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test_hgvs_assemblymapper.py
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# -*- coding: utf-8 -*-
import os
import unittest
import pytest
from support import CACHE
import hgvs.assemblymapper
import hgvs.dataproviders.uta
import hgvs.parser
import hgvs.variantmapper
from hgvs.enums import PrevalidationLevel
from hgvs.exceptions import HGVSInvalidVariantError
@pytest.mark.quick
class Test_VariantMapper(unittest.TestCase):
@classmethod
def setUpClass(cls):
cls.hdp = hgvs.dataproviders.uta.connect(
mode=os.environ.get("HGVS_CACHE_MODE", "run"), cache=CACHE
)
cls.am = hgvs.assemblymapper.AssemblyMapper(cls.hdp)
cls.am37 = hgvs.assemblymapper.AssemblyMapper(cls.hdp, assembly_name="GRCh37")
cls.hp = hgvs.parser.Parser()
def test_VariantMapper_quick(self):
# From garcia.tsv:
hgvs_g = "NC_000007.13:g.36561662C>T"
hgvs_c = "NM_001637.3:c.1582G>A"
hgvs_p = "NP_001628.1:p.(Gly528Arg)"
var_g = self.hp.parse_hgvs_variant(hgvs_g)
var_c = self.am.g_to_c(var_g, "NM_001637.3")
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_c), hgvs_c)
self.assertEqual(str(var_p), hgvs_p)
with self.assertRaises(HGVSInvalidVariantError):
self.am.c_to_p(self.hp.parse_hgvs_variant("NM_000059.3:c.7790delAAG"))
hgvs_c = "NM_000059.3:c.7791A>G"
hgvs_p = "NP_000050.2:p.(Lys2597=)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_000302.3:c.1594_1596del"
hgvs_p = "NP_000293.2:p.(Glu532del)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_000090.3:c.2490_2516del"
hgvs_p = "NP_000081.1:p.(Glu832_Gly840del)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_001292004.1:c.376="
hgvs_g = "NC_000005.10:g.74715659="
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_g = self.am.c_to_g(var_c)
self.assertEqual(str(var_g), hgvs_g)
hgvs_c = "NM_000116.4:c.-8_-3inv6"
hgvs_g = "NC_000023.11:g.154411836_154411841inv"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_g = self.am.c_to_g(var_c)
self.assertEqual(str(var_g), hgvs_g)
hgvs_c = "NM_000348.3:c.89_91inv3"
hgvs_g = "NC_000002.12:g.31580810_31580812inv"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_g = self.am.c_to_g(var_c)
self.assertEqual(str(var_g), hgvs_g)
hgvs_c = "NM_001637.3:c.1582_1583inv"
hgvs_p = "NP_001628.1:p.(Gly528Pro)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_025137.3:c.-20_*20inv"
hgvs_p = "NP_079413.3:p.?"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
def test_projection_at_alignment_discrepancy(self):
hgvs_g = "NC_000019.10:g.50378563_50378564insTG"
hgvs_n = "NM_007121.5:n.796_798delinsTG"
var_g = self.hp.parse_hgvs_variant(hgvs_g)
var_n = self.am.g_to_n(var_g, "NM_007121.5")
self.assertEqual(str(var_n), hgvs_n)
hgvs_g = "NC_000007.14:g.149779575delC"
hgvs_n = "NM_198455.2:n.1115_1116insAG"
var_g = self.hp.parse_hgvs_variant(hgvs_g)
var_n = self.am.g_to_n(var_g, "NM_198455.2")
self.assertEqual(str(var_n), hgvs_n)
# issue-353
hgvs_g = "NC_000012.11:g.122064775C>T"
hgvs_c = "NM_032790.3:c.127_128insTGCCAC"
var_g = self.hp.parse_hgvs_variant(hgvs_g)
var_c = self.am.g_to_c(var_g, "NM_032790.3")
self.assertEqual(str(var_c), hgvs_c)
# issue-461
hgvs_g = "NC_000002.11:g.73675227_73675228insCTC"
hgvs_c = "NM_015120.4:c.1574_1576="
var_g = self.hp.parse_hgvs_variant(hgvs_g)
