def _is_dnm(
proband_gt: hl.expr.CallExpression,
father_gt: hl.expr.CallExpression,
mother_gt: hl.expr.CallExpression,
locus: hl.expr.LocusExpression,
proband_is_female: Optional[hl.expr.BooleanExpression],
) -> hl.expr.BooleanExpression:
"""
Helper method to get whether a given genotype combination is a DNM at a given locus with a given proband sex.
"""
if proband_is_female is None:
logger.warning(
"Since no proband sex expression was given to generate_trio_stats_expr, only DNMs in autosomes will be counted."
)
return hl.or_missing(
locus.in_autosome(),
proband_gt.is_het() & father_gt.is_hom_ref()
& mother_gt.is_hom_ref(),
)
return hl.cond(
locus.in_autosome_or_par() |
(proband_is_female & locus.in_x_nonpar()),
proband_gt.is_het() & father_gt.is_hom_ref()
& mother_gt.is_hom_ref(),
hl.or_missing(~proband_is_female,
proband_gt.is_hom_var() & father_gt.is_hom_ref()),
)
def get_adj_expr(
gt_expr: hl.expr.CallExpression,
gq_expr: Union[hl.expr.Int32Expression, hl.expr.Int64Expression],
dp_expr: Union[hl.expr.Int32Expression, hl.expr.Int64Expression],
ad_expr: hl.expr.ArrayNumericExpression,
adj_gq: int = 20,
adj_dp: int = 10,
adj_ab: float = 0.2,
haploid_adj_dp: int = 10
) -> hl.expr.BooleanExpression:
"""
Gets adj genotype annotation.
Defaults correspond to gnomAD values.
"""
return (
(gq_expr >= adj_gq) &
hl.cond(
gt_expr.is_haploid(),
dp_expr >= haploid_adj_dp,
dp_expr >= adj_dp
) &
(
hl.case()
.when(~gt_expr.is_het(), True)
.when(gt_expr.is_het_ref(), ad_expr[gt_expr[1]] / dp_expr >= adj_ab)
.default((ad_expr[gt_expr[0]] / dp_expr >= adj_ab ) & (ad_expr[gt_expr[1]] / dp_expr >= adj_ab ))
)
)
def adjusted_sex_ploidy_expr(
locus_expr: hl.expr.LocusExpression,
gt_expr: hl.expr.CallExpression,
karyotype_expr: hl.expr.StringExpression,
xy_karyotype_str: str = "XY",
xx_karyotype_str: str = "XX",
) -> hl.expr.CallExpression:
"""
Creates an entry expression to convert males to haploid on non-PAR X/Y and females to missing on Y
:param locus_expr: Locus
:param gt_expr: Genotype
:param karyotype_expr: Karyotype
:param xy_karyotype_str: Male sex karyotype representation
:param xx_karyotype_str: Female sex karyotype representation
:return: Genotype adjusted for sex ploidy
"""
male = karyotype_expr == xy_karyotype_str
female = karyotype_expr == xx_karyotype_str
x_nonpar = locus_expr.in_x_nonpar()
y_par = locus_expr.in_y_par()
y_nonpar = locus_expr.in_y_nonpar()
return (hl.case(missing_false=True).when(
female & (y_par | y_nonpar), hl.null(hl.tcall)).when(
male & (x_nonpar | y_nonpar) & gt_expr.is_het(),
hl.null(hl.tcall)).when(male & (x_nonpar | y_nonpar),
hl.call(gt_expr[0],
phased=False)).default(gt_expr))
def age_hists_expr(
adj_expr: hl.expr.BooleanExpression,
gt_expr: hl.expr.CallExpression,
age_expr: hl.expr.NumericExpression,
lowest_boundary: int = 30,
highest_boundary: int = 80,
n_bins: int = 10,
) -> hl.expr.StructExpression:
"""
Returns a StructExpression with the age histograms for hets and homs.
:param adj_expr: Entry expression containing whether a genotype is high quality (adj) or not
:param gt_expr: Entry expression containing the genotype
:param age_expr: Col expression containing the sample's age
:param lowest_boundary: Lowest bin boundary (any younger sample will be binned in n_smaller)
:param highest_boundary: Highest bin boundary (any older sample will be binned in n_larger)
:param n_bins: Total number of bins
:return: A struct with `age_hist_het` and `age_hist_hom`
"""
return hl.struct(
age_hist_het=hl.agg.filter(
adj_expr & gt_expr.is_het(),
hl.agg.hist(age_expr, lowest_boundary, highest_boundary, n_bins),
),
age_hist_hom=hl.agg.filter(
adj_expr & gt_expr.is_hom_var(),
hl.agg.hist(age_expr, lowest_boundary, highest_boundary, n_bins),
),
)
def call_to_one_hot_alleles_array(call: hl.expr.CallExpression, alleles: hl.expr.ArrayExpression) -> hl.expr.ArrayExpression:
"""
Get the set of all different one-hot-encoded allele-vectors in a genotype call.
It is returned as an ordered array where the first vector corresponds to the first allele,
and the second vector (only present if het) the second allele.
:param CallExpression call: genotype
:param ArrayExpression alleles: Alleles at the site
:return: Array of one-hot-encoded alleles
:rtype: ArrayExpression
"""
return hl.cond(
call.is_het(),
hl.array([
hl.call(call[0]).one_hot_alleles(alleles),
hl.call(call[1]).one_hot_alleles(alleles),
]),
hl.array([hl.call(call[0]).one_hot_alleles(alleles)])
)
def call_to_one_hot_alleles_array(call: hl.expr.CallExpression, alleles: hl.expr.ArrayExpression) -> hl.expr.ArrayExpression:
"""
Get the set of all different one-hot-encoded allele-vectors in a genotype call.
It is returned as an ordered array where the first vector corresponds to the first allele,
and the second vector (only present if het) the second allele.
:param CallExpression call: genotype
:param ArrayExpression alleles: Alleles at the site
:return: Array of one-hot-encoded alleles
:rtype: ArrayExpression
"""
return hl.cond(
call.is_het(),
hl.array([
hl.call(call[0]).one_hot_alleles(alleles),
hl.call(call[1]).one_hot_alleles(alleles),
]),
hl.array([hl.call(call[0]).one_hot_alleles(alleles)])
)
