def test_gene_predictions_two_genes():
## GIVEN a empty list of genes
gene = {
"hgnc_symbol": "AAA",
"sift_prediction": "deleterious",
"polyphen_prediction": "probably_damaging",
"region_annotation": "exonic",
"functional_annotation": "missense_variant",
"spliceai_score": 0.17,
"spliceai_position": -4,
"spliceai_prediction": ["ds 0.17 dp -4"],
}
gene2 = {
"hgnc_symbol": "BBB",
"sift_prediction": "tolerated",
"polyphen_prediction": "unknown",
"region_annotation": "exonic",
"functional_annotation": "synonymous_variant",
"spliceai_score": 0.9,
"spliceai_position": 5,
"spliceai_prediction": ["ds 0.9 dp 5"],
}
genes = [gene, gene2]
## WHEN parsing the gene predictions
res = predictions(genes)
## THEN assert the result is not filled
assert set(res["sift_predictions"]) == set(["AAA:deleterious", "BBB:tolerated"])
def test_gene_predictions_one_gene():
## GIVEN a list with one gene
gene = {
"sift_prediction": "deleterious",
"polyphen_prediction": "probably_damaging",
"region_annotation": "exonic",
"functional_annotation": "missense_variant",
"spliceai_score": 0.17,
"spliceai_position": -4,
"spliceai_prediction": ["ds 0.17 dp -4"],
}
genes = [gene]
## WHEN parsing the gene predictions
res = predictions(genes)
## THEN assert the result is filled
assert res == {
"sift_predictions": ["deleterious"],
"polyphen_predictions": ["probably_damaging"],
"region_annotations": ["exonic"],
"functional_annotations": ["missense_variant"],
"spliceai_scores": [0.17],
"spliceai_positions": [-4],
"spliceai_predictions": [["ds 0.17 dp -4"]],
}
def gene_variants(store,
pymongo_cursor,
variant_count,
institute_id,
page=1,
per_page=50):
"""Pre-process list of variants."""
skip_count = per_page * max(page - 1, 0)
more_variants = True if variant_count > (skip_count + per_page) else False
variant_res = pymongo_cursor.skip(skip_count).limit(per_page)
my_institutes = set(inst["_id"]
for inst in user_institutes(store, current_user))
variants = []
for variant_obj in variant_res:
# Populate variant case_display_name
variant_case_obj = store.case(case_id=variant_obj["case_id"])
if not variant_case_obj:
# A variant with missing case was encountered
continue
case_display_name = variant_case_obj.get("display_name")
variant_obj["case_display_name"] = case_display_name
# hide other institutes for now
other_institutes = set([variant_case_obj.get("owner")])
other_institutes.update(set(variant_case_obj.get("collaborators", [])))
if my_institutes.isdisjoint(other_institutes):
# If the user does not have access to the information we skip it
continue
genome_build = get_genome_build(variant_case_obj)
variant_genes = variant_obj.get("genes")
gene_object = update_HGNC_symbols(store, variant_genes, genome_build)
# Populate variant HGVS and predictions
variant_genes = variant_obj.get("genes")
hgvs_c = []
hgvs_p = []
if variant_genes is not None:
for gene_obj in variant_genes:
hgnc_id = gene_obj["hgnc_id"]
gene_symbol = gene(store, hgnc_id)["symbol"]
gene_symbols = [gene_symbol]
# gather HGVS info from gene transcripts
(hgvs_nucleotide, hgvs_protein) = get_hgvs(gene_obj)
hgvs_c.append(hgvs_nucleotide)
hgvs_p.append(hgvs_protein)
if len(gene_symbols) == 1:
variant_obj["hgvs"] = hgvs_str(gene_symbols, hgvs_p, hgvs_c)
# populate variant predictions for display
variant_obj.update(predictions(variant_genes))
variants.append(variant_obj)
return {"variants": variants, "more_variants": more_variants}
def test_gene_predictions_no_info():
## GIVEN a empty list of genes
genes = []
## WHEN parsing the gene predictions
res = predictions(genes)
## THEN assert the result is not filled
assert res == {
"sift_predictions": [],
"polyphen_predictions": [],
"region_annotations": [],
"functional_annotations": [],
}
def test_gene_predictions_one_gene_no_sift():
## GIVEN a empty list of genes
gene = {
"hgnc_symbol": "AAA",
"polyphen_prediction": "probably_damaging",
"region_annotation": "exonic",
"functional_annotation": "missense_variant",
}
genes = [gene]
## WHEN parsing the gene predictions
res = predictions(genes)
## THEN assert the result is not filled
assert res == {
"sift_predictions": ["-"],
"polyphen_predictions": ["probably_damaging"],
"region_annotations": ["exonic"],
"functional_annotations": ["missense_variant"],
}
def gene_variants(store, pymongo_cursor, variant_count, page=1, per_page=50):
"""Pre-process list of variants."""