var_c = self.am37.g_to_c(var_g, "NM_015120.4")
self.assertEqual(str(var_c), hgvs_c)
# issue-259
hgvs_c = "NM_000116.4:c.-120_-119insT"
hgvs_g = "NC_000023.10:g.153640061="
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_g = self.am37.c_to_g(var_c)
self.assertEqual(str(var_g), hgvs_g)
hgvs_c = "NM_000348.3:c.88del"
hgvs_g = "NC_000002.11:g.31805882_31805883="
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_g = self.am37.c_to_g(var_c)
self.assertEqual(str(var_g), hgvs_g)
def test_c_to_p_with_stop_gain(self):
# issue-474
hgvs_c = "NM_080877.2:c.1733_1735delinsTTT"
hgvs_p = "NP_543153.1:p.(Pro578_Lys579delinsLeuTer)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
# issue-492
hgvs_c = "NM_001034853.1:c.2847_2848delAGinsCT"
hgvs_p = "NP_001030025.1:p.(Glu949_Glu950delinsAspTer)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_001034853.1:c.2847_2848inv"
hgvs_p = "NP_001030025.1:p.(Glu949_Glu950delinsAspTer)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_080877.2:c.1735A>T"
hgvs_p = "NP_543153.1:p.(Lys579Ter)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
hgvs_c = "NM_080877.2:c.1795_*3delinsTAG"
hgvs_p = "NP_543153.1:p.(Leu599Ter)"
var_c = self.hp.parse_hgvs_variant(hgvs_c)
var_p = self.am.c_to_p(var_c)
self.assertEqual(str(var_p), hgvs_p)
class Test_RefReplacement(unittest.TestCase):
test_cases = [
# These casese attempt to test reference update in four dimensions:
# - variant type: n, c, g
# - major mapping paths: c<->n, c<->g, n<->g
# - variant class: sub, del, ins, delins, dup
# - strand: +/-
# ADRB2 │ NM_000024.5 │ 239 │ 1481 │ NC_000005.9 │ 1 │ 148206155,148208197 | 284=1X32=1X1724=
# cseq = hdp.fetch_seq("NM_000024.5")
# gseq = hdp.fetch_seq("NC_000005.9",148206155,148208197)
# cseq[280:290] = "CAATAGAAGC"
# gseq[280:290] = "CAATGGAAGC"
# ^ @ n.285
# These variants are in and around the first sub:
{
"c": "NM_000024.5:c.42C>N",
"g": "NC_000005.9:g.148206436C>N",
"n": "NM_000024.5:n.281C>N",
},
{
"c": "NM_000024.5:c.43A>N",
"g": "NC_000005.9:g.148206437A>N",
"n": "NM_000024.5:n.282A>N",
},
{
"c": "NM_000024.5:c.44A>N",
"g": "NC_000005.9:g.148206438A>N",
"n": "NM_000024.5:n.283A>N",
},
{
"c": "NM_000024.5:c.45T>N",
"g": "NC_000005.9:g.148206439T>N",
"n": "NM_000024.5:n.284T>N",
},
{
"c": "NM_000024.5:c.46A>N",
"g": "NC_000005.9:g.148206440G>N",
"n": "NM_000024.5:n.285A>N",
}, # ref repl
{
"c": "NM_000024.5:c.47G>N",
"g": "NC_000005.9:g.148206441G>N",
"n": "NM_000024.5:n.286G>N",
},
{
"c": "NM_000024.5:c.48A>N",
"g": "NC_000005.9:g.148206442A>N",
"n": "NM_000024.5:n.287A>N",
},
{
"c": "NM_000024.5:c.49A>N",
"g": "NC_000005.9:g.148206443A>N",
"n": "NM_000024.5:n.288A>N",
},
{
"c": "NM_000024.5:c.50G>N",
"g": "NC_000005.9:g.148206444G>N",
"n": "NM_000024.5:n.289G>N",
},
{
"c": "NM_000024.5:c.51C>N",
"g": "NC_000005.9:g.148206445C>N",
"n": "NM_000024.5:n.290C>N",
},
# ins, del, delins, dup:
{
"c": "NM_000024.5:c.46_47insNN",
"g": "NC_000005.9:g.148206440_148206441insNN",
"n": "NM_000024.5:n.285_286insNN",
},
{
"c": "NM_000024.5:c.45_47delTAG",
"g": "NC_000005.9:g.148206439_148206441delTGG",
"n": "NM_000024.5:n.284_286delTAG",
},
{
"c": "NM_000024.5:c.45_47delTAGinsNNNN",
"g": "NC_000005.9:g.148206439_148206441delTGGinsNNNN",
"n": "NM_000024.5:n.284_286delTAGinsNNNN",
