"""
Tests for the mutalyzer.mapping module.
"""
from __future__ import unicode_literals
import codecs
import os
import pytest
from mutalyzer.db.models import TranscriptMapping
from mutalyzer import mapping
# Some example positional coding/chromosomal mappings we use in the tests.
LRG_1_T1_POSITIONS = [
('-150', 48279024),
('-126', 48279000),
('-1', 48278875),
('1', 48278874),
('103', 48278772),
('103+5', 48278767),
('104-5', 48277313),
('104', 48277308),
('870', 48273878),
('4248', 48263139),
('4249', 48263009),
('4395', 48262863),
('*1', 48262862),
('*1406', 48261457),
('*1407', 48261456),
('*1417', 48261446)]
LRG_348_T1_POSITIONS = [
('-150', 207627614),
('-119', 207627645),
('-1', 207627763),
('1', 207627764),
('58', 207627821),
('58+5', 207627826),
('59-5', 207639866),
('59', 207639871),
('3279', 207658899),
('*1', 207658900),
('*772', 207663240),
('*780', 207663248)]
pytestmark = pytest.mark.usefixtures('hg19_transcript_mappings')
@pytest.fixture
def converter(output, hg19):
return mapping.Converter(hg19, output)
def test_converter(converter):
"""
Simple test.
"""
genomic = converter.c2chrom('NM_003002.2:c.274G>T')
assert genomic == 'NC_000011.9:g.111959695G>T'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.274G>T' in coding
# Fix for r536: disable the -u and +d convention.
# assert 'NR_028383.1:c.1-u2173C>A' in coding
assert 'NR_028383.1:n.-2173C>A' in coding
def test_converter_non_coding(converter):
"""
Test with variant on non-coding transcript.
"""
genomic = converter.c2chrom('NR_028383.1:n.-2173C>A')
assert genomic == 'NC_000011.9:g.111959695G>T'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.274G>T' in coding
# Fix for r536: disable the -u and +d convention.
# assert 'NR_028383.1:c.1-u2173C>A' in coding
assert 'NR_028383.1:n.-2173C>A' in coding
def test_converter_compound(converter):
"""
Test with compound variant.
"""
genomic = converter.c2chrom('NM_003002.2:c.[274G>T;278A>G]')
assert genomic == 'NC_000011.9:g.[111959695G>T;111959699A>G]'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.[274G>T;278A>G]' in coding
assert 'NR_028383.1:n.[-2173C>A;-2177T>C]' in coding
def test_hla_cluster(converter):
"""
Convert to primary assembly.
Transcript NM_000500.5 is mapped to different chromosome locations,
but we like to just see the primary assembly mapping to chromosome 6.
See also bug #58.
"""
# Todo: This test is bogus now that we use a fixture that has just the
# mapping to chromosome 6. However, I think we only get this mapping
# from our current source (NCBI seq_gene.md) anyway, so I'm not sure
# where we got the other mappings from in the past (but haven't
# investigated really).
genomic = converter.c2chrom('NM_000500.5:c.92C>T')
assert genomic == 'NC_000006.11:g.32006291C>T'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_000500.5:c.92C>T' in coding
def test_converter_del_length_reverse(converter):
"""
Position converter on deletion (denoted by length) on transcripts
located on the reverse strand.
"""
coding = converter.chrom2c(
'NC_000022.10:g.51016285_51017117del123456789', 'list')
# Fix for r536: disable the -u and +d convention.
# assert 'NM_001145134.1:c.-138-u21_60del123456789' in coding
# assert 'NR_021492.1:c.1-u5170_1-u4338del123456789' in coding
assert 'NM_001145134.1:c.-159_60del123456789' in coding
assert 'NR_021492.1:n.-5170_-4338del123456789' in coding
def test_S_Venkata_Suresh_Kumar(converter):
"""
Test for correct mapping information on genes where CDS start or stop
is exactly on the border of an exon.
Bug reported February 24, 2012 by S Venkata Suresh Kumar.
"""
coding = converter.chrom2c(
'NC_000001.10:g.115259837_115259837delT', 'list')
assert 'NM_001007553.1:c.3863delA' not in coding
assert 'NM_001007553.1:c.*953delA' in coding
assert 'NM_001130523.1:c.*953delA' in coding
def test_S_Venkata_Suresh_Kumar_more(converter):
"""
Another test for correct mapping information on genes where CDS start
or stop is exactly on the border of an exon.
Bug reported March 21, 2012 by S Venkata Suresh Kumar.
"""
coding = converter.chrom2c(
'NC_000001.10:g.160012314_160012329del16', 'list')
assert 'NM_002241.4:c.-27250-7_-27242del16' not in coding
assert 'NM_002241.4:c.1-7_9del16' in coding
def test_range_order_forward_correct(converter):
"""
Just a normal position converter call, both directions. See Trac #95.
"""
genomic = converter.c2chrom('NM_003002.2:c.-1_274del')
assert genomic == 'NC_000011.9:g.111957631_111959695del'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.-1_274del' in coding
def test_range_order_forward_incorrect_c2chrom(output, converter):
"""
Incorrect order of a range on the forward strand. See Trac #95.
