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feat!: change Genie fusion detection algorithm input parameters (#210)
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@jarbesfeld
jarbesfeld authored Dec 3, 2024
1 parent 9ebda76 commit d143d94
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Showing 2 changed files with 109 additions and 75 deletions.
108 changes: 66 additions & 42 deletions src/fusor/translator.py
View file
Original file line number Diff line number Diff line change
Expand Up @@ -128,7 +128,7 @@ def _get_gene_element(self, genes: str, caller: Caller) -> GeneElement:
"""
if "," not in genes or caller != caller.ARRIBA:
ge = self.fusor.gene_element(gene=genes)
return ge if ge[0] else self._get_gene_element_unnormalized(genes)
return ge[0] if ge[0] else self._get_gene_element_unnormalized(genes)

genes = genes.split(",")
dists = []
Expand All @@ -139,7 +139,7 @@ def _get_gene_element(self, genes: str, caller: Caller) -> GeneElement:
genes[0].split("(")[0] if dists[0] <= dists[1] else genes[1].split("(")[0]
)
ge = self.fusor.gene_element(gene=gene)
return ge if ge[0] else self._get_gene_element_unnormalized(gene)
return ge[0] if ge[0] else self._get_gene_element_unnormalized(gene)

def _get_genomic_ac(self, chrom: str, build: Assembly) -> str:
"""Return a RefSeq genomic accession given a chromosome and a reference build
Expand Down Expand Up @@ -185,8 +185,8 @@ async def from_jaffa(
:return: An AssayedFusion object, if construction is successful
"""
genes = fusion_genes.split(":")
gene_5prime_element = self._get_gene_element(genes[0], Caller.JAFFA)[0]
gene_3prime_element = self._get_gene_element(genes[1], Caller.JAFFA)[0]
gene_5prime_element = self._get_gene_element(genes[0], Caller.JAFFA)
gene_3prime_element = self._get_gene_element(genes[1], Caller.JAFFA)
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

Expand Down Expand Up @@ -239,8 +239,8 @@ async def from_star_fusion(
"""
gene1 = left_gene.split("^")[0]
gene2 = right_gene.split("^")[0]
gene_5prime_element = self._get_gene_element(gene1, Caller.STAR_FUSION)[0]
gene_3prime_element = self._get_gene_element(gene2, Caller.STAR_FUSION)[0]
gene_5prime_element = self._get_gene_element(gene1, Caller.STAR_FUSION)
gene_3prime_element = self._get_gene_element(gene2, Caller.STAR_FUSION)
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

Expand Down Expand Up @@ -292,10 +292,10 @@ async def from_fusion_catcher(
"""
gene_5prime_element = self._get_gene_element(
five_prime_partner, Caller.FUSION_CATCHER
)[0]
)
gene_3prime_element = self._get_gene_element(
three_prime_partner, Caller.FUSION_CATCHER
)[0]
)

five_prime = five_prime_fusion_point.split(":")
three_prime = three_prime_fusion_point.split(":")
Expand Down Expand Up @@ -332,8 +332,8 @@ async def from_fusion_map(
"""
gene1 = fmap_row.get_column("KnownGene1").item()
gene2 = fmap_row.get_column("KnownGene2").item()
gene_5prime = self._get_gene_element(gene1, "fusion_map")[0].gene.label
gene_3prime = self._get_gene_element(gene2, "fusion_map")[0].gene.label
gene_5prime = self._get_gene_element(gene1, "fusion_map").gene.label
gene_3prime = self._get_gene_element(gene2, "fusion_map").gene.label

tr_5prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
Expand Down Expand Up @@ -409,16 +409,18 @@ async def from_arriba(
# Arriba reports two gene symbols if a breakpoint occurs in an intergenic
# space. We select the gene symbol with the smallest distance from the
# breakpoint.
gene_5prime = self._get_gene_element(gene1, "arriba")[0].gene.label
gene_3prime = self._get_gene_element(gene2, "arriba")[0].gene.label
gene_5prime_element = self._get_gene_element(gene1, "arriba")
gene_3prime_element = self._get_gene_element(gene2, "arriba")
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

strand1 = strand1.split("/")[1] # Determine strand that is transcribed
strand2 = strand2.split("/")[1] # Determine strand that is transcribed
if strand1 == "-":
if strand1 == "+":
gene1_seg_start = direction1 == "upstream"
else:
gene1_seg_start = direction1 == "downstream"
if strand2 == "-":
if strand2 == "+":
gene2_seg_start = direction2 == "upstream"
else:
gene2_seg_start = direction2 == "downstream"
Expand Down Expand Up @@ -457,7 +459,7 @@ async def from_arriba(
)
rf = bool(rf == "in-frame") if rf != "." else None
return self._format_fusion(
gene_5prime, gene_3prime, tr_5prime, tr_3prime, ce, rf
gene_5prime_element, gene_3prime_element, tr_5prime, tr_3prime, ce, rf
)