skip_count = per_page * max(page - 1, 0)
more_variants = True if variant_count > (skip_count + per_page) else False
variant_res = pymongo_cursor.skip(skip_count).limit(per_page)
variants = []
for variant_obj in variant_res:
# Populate variant case_display_name
variant_case_obj = store.case(case_id=variant_obj["case_id"])
case_display_name = variant_case_obj.get("display_name")
variant_obj["case_display_name"] = case_display_name
genome_build = get_genome_build(variant_case_obj)
variant_genes = variant_obj.get("genes")
update_HGNC_symbols(store, variant_genes, genome_build)
# Populate variant HGVS and predictions
variant_genes = variant_obj.get("genes")
hgvs_c = []
hgvs_p = []
if variant_genes is not None:
for gene_obj in variant_genes:
hgnc_id = gene_obj["hgnc_id"]
gene_caption = store.hgnc_gene_caption(hgnc_id)
gene_symbols = [gene_caption["hgnc_symbol"]]
# gather HGVS info from gene transcripts
(hgvs_nucleotide, hgvs_protein) = get_hgvs(gene_obj)
hgvs_c.append(hgvs_nucleotide)
hgvs_p.append(hgvs_protein)
if len(gene_symbols) == 1:
variant_obj["hgvs"] = hgvs_str(gene_symbols, hgvs_p, hgvs_c)
# populate variant predictions for display
variant_obj.update(predictions(variant_genes))
variants.append(variant_obj)
return {"variants": variants, "more_variants": more_variants}
def test_gene_predictions_one_gene_no_sift():
## GIVEN a list with one gene and some missing values
gene = {
"hgnc_symbol": "AAA",
"polyphen_prediction": "probably_damaging",
"region_annotation": "exonic",
"functional_annotation": "missense_variant",
"spliceai_score": 0.17,
"spliceai_prediction": ["ds 0.17"],
}
genes = [gene]
## WHEN parsing the gene predictions
res = predictions(genes)
## THEN assert the result is correctly filled
assert res == {
"sift_predictions": ["-"],
"polyphen_predictions": ["probably_damaging"],
"region_annotations": ["exonic"],
"functional_annotations": ["missense_variant"],
"spliceai_scores": [0.17],
"spliceai_positions": ["-"],
"spliceai_predictions": [["ds 0.17"]],
}
def parse_variant(
store,
institute_obj,
case_obj,
variant_obj,
update=False,
genome_build="37",
get_compounds=True,
):
"""Parse information about variants.
- Adds information about compounds
- Updates the information about compounds if necessary and 'update=True'
Args:
store(scout.adapter.MongoAdapter)
institute_obj(scout.models.Institute)
case_obj(scout.models.Case)
variant_obj(scout.models.Variant)
update(bool): If variant should be updated in database
genome_build(str)
"""
has_changed = False
compounds = variant_obj.get("compounds", [])
if compounds and get_compounds:
# Check if we need to add compound information
# If it is the first time the case is viewed we fill in some compound information
if "not_loaded" not in compounds[0]:
new_compounds = store.update_variant_compounds(variant_obj)
variant_obj["compounds"] = new_compounds
has_changed = True
# sort compounds on combined rank score
variant_obj["compounds"] = sorted(
variant_obj["compounds"],
key=lambda compound: -compound["combined_score"])
# Update the hgnc symbols if they are incorrect
variant_genes = variant_obj.get("genes")
if variant_genes is not None:
for gene_obj in variant_genes:
# If there is no hgnc id there is nothin we can do
if not gene_obj["hgnc_id"]:
continue
# Else we collect the gene object and check the id
if gene_obj.get("hgnc_symbol") is None:
hgnc_gene = store.hgnc_gene(gene_obj["hgnc_id"],
build=genome_build)
if not hgnc_gene:
continue
has_changed = True
gene_obj["hgnc_symbol"] = hgnc_gene["hgnc_symbol"]
# We update the variant if some information was missing from loading
# Or if symbold in reference genes have changed
if update and has_changed:
variant_obj = store.update_variant(variant_obj)
variant_obj["comments"] = store.events(
institute_obj,
case=case_obj,
variant_id=variant_obj["variant_id"],
comments=True,
)
if variant_genes:
variant_obj.update(predictions(variant_genes))
if variant_obj.get("category") == "cancer":
variant_obj.update(get_variant_info(variant_genes))
for compound_obj in compounds:
compound_obj.update(predictions(compound_obj.get("genes", [])))
classification = variant_obj.get("acmg_classification")
if isinstance(classification, int):
acmg_code = ACMG_MAP[variant_obj["acmg_classification"]]
variant_obj["acmg_classification"] = ACMG_COMPLETE_MAP[acmg_code]
# convert length for SV variants
variant_length = variant_obj.get("length")
variant_obj["length"] = {
100000000000: "inf",
-1: "n.d."