"""
genomic = converter.c2chrom('NM_003002.2:c.274_-1del')
assert genomic is None
erange = output.getMessagesWithErrorCode('ERANGE')
assert len(erange) == 1
def test_range_order_reverse_correct(converter):
"""
Just a normal position converter call on the reverse strand, both
directions. See Trac #95.
"""
genomic = converter.c2chrom('NM_001162505.1:c.-1_40del')
assert genomic == 'NC_000020.10:g.48770135_48770175del'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_001162505.1:c.-1_40del' in coding
def test_range_order_reverse_incorrect_c2chrom(output, converter):
"""
Incorrect order of a range on the reverse strand. See Trac #95.
"""
genomic = converter.c2chrom('NM_001162505.1:c.40_-1del')
assert genomic is None
erange = output.getMessagesWithErrorCode('ERANGE')
assert len(erange) == 1
def test_range_order_incorrect_chrom2c(output, converter):
"""
Incorrect order of a chromosomal range. See Trac #95.
"""
coding = converter.chrom2c('NC_000011.9:g.111959695_111957631del', 'list')
assert coding is None
erange = output.getMessagesWithErrorCode('ERANGE')
assert len(erange) == 1
def test_delins_large_ins_c2chrom(converter):
"""
Delins with multi-base insertion c. to chrom.
"""
genomic = converter.c2chrom('NM_003002.2:c.274delinsTAAA')
assert genomic == 'NC_000011.9:g.111959695delinsTAAA'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.274delinsTAAA' in coding
def test_delins_large_ins_explicit_c2chrom(converter):
"""
Delins with multi-base insertion and explicit deleted sequence c. to chrom.
"""
genomic = converter.c2chrom('NM_003002.2:c.274delGinsTAAA')
assert genomic == 'NC_000011.9:g.111959695delinsTAAA'
coding = converter.chrom2c(genomic, 'list')
assert 'NM_003002.2:c.274delinsTAAA' in coding
def test_delins_large_ins_chrom2c(converter):
"""
Delins with multi-base insertion chrom to c.
"""
coding = converter.chrom2c('NC_000011.9:g.111959695delinsTAAA', 'list')
assert 'NM_003002.2:c.274delinsTAAA' in coding
def test_delins_large_ins_explicit_chrom2c(converter):
"""
Delins with multi-base insertion and explicit deleted sequence chrom to c.
"""
coding = converter.chrom2c('NC_000011.9:g.111959695delGinsTAAA', 'list')
assert 'NM_003002.2:c.274delinsTAAA' in coding
def test_chrm_chrom2c(converter):
"""
Mitochondrial m. to c.
"""
coding = converter.chrom2c('NC_012920.1:m.12030del', 'list')
assert 'NC_012920.1(ND4_v001):c.1271del' in coding
def test_chrm_name_chrom2c(converter):
"""
Mitochondrial m. (by chromosome name) to c.
"""
variant = converter.correctChrVariant('chrM:m.12030del')
coding = converter.chrom2c(variant, 'list')
assert 'NC_012920.1(ND4_v001):c.1271del' in coding
def test_chrm_c2chrom(converter):
"""
Mitochondrial c. to m.
"""
genomic = converter.c2chrom('NC_012920.1(ND4_v001):c.1271del')
assert genomic == 'NC_012920.1:m.12030del'
def test_nm_without_selector_chrom2c(converter):
"""
NM reference without transcript selection c. to g.
"""
genomic = converter.c2chrom('NM_017780.2:c.109A>T')
assert genomic == 'NC_000008.10:g.61654100A>T'
def test_nm_with_selector_chrom2c(converter):
"""
NM reference with transcript selection c. to g.
"""
genomic = converter.c2chrom('NM_017780.2(CHD7_v001):c.109A>T')
assert genomic == 'NC_000008.10:g.61654100A>T'
def test_nm_c2chrom_no_selector(converter):
"""
To NM reference should never result in transcript selection.
"""
variant = converter.correctChrVariant('NC_000008.10:g.61654100A>T')
coding = converter.chrom2c(variant, 'list')
assert 'NM_017780.2:c.109A>T' in coding
def test_incorrect_selector_c2chrom(output, converter):
"""
Incorrect selector.
"""
converter.c2chrom('NM_017780.2(CHD8):c.109A>T')
erange = output.getMessagesWithErrorCode('EACCNOTINDB')
assert len(erange) == 1
def test_incorrect_selector_version_c2chrom(output, converter):
"""
Incorrect selector version.
"""
converter.c2chrom('NM_017780.2(CHD7_v002):c.109A>T')
erange = output.getMessagesWithErrorCode('EACCNOTINDB')
assert len(erange) == 1
def test_no_selector_version_c2chrom(converter):
"""
Selector but no selector version.
"""
genomic = converter.c2chrom('NM_017780.2(CHD7):c.109A>T')
assert genomic == 'NC_000008.10:g.61654100A>T'
def test_incorrect_selector_no_selector_version_c2chrom(output, converter):
"""
Incorrect selector, no selector version.
