de664cd
fix sample tracking logic
jklugherz Oct 23, 2024
8d9d25d
f string
jklugherz Oct 23, 2024
877abbc
another pass
jklugherz Oct 28, 2024
fb88af9
minor things
jklugherz Oct 28, 2024
773ba0c
less code
jklugherz Oct 29, 2024
18d1d63
reuse as much code from _annotate_families_inheritance
jklugherz Oct 31, 2024
4d58e03
rstructure passes inheritance field
jklugherz Nov 4, 2024
e1edb07
fix _family_has_valid_inheritance
jklugherz Nov 4, 2024
d806332
fix up test cases
jklugherz Nov 4, 2024
3206941
oop
jklugherz Nov 4, 2024
ef5a4ec
typo
jklugherz Nov 4, 2024
2d5d07f
typo 2
jklugherz Nov 4, 2024
f82c0fe
PR comments
jklugherz Nov 5, 2024
0158391
comments
jklugherz Nov 7, 2024
0b542e1
extra lines
jklugherz Nov 7, 2024
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7 changes: 7 additions & 0 deletions hail_search/definitions.py
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Original file line number Diff line number Diff line change
Expand Up @@ -12,6 +12,13 @@ def family_entries_field(self) -> str:
SampleType.WGS: 'wgs_family_entries',
}[self]

@property
def failed_family_sample_field(self) -> str:
return {
SampleType.WES: f'wes_failed_family_sample_indices',
SampleType.WGS: f'wgs_failed_family_sample_indices',
}[self]

@property
def passes_inheritance_field(self) -> str:
return {
Expand Down
11 changes: 6 additions & 5 deletions hail_search/queries/base.py
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Original file line number Diff line number Diff line change
Expand Up @@ -472,7 +472,7 @@ def _apply_entry_filters(ht):
def _filter_single_entries_table(self, ht, project_families, inheritance_filter=None, quality_filter=None, is_merged_ht=False, **kwargs):
ht, sorted_family_sample_data = self._add_entry_sample_families(ht, project_families, is_merged_ht)
ht = self._filter_quality(ht, quality_filter, **kwargs)
ht, ch_ht = self._filter_inheritance(
ht, ch_ht, _, _ = self._filter_inheritance(
ht, None, inheritance_filter, sorted_family_sample_data,
)
ht = self._apply_entry_filters(ht)
Expand Down Expand Up @@ -588,8 +588,9 @@ def _filter_inheritance(
lambda entries: hl.or_missing(entries.any(any_valid_entry), entries)
)})

ch_ht_entry_indices_by_gt = None
if self._has_comp_het_search:
comp_het_ht = self._annotate_families_inheritance(
comp_het_ht, ch_ht_entry_indices_by_gt = self._annotate_families_inheritance(
comp_het_ht if comp_het_ht is not None else ht, COMPOUND_HET, inheritance_filter,
sorted_family_sample_data, annotation, entries_ht_field
)
Expand All @@ -598,12 +599,12 @@ def _filter_inheritance(
# No sample-specific inheritance filtering needed
sorted_family_sample_data = []

ht = None if self._inheritance_mode == COMPOUND_HET else self._annotate_families_inheritance(
ht, ht_entry_indices_by_gt = (None, None) if self._inheritance_mode == COMPOUND_HET else self._annotate_families_inheritance(
ht, self._inheritance_mode, inheritance_filter, sorted_family_sample_data,
annotation, entries_ht_field
)

return ht, comp_het_ht
return ht, comp_het_ht, ht_entry_indices_by_gt, ch_ht_entry_indices_by_gt

def _annotate_families_inheritance(
self, ht, inheritance_mode, inheritance_filter, sorted_family_sample_data,
Expand Down Expand Up @@ -644,7 +645,7 @@ def _annotate_families_inheritance(
)
})

return ht
return ht, entry_indices_by_gt

def _get_family_passes_quality_filter(self, quality_filter, ht, **kwargs):
quality_filter = quality_filter or {}
Expand Down
118 changes: 97 additions & 21 deletions hail_search/queries/mito.py
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Original file line number Diff line number Diff line change
Expand Up @@ -206,37 +206,70 @@ def _filter_entries_ht_both_sample_types(

