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Fix hotspot annotation #105

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Oct 30, 2020
+43 −58
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Fix hotspot annotation #105

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101 changes: 43 additions & 58 deletions AnnotatorCore.py
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Original file line number Diff line number Diff line change
Expand Up @@ -219,22 +219,12 @@ def getcuratedgenes():
log.error("error when processing %s \n" % url +
"reason: %s" % response.reason)

missensesinglehotspots = None
indelsinglehotspots = None
_3dhotspots = None
curatedgenes = []

def inithotspots():
global missensesinglehotspots
global indelsinglehotspots
def init_3d_hotspots():
global _3dhotspots
global curatedgenes
missensesinglehotspots = gethotspots(cancerhotspotsbaseurl+"/api/hotspots/single", "single residue")
indelsinglehotspots = gethotspots(cancerhotspotsbaseurl+"/api/hotspots/single", "in-frame indel")
_3dhotspots = gethotspots(_3dhotspotsbaseurl+"/api/hotspots/3d", None)
curatedgenes |= set(missensesinglehotspots.keys())
curatedgenes |= set(indelsinglehotspots.keys())
curatedgenes |= set(_3dhotspots.keys())


conversiondict = {'Ala': 'A',
Expand Down Expand Up @@ -356,7 +346,7 @@ def get_reference_genome_from_row(row_reference_genome, default_reference_genome
def processalterationevents(eventfile, outfile, previousoutfile, defaultCancerType, cancerTypeMap,
retainonlycuratedgenes, annotatehotspots, user_input_query_type, default_reference_genome):
if annotatehotspots:
inithotspots()
init_3d_hotspots()
if os.path.isfile(previousoutfile):
cacheannotated(previousoutfile, defaultCancerType, cancerTypeMap)
outf = open(outfile, 'w+', 1000)
Expand All @@ -371,8 +361,8 @@ def processalterationevents(eventfile, outfile, previousoutfile, defaultCancerTy
outf.write(headers['^-$'])

if annotatehotspots:
outf.write("\tis-a-hotspot")
outf.write("\tis-a-3d-hotspot")
outf.write("\tIS-A-HOTSPOT")
outf.write("\tIS-A-3D-HOTSPOT")
newncols += 2

outf.write("\t" + GENE_IN_ONCOKB_HEADER)
Expand Down Expand Up @@ -407,10 +397,10 @@ def processalterationevents(eventfile, outfile, previousoutfile, defaultCancerTy

if (query_type == QueryType.HGVSG):
process_hvsg(reader, outf, headers, [HGVSG_HEADER, ALTERATION_HEADER], ncols, newncols, defaultCancerType,
cancerTypeMap, default_reference_genome)
cancerTypeMap, annotatehotspots, default_reference_genome)

if (query_type == QueryType.GENOMIC_CHANGE):
process_genomic_change(reader, outf, headers, ncols, newncols, defaultCancerType, cancerTypeMap, default_reference_genome)
process_genomic_change(reader, outf, headers, ncols, newncols, defaultCancerType, cancerTypeMap, annotatehotspots, default_reference_genome)

outf.close()

Expand Down Expand Up @@ -489,30 +479,27 @@ def process_alteration(maffilereader, outf, maf_headers, alteration_column_names
if start is not None and end is None:
end = start

if annotatehotspots:
hotspot = pullsinglehotspots(hugo, hgvs, None, consequence, start, end, cancertype)
row.append(hotspot)

_3dhotspot = pull3dhotspots(hugo, hgvs, None, consequence, start, end, cancertype)
row.append(_3dhotspot)

if not retainonlycuratedgenes or hugo in curatedgenes:
query = ProteinChangeQuery(hugo, hgvs, cancertype, reference_genome, consequence, start, end)
queries.append(query)
rows.append(row)
else:
# Include Gene in OncoKB and Variant in OncoKB
if annotatehotspots:
default_cols = [['', '', GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]]
else:
default_cols = [[GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]]
append_annotation_to_file(outf, ncols + nannotationcols, [row],
[[GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]])
default_cols)

if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_protein_change_info(queries)
annotations = pull_protein_change_info(queries,annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
queries = []
rows = []

if len(queries) > 0:
annotations = pull_protein_change_info(queries)
annotations = pull_protein_change_info(queries,annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)