async def from_cicero(
Expand Down Expand Up @@ -502,8 +504,10 @@ async def from_cicero(
_logger.warning(msg)
return msg

gene_5prime = self._get_gene_element(gene_5prime, "cicero")[0].gene.label
gene_3prime = self._get_gene_element(gene_3prime, "cicero")[0].gene.label
gene_5prime_element = self._get_gene_element(gene_5prime, "cicero")
gene_3prime_element = self._get_gene_element(gene_3prime, "cicero")
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

tr_5prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
Expand Down Expand Up @@ -532,8 +536,8 @@ async def from_cicero(
eventDescription=event_type,
)
return self._format_fusion(
gene_5prime,
gene_3prime,
gene_5prime_element,
gene_3prime_element,
tr_5prime,
tr_3prime,
ce,
Expand All @@ -550,8 +554,10 @@ async def from_mapsplice(
"""
gene1 = mapsplice_row[60].strip(",")
gene2 = mapsplice_row[61].strip(",")
gene_5prime = self._get_gene_element(gene1, "mapsplice")[0].gene.label
gene_3prime = self._get_gene_element(gene2, "mapsplice")[0].gene.label
gene_5prime_element = self._get_gene_element(gene1, "mapsplice")
gene_3prime_element = self._get_gene_element(gene2, "mapsplice")
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

tr_5prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
Expand Down Expand Up @@ -595,8 +601,10 @@ async def from_enfusion(
:param rb: The reference build used to call the fusion
:return: An AssayedFusion object, if construction is successful
"""
gene_5prime = self._get_gene_element(gene_5prime, "enfusion")[0].gene.label
gene_3prime = self._get_gene_element(gene_3prime, "enfusion")[0].gene.label
gene_5prime_element = self._get_gene_element(gene_5prime, "enfusion")
gene_3prime_element = self._get_gene_element(gene_3prime, "enfusion")
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

tr_5prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
Expand All @@ -618,46 +626,62 @@ async def from_enfusion(
chr_5prime,
chr_3prime,
)
return self._format_fusion(gene_5prime, gene_3prime, tr_5prime, tr_3prime, ce)
return self._format_fusion(
gene_5prime_element, gene_3prime_element, tr_5prime, tr_3prime, ce
)

async def from_genie(self, genie_row: pl.DataFrame, rb: Assembly) -> AssayedFusion:
async def from_genie(
self,
site1_hugo: str,
site2_hugo: str,
site1_chrom: int,
site2_chrom: int,
site1_pos: int,
site2_pos: int,
annot: str,
reading_frame: str,
rb: Assembly,
) -> AssayedFusion:
"""Parse GENIE output to create AssayedFusion object
:param genie_row: A row of EnFusion output
:param site1_hugo: The HUGO symbol reported at site 1
:param site2_hugo: The HUGO symbol reported at site 2
:param site1_chrom: The chromosome reported at site 1
:param site2_chrom: The chromosome reported at site 2
:param site1_pos: The breakpoint reported at site 1
:param site2_pos: The breakpoint reported at site 2
:param annot: The annotation for the fusion event
:param reading_frame: The reading frame status of the fusion
:param rb: The reference build used to call the fusion
:return: An AssayedFusion object, if construction is successful
"""
gene1 = genie_row.get_column("Site1_Hugo_Symbol").item()
gene2 = genie_row.get_column("Site2_Hugo_Symbol").item()
gene_5prime = self._get_gene_element(gene1, "genie")[0].gene.label
gene_3prime = self._get_gene_element(gene2, "genie")[0].gene.label
gene_5prime_element = self._get_gene_element(site1_hugo, "genie")
gene_3prime_element = self._get_gene_element(site2_hugo, "genie")
gene_5prime = gene_5prime_element.gene.label
gene_3prime = gene_3prime_element.gene.label

tr_5prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
genomic_ac=self._get_genomic_ac(
genie_row.get_column("Site1_Chromosome").item(), rb
),
seg_end_genomic=int(genie_row.get_column("Site1_Position").item()),
genomic_ac=self._get_genomic_ac(site1_chrom, rb),
seg_end_genomic=site1_pos,
gene=gene_5prime,
get_nearest_transcript_junction=True,
)

tr_3prime = await self.fusor.transcript_segment_element(
tx_to_genomic_coords=False,
genomic_ac=self._get_genomic_ac(
genie_row.get_column("Site2_Chromosome").item(), rb
),
seg_start_genomic=int(genie_row.get_column("Site2_Position").item()),
genomic_ac=self._get_genomic_ac(site2_chrom, rb),
seg_start_genomic=site2_pos,
gene=gene_3prime,
get_nearest_transcript_junction=True,
)

ce = self._get_causative_event(
genie_row.get_column("Site1_Chromosome").item(),
genie_row.get_column("Site2_Chromosome").item(),
genie_row.get_column("Annotation").item(),
site1_chrom,
site2_chrom,
annot,
)
rf = bool(genie_row.get_column("Site2_Effect_on_Frame").item() == "in frame")
rf = bool(reading_frame == "in frame")
return self._format_fusion(
gene_5prime, gene_3prime, tr_5prime, tr_3prime, ce, rf
)
76 changes: 43 additions & 33 deletions tests/test_translators.py
View file
Original file line number Diff line number Diff line change
Expand Up @@ -112,7 +112,7 @@ def test_gene_element_arriba(translator_instance):
"""Test gene selection for Arriba"""
genes = "RP1-222H5.1(151985),MIR3672(13973)"
gene = translator_instance._get_gene_element(genes=genes, caller=Caller.ARRIBA)
assert gene[0].gene.label == "MIR3672"
assert gene.gene.label == "MIR3672"