ch_ht = None
family_guid_idx_map = defaultdict(dict)
family_sample_idx_map = defaultdict(lambda: defaultdict(dict))
for sample_type, sorted_family_sample_data in sample_types:
ht, ch_ht = self._filter_inheritance(
ht, ch_ht, ht_idx_by_gt_map, ch_idx_by_gt_map = self._filter_inheritance(
ht, ch_ht, inheritance_filter, sorted_family_sample_data,
annotation=sample_type.passes_inheritance_field, entries_ht_field=sample_type.family_entries_field
)
ht = self._annotate_failed_family_samples_inheritance(
ht, ht_idx_by_gt_map,
annotation=sample_type.failed_family_sample_field, entries_ht_field=sample_type.family_entries_field
)
ch_ht = self._annotate_failed_family_samples_inheritance(
ch_ht, ch_idx_by_gt_map,
annotation=sample_type.failed_family_sample_field, entries_ht_field=sample_type.family_entries_field
)

for family_idx, samples in enumerate(sorted_family_sample_data):
family_guid = samples[0]['familyGuid']
family_guid_idx_map[family_guid][sample_type.value] = family_idx
for sample_idx, sample in enumerate(samples):
family_sample_idx_map[family_guid][sample['sampleId']][sample_type.value] = sample_idx

family_idx_map = hl.dict(family_guid_idx_map)
ht = self._apply_multi_sample_type_entry_filters(ht, family_idx_map)
ch_ht = self._apply_multi_sample_type_entry_filters(ch_ht, family_idx_map)
family_guid_idx_map = hl.dict(family_guid_idx_map)
family_sample_idx_map = hl.dict(family_sample_idx_map)
ht = self._apply_multi_sample_type_entry_filters(ht, family_guid_idx_map, family_sample_idx_map)
ch_ht = self._apply_multi_sample_type_entry_filters(ch_ht, family_guid_idx_map, family_sample_idx_map)
return ht, ch_ht

def _apply_multi_sample_type_entry_filters(self, ht, family_idx_map):
def _annotate_failed_family_samples_inheritance(
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This feels incredibly similar to _annotate_families_inheritance. Rather than making a whole separate function for this, you could make a much more tightly scoped conditional helper to pass into _annotate_families_inheritance, perhaps just for the lambda function applied to the hl.enumerate(ht[entries_ht_field]).starmap(

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I implemented this, but because I don't want the single sample type families that come originally through the mito class code path to call the mito 'family_passes_inheritance_filter' function, I'm still passing a family_passes_inheritance_filter function to _filter_inheritance instead of using python inheritance here. Do you know if there's a cleaner way to do this?

self, ht, entry_indices_by_gt, annotation, entries_ht_field,
):
if ht is None:
return ht

ht = ht.annotate(**{annotation: hl.empty_dict(hl.tint32, hl.tarray(hl.tint32))})
# print(annotation, ht[annotation].collect())

for genotype, entry_indices in entry_indices_by_gt.items():
if not entry_indices:
continue
# print(genotype, entry_indices)
entry_indices = hl.dict(entry_indices)
ht = ht.annotate(
**{annotation: hl.dict(
hl.enumerate(ht[entries_ht_field]).starmap(
lambda family_index, entries: hl.bind(
lambda failed_samples: hl.tuple((
family_index,
ht[annotation].get(family_index, hl.empty_array(hl.tint32)).extend(failed_samples)
)),
entry_indices.get(family_index).filter(lambda sample_i: ~self.GENOTYPE_QUERY_MAP[genotype](entries[sample_i].GT))
)
)
)})
# print(annotation, ht[annotation].collect())
return ht

def _apply_multi_sample_type_entry_filters(self, ht, family_idx_map, sample_idx_map):
if ht is None:
return ht

# Keep family from both sample types if either passes quality AND inheritance
for sample_type in SampleType:
ht = ht.annotate(**{
sample_type.family_entries_field: hl.enumerate(ht[sample_type.family_entries_field]).starmap(
lambda i, family_samples: hl.or_missing(
hl.bind(
lambda other_sample_type_idx: (
self._family_has_valid_sample_type_entries(ht, sample_type, i) |
self._family_has_valid_sample_type_entries(ht, sample_type.other_sample_type, other_sample_type_idx)
),
family_idx_map.get(hl.coalesce(family_samples)[0]['familyGuid']).get(sample_type.other_sample_type.value),
), family_samples)
)})
ht = self._apply_quality_entry_filters(ht, sample_type, family_idx_map)
ht = self._apply_inheritance_entry_filters(ht, sample_type, family_idx_map, sample_idx_map)