# this method is from genome-nexus annotation-tools
Expand All @@ -529,7 +516,7 @@ def get_var_allele(ref_allele, tumor_seq_allele1, tumor_seq_allele2):

return tumor_seq_allele

def process_genomic_change(maffilereader, outf, maf_headers, ncols, nannotationcols, defaultCancerType, cancerTypeMap, default_reference_genome):
def process_genomic_change(maffilereader, outf, maf_headers, ncols, nannotationcols, defaultCancerType, cancerTypeMap, annotatehotspots, default_reference_genome):
ichromosome = geIndexOfHeader(maf_headers, [GC_CHROMOSOME_HEADER])
istart = geIndexOfHeader(maf_headers, [GC_START_POSITION_HEADER])
iend = geIndexOfHeader(maf_headers, [GC_END_POSITION_HEADER])
Expand Down Expand Up @@ -574,16 +561,16 @@ def process_genomic_change(maffilereader, outf, maf_headers, ncols, nannotationc
rows.append(row)

if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_genomic_change_info(queries)
annotations = pull_genomic_change_info(queries,annotatehotspots)
append_annotation_to_file(outf, ncols+nannotationcols, rows, annotations)
queries = []
rows = []

if len(queries) > 0:
annotations = pull_genomic_change_info(queries)
annotations = pull_genomic_change_info(queries,annotatehotspots)
append_annotation_to_file(outf, ncols+nannotationcols, rows, annotations)

def process_hvsg(maffilereader, outf, maf_headers, alteration_column_names, ncols, nannotationcols, defaultCancerType, cancerTypeMap, default_reference_genome):
def process_hvsg(maffilereader, outf, maf_headers, alteration_column_names, ncols, nannotationcols, defaultCancerType, cancerTypeMap, annotatehotspots, default_reference_genome):
ihgvsg = geIndexOfHeader(maf_headers, alteration_column_names)
isample = geIndexOfHeader(maf_headers, SAMPLE_HEADERS)
icancertype = geIndexOfHeader(maf_headers, CANCER_TYPE_HEADERS)
Expand All @@ -610,21 +597,25 @@ def process_hvsg(maffilereader, outf, maf_headers, alteration_column_names, ncol
reference_genome = get_reference_genome_from_row(get_cell_content(row, ireferencegenome), default_reference_genome)

if hgvsg is None:
if annotatehotspots:
default_cols = [['', '', GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]]
else:
default_cols = [[GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]]
append_annotation_to_file(outf, ncols + nannotationcols, [row],
[[GENE_IN_ONCOKB_DEFAULT, VARIANT_IN_ONCOKB_DEFAULT]])
default_cols)
else:
query = HGVSgQuery(hgvsg, cancertype, reference_genome)
queries.append(query)
rows.append(row)

if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_hgvsg_info(queries)
annotations = pull_hgvsg_info(queries, annotatehotspots)
append_annotation_to_file(outf, ncols+nannotationcols, rows, annotations)
queries = []
rows = []

if len(queries) > 0:
annotations = pull_hgvsg_info(queries)
annotations = pull_hgvsg_info(queries,annotatehotspots)
append_annotation_to_file(outf, ncols+nannotationcols, rows, annotations)


