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Implement duplication - tandem setting to temporary fix the PVS1 criteria for duplication CNVs #205

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merged 1 commit into from
Sep 10, 2024
Merged

Implement duplication - tandem setting to temporary fix the PVS1 criteria for duplication CNVs #205

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4 changes: 2 additions & 2 deletions src/auto_acmg.py
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Original file line number Diff line number Diff line change
Expand Up @@ -488,7 +488,7 @@ def predict(self) -> Union[AutoACMGSeqVarResult, AutoACMGStrucVarResult, None]:
predictor_class = self.select_predictor(self.seqvar_result.data.hgnc_id)
predictor = predictor_class(self.seqvar, self.seqvar_result, self.config)
seqvar_prediction = predictor.predict()
logger.info("Prediction: {}", seqvar_prediction)
# logger.info("Prediction: {}", seqvar_prediction)
return seqvar_prediction

elif isinstance(self.strucvar, StrucVar):
Expand All @@ -501,7 +501,7 @@ def predict(self) -> Union[AutoACMGSeqVarResult, AutoACMGStrucVarResult, None]:
# ====== Predict ======
sp = DefaultStrucVarPredictor(self.strucvar, self.strucvar_result, self.config)
strucvar_prediction = sp.predict()
# logger.info("Prediction: {}", strucvar_prediction)
logger.info("Prediction: {}", strucvar_prediction)
return strucvar_prediction

else:
Expand Down
15 changes: 14 additions & 1 deletion src/cli.py
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Expand Up @@ -5,6 +5,7 @@
from typing_extensions import Annotated

from src.auto_acmg import AutoACMG
from src.core.config import settings
from src.defs.exceptions import AutoAcmgBaseException, InvalidGenomeBuild
from src.defs.genome_builds import GenomeRelease

Expand Down Expand Up @@ -38,6 +39,17 @@ def classify(
help=f"Accepted genome Releases: {', '.join(ALLOWED_GENOME_RELEASES)}",
),
] = "GRCh38",
duplication_tandem: Annotated[
bool,
typer.Option(
"--duplication-tandem",
"-dt",
help=(
"Flag to indicate if the duplication is in tandem AND disrupts reading frame AND "
"undergoes NMD."
),
),
] = False,
):
"""
Classify sequence variant on the ACMG guidelines.
Expand All @@ -52,7 +64,8 @@ def classify(
)
)
raise InvalidGenomeBuild("Invalid genome release")

# Temporary save the duplication tandem flag in the settings
settings.DUPLICATION_TANDEM = duplication_tandem
auto_acmg = AutoACMG(variant, genome_release_enum)
prediction = auto_acmg.predict()
prediction.save_to_file() if prediction else logger.error("No prediction was made.")
Expand Down
5 changes: 5 additions & 0 deletions src/core/config.py
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Expand Up @@ -39,6 +39,11 @@ class Settings(BaseSettings):
#: Username for genebe
GENEBE_USERNAME: str = ""

# ==== Temporary settings ===

#: Flag to indicate if the duplication is in tandem AND disrupts reading frame AND undergoes NMD
DUPLICATION_TANDEM: bool = False

#: Path to the root directory
@property
def PATH_TO_ROOT(self) -> str:
Expand Down
80 changes: 55 additions & 25 deletions src/strucvar/auto_pvs1.py
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Expand Up @@ -4,6 +4,7 @@

from loguru import logger

from src.core.config import settings
from src.defs.auto_acmg import (
AutoACMGCriteria,
AutoACMGPrediction,
Expand Down Expand Up @@ -577,17 +578,26 @@ def lof_rm_gt_10pct_of_prot(

@staticmethod
def dup_disrupt_rf() -> bool:
"""Check if the duplication disrupts the reading frame."""
"""
Check if the duplication disrupts the reading frame.
NOT IMPLEMENTED!
"""
return False

@staticmethod
def proven_in_tandem() -> bool:
"""Check if the duplication is proven in tandem."""
"""
Check if the duplication is proven in tandem.
NOT IMPLEMENTED!
"""
return False

@staticmethod
def presumed_in_tandem() -> bool:
"""Check if the duplication is presumed in tandem."""
"""
Check if the duplication is presumed in tandem.
NOT IMPLEMENTED!
"""
return False


Expand Down Expand Up @@ -683,31 +693,51 @@ def verify_pvs1( # pragma: no cover
self.prediction_path = PVS1PredictionStrucVarPath.DEL7_2

elif strucvar.sv_type == StrucVarType.DUP:
self.comment_pvs1 = "Analysing the duplication variant. => "
if self.proven_in_tandem():
self.comment_pvs1 += " =>"
if self.dup_disrupt_rf() and self.undergo_nmd(
strucvar, var_data.exons, var_data.strand
):
self.prediction = PVS1Prediction.PVS1
self.prediction_path = PVS1PredictionStrucVarPath.DUP1
else:
self.prediction = PVS1Prediction.NotPVS1
self.prediction_path = PVS1PredictionStrucVarPath.DUP2_1
elif self.presumed_in_tandem():
self.comment_pvs1 += " =>"
if self.dup_disrupt_rf() and self.undergo_nmd(
strucvar, var_data.exons, var_data.strand
):
self.prediction = PVS1Prediction.PVS1_Strong
self.prediction_path = PVS1PredictionStrucVarPath.DUP3
else:
self.prediction = PVS1Prediction.NotPVS1
self.prediction_path = PVS1PredictionStrucVarPath.DUP2_2
self.comment_pvs1 = (
"THE CRITERIA RELY ON THE DUPLICATION_TANDEM SETTING. "
"Please, specify the entry in CLI or API. Per default, the criteria is set to "
"False (Not PVS1). "
)
self.comment_pvs1 += "Analysing the duplication variant. => "

if settings.DUPLICATION_TANDEM:
self.comment_pvs1 += (
"The duplication is in tandem AND disrupts reading frame AND undergoes NMD. "
)
self.prediction = PVS1Prediction.PVS1
self.prediction_path = PVS1PredictionStrucVarPath.DUP1
else:
self.comment_pvs1 += (
"The duplication is not in tandem OR does not disrupt reading frame OR "
"does not undergo NMD."
)
self.prediction = PVS1Prediction.NotPVS1
self.prediction_path = PVS1PredictionStrucVarPath.DUP4
self.prediction_path = PVS1PredictionStrucVarPath.DUP3

# if self.proven_in_tandem():
# self.comment_pvs1 += " =>"
# if self.dup_disrupt_rf() and self.undergo_nmd(
# strucvar, var_data.exons, var_data.strand
# ):
# self.prediction = PVS1Prediction.PVS1
# self.prediction_path = PVS1PredictionStrucVarPath.DUP1
# else:
# self.prediction = PVS1Prediction.NotPVS1
# self.prediction_path = PVS1PredictionStrucVarPath.DUP2_1
# elif self.presumed_in_tandem():
# self.comment_pvs1 += " =>"
# if self.dup_disrupt_rf() and self.undergo_nmd(
# strucvar, var_data.exons, var_data.strand
# ):
# self.prediction = PVS1Prediction.PVS1_Strong
# self.prediction_path = PVS1PredictionStrucVarPath.DUP3
# else:
# self.prediction = PVS1Prediction.NotPVS1
# self.prediction_path = PVS1PredictionStrucVarPath.DUP2_2

# else:
# self.prediction = PVS1Prediction.NotPVS1
# self.prediction_path = PVS1PredictionStrucVarPath.DUP4

else:
self.prediction = PVS1Prediction.NotSet
Expand Down
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