},
{
"c": "NM_000024.5:c.45_47delTAGinsNNNN",
"g": "NC_000005.9:g.148206439_148206441delTGGinsNNNN",
"n": "NM_000024.5:n.284_286delTAGinsNNNN",
},
{
"c": "NM_000024.5:c.46dupA",
"g": "NC_000005.9:g.148206440dupG",
"n": "NM_000024.5:n.285dupA",
},
# IFNA16 │ NM_002173.2 │ 6 │ 576 │ NC_000009.11 │ -1 │ 21216371, 21217310 | 691=2X246=
# cseq = hdp.fetch_seq("NM_002173.2")
# gseq = reverse_complement(hdp.fetch_seq("NC_000009.11",21216371,21217310))
# cseq[685:695] = "AAATTTCAAA"
# gseq[685:695] = "AAATTTTCAA"
# ^^ @ n.692_693
# These variants are in and around the 2X substitution
{
"c": "NM_002173.2:c.*110A>N",
"g": "NC_000009.11:g.21216625T>N",
"n": "NM_002173.2:n.686A>N",
},
{
"c": "NM_002173.2:c.*111A>N",
"g": "NC_000009.11:g.21216624T>N",
"n": "NM_002173.2:n.687A>N",
},
{
"c": "NM_002173.2:c.*112A>N",
"g": "NC_000009.11:g.21216623T>N",
"n": "NM_002173.2:n.688A>N",
},
{
"c": "NM_002173.2:c.*113T>N",
"g": "NC_000009.11:g.21216622A>N",
"n": "NM_002173.2:n.689T>N",
},
{
"c": "NM_002173.2:c.*114T>N",
"g": "NC_000009.11:g.21216621A>N",
"n": "NM_002173.2:n.690T>N",
},
{
"c": "NM_002173.2:c.*115T>N",
"g": "NC_000009.11:g.21216620A>N",
"n": "NM_002173.2:n.691T>N",
},
{
"c": "NM_002173.2:c.*116C>N",
"g": "NC_000009.11:g.21216619A>N",
"n": "NM_002173.2:n.692C>N",
}, # ref repl
{
"c": "NM_002173.2:c.*117A>N",
"g": "NC_000009.11:g.21216618G>N",
"n": "NM_002173.2:n.693A>N",
}, # ref repl
{
"c": "NM_002173.2:c.*118A>N",
"g": "NC_000009.11:g.21216617T>N",
"n": "NM_002173.2:n.694A>N",
},
{
"c": "NM_002173.2:c.*119A>N",
"g": "NC_000009.11:g.21216616T>N",
"n": "NM_002173.2:n.695A>N",
},
# ins, del, delins, dup:
{
"c": "NM_002173.2:c.*115_*117insNN",
"g": "NC_000009.11:g.21216618_21216620insNN",
"n": "NM_002173.2:n.691_693insNN",
},
{
"c": "NM_002173.2:c.*114_*117delTTCA",
"g": "NC_000009.11:g.21216618_21216621delGAAA",
"n": "NM_002173.2:n.690_693delTTCA",
},
{
"c": "NM_002173.2:c.*115_*117delTCAinsNN",
"g": "NC_000009.11:g.21216618_21216620delGAAinsNN",
"n": "NM_002173.2:n.691_693delTCAinsNN",
},
{
"c": "NM_002173.2:c.*115_*117delTCAinsNN",
"g": "NC_000009.11:g.21216618_21216620delGAAinsNN",
"n": "NM_002173.2:n.691_693delTCAinsNN",
},
{
"c": "NM_002173.2:c.*115_*117dupTCA",
"g": "NC_000009.11:g.21216618_21216620dupGAA",
"n": "NM_002173.2:n.691_693dupTCA",
},
# genomic variation within an indel discrepancy
# NM_032790.3 c 108 >
# NM_032790.3 n 301 > CGGGGAGCCCCCGGGGGCC------CCGCCACCGCCGCCGT
# |||||||||||||||||||------||||||||||||||||
# NC_000012.11 g 122064755 > CGGGGAGCCCCCGGGGGCCCCGCCACCGCCACCGCCGCCGT
# **********
{
"c": "NM_032790.3:c.125_128delCCCC",
"g": "NC_000012.11:g.122064772_122064781delCCCCGCCACC",
"n": "NM_032790.3:n.318_321delCCCC",
},
]
@classmethod
def setUpClass(cls):
def _parse_rec(rec):
rec["pv"] = {x: cls.hp.parse_hgvs_variant(rec[x]) for x in "cgn"}
return rec
cls.hdp = hgvs.dataproviders.uta.connect(
mode=os.environ.get("HGVS_CACHE_MODE", "run"), cache=CACHE
)
cls.am = hgvs.assemblymapper.AssemblyMapper(
cls.hdp, replace_reference=True, assembly_name="GRCh37", alt_aln_method="splign"
)
cls.hp = hgvs.parser.Parser()
cls.tests = [_parse_rec(rec) for rec in cls.test_cases]
def test_replace_reference_sequence(self):
"""AssemblyMapper: Replace invalid reference sequence"""