"""
converter.c2chrom('NM_017780.2(CHD8):c.109A>T')
erange = output.getMessagesWithErrorCode('EACCNOTINDB')
assert len(erange) == 1
def test_ins_seq_chrom2c(converter):
"""
Insertion of a sequence (chrom2c).
"""
coding = converter.chrom2c(
'NC_000011.9:g.111957482_111957483insGAT', 'list')
assert 'NM_003002.2:c.-150_-149insGAT' in coding
assert 'NM_012459.2:c.10_11insATC' in coding
def test_ins_seq_seq(converter):
"""
Insertion of two sequences (chrom2c).
"""
coding = converter.chrom2c(
'NC_000011.9:g.111957482_111957483ins[GAT;AAA]', 'list')
assert 'NM_003002.2:c.-150_-149ins[GAT;AAA]' in coding
assert 'NM_012459.2:c.10_11ins[TTT;ATC]' in coding
def test_ins_seq_c2chrom_reverse(converter):
"""
Insertion of a sequence on reverse strand (c2chrom).
"""
genomic = converter.c2chrom('NM_012459.2:c.10_11insATC')
assert genomic == 'NC_000011.9:g.111957482_111957483insGAT'
def test_ins_seq_seq_c2chrom_reverse(converter):
"""
Insertion of two sequences on reverse strand (c2chrom).
"""
genomic = converter.c2chrom('NM_012459.2:c.10_11ins[TTT;ATC]')
assert genomic == 'NC_000011.9:g.111957482_111957483ins[GAT;AAA]'
@pytest.mark.parametrize('coding,chromosomal', LRG_1_T1_POSITIONS)
def test_lrg_1t1_c2chrom(converter, coding, chromosomal):
"""
Conversion from LRG reference on reverse strand.
"""
chromosomal_descr = converter.c2chrom('LRG_1t1:c.%sdel' % coding)
assert chromosomal_descr == 'NC_000017.10:g.%ddel' % chromosomal
@pytest.mark.parametrize('coding,chromosomal', LRG_1_T1_POSITIONS)
def test_lrg_1t1_chrom2c(converter, coding, chromosomal):
"""
Conversion to LRG reference on reverse strand.
"""
coding_descr = converter.chrom2c(
'NC_000017.10:g.%ddel' % chromosomal, 'list')
assert 'LRG_1t1:c.%sdel' % coding in coding_descr
@pytest.mark.parametrize('coding,chromosomal', LRG_348_T1_POSITIONS)
def test_lrg_348t1_c2chrom(converter, coding, chromosomal):
"""
Conversion from LRG reference on forward strand.
"""
chromosomal_descr = converter.c2chrom('LRG_348t1:c.%sdel' % coding)
assert chromosomal_descr == 'NC_000001.10:g.%ddel' % chromosomal
@pytest.mark.parametrize('coding,chromosomal', LRG_348_T1_POSITIONS)
def test_lrg_348t1_chrom2c(converter, coding, chromosomal):
"""
Conversion to LRG reference on forward strand.
"""
coding_descr = converter.chrom2c(
'NC_000001.10:g.%ddel' % chromosomal, 'list')
assert 'LRG_348t1:c.%sdel' % coding in coding_descr
def test_import_mapview(hg19):
original_count = TranscriptMapping.query.count()
group_label = 'GRCh37.p13-Primary Assembly'
path = os.path.join(os.path.dirname(os.path.realpath(__file__)), 'data',
'hg19.chr11.111771755-112247252.seq_gene.sorted.md')
mapview = codecs.open(path, encoding='utf-8')
mapview_count = sum(1 for line in mapview
if line.split('\t')[12] == group_label
and line.split('\t')[11] == 'RNA')
mapview.seek(0)
mapping.import_from_mapview_file(hg19, mapview, group_label)
# Two transcripts were already in, the rest is new:
# - NR_028383.1
# - NM_012459.2
assert TranscriptMapping.query.count() == original_count + mapview_count - 2
# No changes here.
unchanged = TranscriptMapping.query.filter_by(accession='NM_012459').one()
assert unchanged.start == 111955524
assert unchanged.stop == 111957522
assert unchanged.exon_starts == [111955524, 111957364]
assert unchanged.exon_stops == [111956186, 111957522]
assert unchanged.cds == (111956019, 111957492)
# We made some artificial changes to the mapview file here.
updated = TranscriptMapping.query.filter_by(accession='NR_028383').one()
assert updated.start == 111955524
assert updated.stop == 111957525
assert updated.exon_starts == [111955524, 111956700, 111957364]
assert updated.exon_stops == [111956180, 111957034, 111957525]
# This is a new entry.
new = TranscriptMapping.query.filter_by(accession='NM_000317').one()
assert new.version == 2
assert new.start == 112097088
assert new.stop == 112104696
assert new.exon_starts == [112097088, 112099317, 112100931, 112101349,
112103886, 112104155]
assert new.exon_stops == [112097249, 112099396, 112100953, 112101405,
112103956, 112104696]
assert new.cds == (112097167, 112104278)
assert new.gene == 'PTS'
assert new.orientation == 'forward'
assert new.reference_type == 'refseq'
assert new.source == 'ncbi'