Expand Down Expand Up @@ -1175,22 +1166,7 @@ def geIndexOfHeader(headers, keywords):
return -1


def pullsinglehotspots(hugo, proteinchange, alterationtype, consequence, start, end, cancertype):
try:
if hugo in missensesinglehotspots and consequence == "missense_variant":
for i in range(int(start), int(end) + 1):
if i in missensesinglehotspots[hugo]:
return "Y"
if hugo in indelsinglehotspots and (consequence == "inframe_insertion" or consequence == "inframe_deletion"):
for i in range(int(start), int(end) + 1):
if i in indelsinglehotspots[hugo]:
return "Y"
except TypeError:
log.error("%s: %s-%s" % (hugo, str(start), str(end)))
return ""


def pull3dhotspots(hugo, proteinchange, alterationtype, consequence, start, end, cancertype):
def pull3dhotspots(hugo, consequence, start, end):
try:
if hugo in _3dhotspots and consequence == "missense_variant":
for i in range(int(start), int(end) + 1):
Expand Down Expand Up @@ -1275,7 +1251,7 @@ def __init__(self, hugoA, hugoB, structural_variant_type, cancertype):
self.tumorType = cancertype


def pull_protein_change_info(queries):
def pull_protein_change_info(queries, annotate_hotspot):
url = oncokbapiurl + '/annotate/mutations/byProteinChange'
response = makeoncokbpostrequest(url, queries)
annotation = []
Expand Down Expand Up @@ -1303,11 +1279,11 @@ def pull_protein_change_info(queries):

processed_annotation = []
for query_annotation in annotation:
processed_annotation.append(process_oncokb_annotation(query_annotation))
processed_annotation.append(process_oncokb_annotation(query_annotation, annotate_hotspot))
return processed_annotation


def pull_hgvsg_info(queries):
def pull_hgvsg_info(queries, annotate_hotspot):
url = oncokbapiurl + '/annotate/mutations/byHGVSg'
response = makeoncokbpostrequest(url, queries)
annotation = []
Expand All @@ -1328,10 +1304,10 @@ def pull_hgvsg_info(queries):

processed_annotation = []
for query_annotation in annotation:
processed_annotation.append(process_oncokb_annotation(query_annotation))
processed_annotation.append(process_oncokb_annotation(query_annotation, annotate_hotspot))
return processed_annotation

def pull_genomic_change_info(queries):
def pull_genomic_change_info(queries, annotate_hotspot):
url = oncokbapiurl + '/annotate/mutations/byGenomicChange'
response = makeoncokbpostrequest(url, queries)
annotation = []
Expand All @@ -1352,7 +1328,7 @@ def pull_genomic_change_info(queries):

processed_annotation = []
for query_annotation in annotation:
processed_annotation.append(process_oncokb_annotation(query_annotation))
processed_annotation.append(process_oncokb_annotation(query_annotation, annotate_hotspot))
return processed_annotation


Expand All @@ -1379,7 +1355,7 @@ def pull_cna_info(queries):

processed_annotation = []
for query_annotation in annotation:
processed_annotation.append(process_oncokb_annotation(query_annotation))
processed_annotation.append(process_oncokb_annotation(query_annotation, annotate_hotspot=False))
return processed_annotation


Expand Down Expand Up @@ -1410,12 +1386,12 @@ def pull_structural_variant_info(queries):

processed_annotation = []
for query_annotation in annotation:
processed_annotation.append(process_oncokb_annotation(query_annotation))
processed_annotation.append(process_oncokb_annotation(query_annotation, annotate_hotspot=False))
return processed_annotation



def process_oncokb_annotation(annotation):
def process_oncokb_annotation(annotation, annotate_hotspot):
if annotation is None:
return None

Expand Down Expand Up @@ -1476,6 +1452,15 @@ def process_oncokb_annotation(annotation):


ret = []
if annotate_hotspot:
if annotation['hotspot']:
ret.append('Y')
else:
ret.append('')

_3dhotspot = pull3dhotspots(annotation['query']['hugoSymbol'], annotation['query']['consequence'], annotation['query']['proteinStart'], annotation['query']['proteinEnd'])
ret.append(_3dhotspot)

ret.append(oncokbdata[GENE_IN_ONCOKB_HEADER])
ret.append(oncokbdata[VARIANT_IN_ONCOKB_HEADER])
ret.append(oncokbdata['mutation_effect'])
Expand Down