}.get(variant_length, variant_length)
if not "end_chrom" in variant_obj:
variant_obj["end_chrom"] = variant_obj["chromosome"]
return variant_obj
def gene_variants(store, variants_query, institute_id, page=1, per_page=50):
"""Pre-process list of variants."""
# We need to call variants_collection.count_documents here
variant_count = variants_query.count()
skip_count = per_page * max(page - 1, 0)
more_variants = True if variant_count > (skip_count + per_page) else False
variant_res = variants_query.skip(skip_count).limit(per_page)
my_institutes = set(inst["_id"]
for inst in user_institutes(store, current_user))
variants = []
for variant_obj in variant_res:
# Populate variant case_display_name
variant_case_obj = store.case(case_id=variant_obj["case_id"])
if not variant_case_obj:
# A variant with missing case was encountered
continue
case_display_name = variant_case_obj.get("display_name")
variant_obj["case_display_name"] = case_display_name
# hide other institutes for now
other_institutes = set([variant_case_obj.get("owner")])
other_institutes.update(set(variant_case_obj.get("collaborators", [])))
if my_institutes.isdisjoint(other_institutes):
# If the user does not have access to the information we skip it
continue
genome_build = variant_case_obj.get("genome_build", "37")
if genome_build not in ["37", "38"]:
genome_build = "37"
# Update the HGNC symbols if they are not set
variant_genes = variant_obj.get("genes")
if variant_genes is not None:
for gene_obj in variant_genes:
# If there is no hgnc id there is nothin we can do
if not gene_obj["hgnc_id"]:
continue
# Else we collect the gene object and check the id
if (gene_obj.get("hgnc_symbol") is None
or gene_obj.get("description") is None):
hgnc_gene = store.hgnc_gene(gene_obj["hgnc_id"],
build=genome_build)
if not hgnc_gene:
continue
gene_obj["hgnc_symbol"] = hgnc_gene["hgnc_symbol"]
gene_obj["description"] = hgnc_gene["description"]
# Populate variant HGVS and predictions
gene_ids = []
gene_symbols = []
hgvs_c = []
hgvs_p = []
variant_genes = variant_obj.get("genes")
if variant_genes is not None:
functional_annotation = ""
for gene_obj in variant_genes:
hgnc_id = gene_obj["hgnc_id"]
gene_symbol = gene(store, hgnc_id)["symbol"]
gene_ids.append(hgnc_id)
gene_symbols.append(gene_symbol)
hgvs_nucleotide = "-"
# gather HGVS info from gene transcripts
transcripts_list = gene_obj.get("transcripts")
for transcript_obj in transcripts_list:
if (transcript_obj.get("is_canonical")
and transcript_obj.get("is_canonical") is True):
hgvs_nucleotide = str(
transcript_obj.get("coding_sequence_name"))
hgvs_protein = str(
transcript_obj.get("protein_sequence_name"))
hgvs_c.append(hgvs_nucleotide)
hgvs_p.append(hgvs_protein)
if len(gene_symbols) == 1:
if hgvs_p[0] != "None":
hgvs = hgvs_p[0]
elif hgvs_c[0] != "None":
hgvs = hgvs_c[0]
else:
hgvs = "-"
variant_obj["hgvs"] = hgvs
# populate variant predictions for display
variant_obj.update(predictions(variant_genes))
variants.append(variant_obj)
return {"variants": variants, "more_variants": more_variants}