for rec in self.tests:
for x in "cgn":
pv = rec["pv"][x]
if pv.posedit.edit.ref:
# replace ref with junk
pv.posedit.edit.ref = "NNNNNN"
self.am._replace_reference(pv)
self.assertEqual(rec[x], pv.format(conf={"max_ref_length": None}))
@pytest.mark.quick
class Test_AssemblyMapper(unittest.TestCase):
@classmethod
def setUpClass(cls):
cls.hdp = hgvs.dataproviders.uta.connect(
mode=os.environ.get("HGVS_CACHE_MODE", "run"), cache=CACHE
)
cls.hp = hgvs.parser.Parser()
cls.am = hgvs.assemblymapper.AssemblyMapper(
cls.hdp, assembly_name="GRCh37", alt_aln_method="splign"
)
def _test_mapping(self, hgvs_set):
"""given list of variant strings, test all valid combinations of
g<->n<->c<->p mappings
"""
parsed_variants = [(hv, self.hp.parse_hgvs_variant(hv)) for hv in hgvs_set]
hgvs = {v.type: hv for hv, v in parsed_variants}
pvs = {v.type: v for hv, v in parsed_variants}
if "g" in pvs and "c" in pvs:
self.assertEqual(hgvs["g"], str(self.am.c_to_g(pvs["c"])))
self.assertEqual(hgvs["c"], str(self.am.g_to_c(pvs["g"], pvs["c"].ac)))
if "g" in pvs and "n" in pvs:
self.assertEqual(hgvs["g"], str(self.am.n_to_g(pvs["n"])))
self.assertEqual(hgvs["n"], str(self.am.g_to_n(pvs["g"], pvs["n"].ac)))
if "c" in pvs and "n" in pvs:
self.assertEqual(hgvs["n"], str(self.am.c_to_n(pvs["c"])))
self.assertEqual(hgvs["c"], str(self.am.n_to_c(pvs["n"])))
if "c" in pvs and "p" in pvs:
self.assertEqual(hgvs["p"], str(self.am.c_to_p(pvs["c"])))
self.assertEqual(hgvs["p"], str(self.am.t_to_p(pvs["c"])))
def test_SNV(self):
"""AssemblyMapper: smoketest with SNVs"""
hgvs_set = [
"NC_000007.13:g.36561662C>T",
"NM_001637.3:c.1582G>A",
"NM_001637.3:n.1983G>A",
"NP_001628.1:p.(Gly528Arg)",
]
self._test_mapping(hgvs_set)
def test_intronic(self):
"""AssemblyMapper: smoketest with intronic SNVs"""
hgvs_set = [
"NC_000010.10:g.89711873A>C",
"NM_000314.4:c.493-2A>C",
"NM_000314.4:n.1524-2A>C",
"NP_000305.3:p.?",
]
self._test_mapping(hgvs_set)
def test_t_to_p(self):
assert "non-coding" == str(self.am.t_to_p(self.hp.parse("NR_027676.1:n.3980del")))
assert "NP_000050.2:p.(Lys2597=)" == str(
self.am.t_to_p(self.hp.parse("NM_000059.3:c.7791A>G"))
)
def test_issue_704_set_prevalidation_level(self):
# Doesn't set prevalidation_level
for prevalidation_level in PrevalidationLevel:
am = hgvs.assemblymapper.AssemblyMapper(
self.hdp, replace_reference=True, assembly_name="GRCh37", alt_aln_method="splign",
normalize=True, prevalidation_level=prevalidation_level.name,
)
vm = am._norm.vm
self.assertEqual(vm.prevalidation_level, prevalidation_level,
"AssemblyMapper Normalizer has 'prevalidation_level' set")
if __name__ == "__main__":
unittest.main()
# <LICENSE>
# Copyright 2018 HGVS Contributors (https://github.com/biocommons/hgvs)
#
# Licensed under the Apache License, Version 2.0 (the "License");
# you may not use this file except in compliance with the License.
# You may obtain a copy of the License at
#
# http://www.apache.org/licenses/LICENSE-2.0
#
# Unless required by applicable law or agreed to in writing, software
# distributed under the License is distributed on an "AS IS" BASIS,
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
# See the License for the specific language governing permissions and
# limitations under the License.
# </LICENSE>