# Merge family entries and filters from both sample types
ht = ht.transmute(
Expand All @@ -252,14 +285,57 @@ def _apply_multi_sample_type_entry_filters(self, ht, family_idx_map):
# Filter out families with no valid entries in either sample type
return ht.filter(ht.family_entries.any(hl.is_defined))

def _apply_quality_entry_filters(self, ht, sample_type, family_idx_map):
return ht.annotate(**{
sample_type.family_entries_field: hl.enumerate(ht[sample_type.family_entries_field]).starmap(
lambda i, family_samples: hl.or_missing(
hl.bind(lambda other_sample_type_idx: (
self._family_has_valid_quality(ht, sample_type, i) |
self._family_has_valid_quality(ht, sample_type.other_sample_type, other_sample_type_idx)
), family_idx_map.get(hl.coalesce(family_samples)[0]['familyGuid']).get(sample_type.other_sample_type.value),
), family_samples)
)})

@staticmethod
def _family_has_valid_sample_type_entries(ht, sample_type, sample_type_family_idx):
# Note: This logic does not sufficiently handle case 2 here https://docs.google.com/presentation/d/1hqDV8ulhviUcR5C4PtNUqkCLXKDsc6pccgFVlFmWUAU/edit?usp=sharing
# and will need to be changed to support it - https://github.com/broadinstitute/seqr/issues/4403
def _family_has_valid_quality(ht, sample_type, sample_type_family_idx):
return (
hl.is_defined(sample_type_family_idx) &
hl.is_defined(ht[sample_type.passes_quality_field][sample_type_family_idx]) &
hl.is_defined(ht[sample_type.passes_inheritance_field][sample_type_family_idx])
hl.is_defined(ht[sample_type.passes_quality_field][sample_type_family_idx])
)

def _apply_inheritance_entry_filters(self, ht, sample_type, family_idx_map, sample_idx_map):
return ht.annotate(**{
sample_type.family_entries_field: hl.if_else(
hl.is_missing(ht[sample_type.family_entries_field]), # If family entries has already been filtered due to quality do nothing
ht[sample_type.family_entries_field],
hl.enumerate(ht[sample_type.family_entries_field]).starmap( # Else,
lambda family_i, family_samples: hl.or_missing(
hl.all(hl.enumerate(family_samples).starmap(
lambda sample_i, sample: hl.any( # For each sample in a family,
hl.bind(lambda other_sample_type_indices: ( # Get the sample and family index of the sample in the other sample type family_entries
hl.if_else(
hl.is_defined(sample_i) & hl.is_defined(other_sample_type_indices[1]), # If samples are present for both sample types,
( # Keep the family entries if family passes inheritance in either sample type.
hl.is_defined(ht[sample_type.passes_inheritance_field][family_i]) |
hl.is_defined(ht[sample_type.other_sample_type.passes_inheritance_field][other_sample_type_indices[0]])
), # Else, if sample is in only one sample type, check if that sample did not fail inheritance
self._family_sample_has_valid_inheritance(ht, sample_type, family_i, sample_i) |
self._family_sample_has_valid_inheritance(ht, sample_type.other_sample_type, other_sample_type_indices[0], other_sample_type_indices[1])
)
),(
family_idx_map.get(hl.coalesce(sample)['familyGuid']).get(sample_type.other_sample_type.value),
sample_idx_map.get(hl.coalesce(sample)['familyGuid']).get(hl.coalesce(sample)['sampleId']).get(sample_type.other_sample_type.value)),
))
)), family_samples)
))
})

@staticmethod
def _family_sample_has_valid_inheritance(ht, sample_type, family_idx, sample_idx):
return (
hl.is_defined(family_idx) &
hl.is_defined(sample_idx) &
~hl.is_defined(ht[sample_type.failed_family_sample_field][family_idx].contains(sample_idx))
)

def _get_sample_genotype(self, samples, r=None, include_genotype_overrides=False, select_fields=None, **kwargs):
Expand Down
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