@pytest.mark.asyncio()
Expand Down Expand Up @@ -177,7 +177,7 @@ async def test_star_fusion(
right_gene = "PDGFRB^ENSG00000113721"
left_breakpoint = "chr1:154170465:-"
right_breakpoint = "chr5:150126612:-"
annots = '["INTRACHROMOSOMAL[chr16:0.23Mb]"]'
annots = '["INTERCHROMOSOMAL]'

star_fusion_fusor = await translator_instance.from_star_fusion(
left_gene,
Expand All @@ -194,7 +194,7 @@ async def test_star_fusion(
right_gene = "PDGFRB^ENSG00000113721"
left_breakpoint = "chr1:154173078:-"
right_breakpoint = "chr5:150127173:-"
annots = '["INTRACHROMOSOMAL[chr16:0.23Mb]"]'
annots = '["INTERCHROMOSOMAL]'

star_fusion_fusor_nonexonic = await translator_instance.from_star_fusion(
left_gene,
Expand Down Expand Up @@ -312,8 +312,8 @@ async def test_arriba(
breakpoint2 = "5:150126612"
event = "translocation"
confidence = "high"
direction1 = "dowstream"
direction2 = "upstream"
direction1 = "upstream"
direction2 = "downstream"
rf = "in-frame"

arriba_fusor = await translator_instance.from_arriba(
Expand Down Expand Up @@ -341,8 +341,8 @@ async def test_arriba(
breakpoint2 = "5:150127173"
event = "translocation"
confidence = "high"
direction1 = "dowstream"
direction2 = "upstream"
direction1 = "upstream"
direction2 = "downstream"
rf = "in-frame"

arriba_fusor_nonexonic = await translator_instance.from_arriba(
Expand Down Expand Up @@ -516,37 +516,47 @@ async def test_genie(
):
"""Test GENIE Translator"""
# Test exonic breakpoint
genie_data = pl.DataFrame(
{
"Site1_Hugo_Symbol": "TPM3",
"Site2_Hugo_Symbol": "PDGFRB",
"Site1_Chromosome": "1",
"Site1_Position": "154170465",
"Site2_Chromosome": "5",
"Site2_Position": "150126612",
"Annotation": "TMP3 (NM_152263.4) - PDGFRB (NM_002609.4) fusion",
"Site2_Effect_on_Frame": "In_frame",
}
)
site1_hugo = "TPM3"
site2_hugo = "PDGFRB"
site1_chrom = 1
site2_chrom = 5
site1_pos = 154170465
site2_pos = 150126612
annot = "TMP3 (NM_152263.4) - PDGFRB (NM_002609.4) fusion"
reading_frame = "In_frame"

genie_fusor = await translator_instance.from_genie(
genie_data, Assembly.GRCH38.value
site1_hugo,
site2_hugo,
site1_chrom,
site2_chrom,
site1_pos,
site2_pos,
annot,
reading_frame,
Assembly.GRCH38.value,
)
assert genie_fusor.structure == fusion_data_example.structure

# Test non-exonic breakpoint
genie_data_nonexonic = pl.DataFrame(
{
"Site1_Hugo_Symbol": "TPM3",
"Site2_Hugo_Symbol": "PDGFRB",
"Site1_Chromosome": "1",
"Site1_Position": "154173078",
"Site2_Chromosome": "5",
"Site2_Position": "150127173",
"Annotation": "TMP3 (NM_152263.4) - PDGFRB (NM_002609.4) fusion",
"Site2_Effect_on_Frame": "In_frame",
}
)
site1_hugo = "TPM3"
site2_hugo = "PDGFRB"
site1_chrom = 1
site2_chrom = 5
site1_pos = 154173078
site2_pos = 150127173
annot = "TMP3 (NM_152263.4) - PDGFRB (NM_002609.4) fusion"
reading_frame = "In_frame"

genie_fusor_nonexonic = await translator_instance.from_genie(
genie_data_nonexonic, Assembly.GRCH38.value
site1_hugo,
site2_hugo,
site1_chrom,
site2_chrom,
site1_pos,
site2_pos,
annot,
reading_frame,
Assembly.GRCH38.value,
)
assert genie_fusor_nonexonic.structure == fusion_data_example_nonexonic.structure

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