Import LRG transcript mappings from EBI map files

mutalyzer/entrypoints/admin.py

@@ -113,6 +113,20 @@ def import_mapview(assembly_name_or_alias, mapview_file, encoding,
         raise UserError(unicode(e))
 
 
+def import_lrgmap(assembly_name_or_alias, lrgmap_file, encoding):
+    """
+    Import transcript mappings from an EBI LRG transcripts map file.
+    """
+    lrgmap_file = codecs.getreader(encoding)(lrgmap_file)
+
+    try:
+        assembly = Assembly.by_name_or_alias(assembly_name_or_alias)
+    except NoResultFound:
+        raise UserError('Not a valid assembly: %s' % assembly_name_or_alias)
+
+    mapping.import_from_lrgmap_file(assembly, lrgmap_file)
+
+
 def import_gene(assembly_name_or_alias, gene):
     """
     Import transcript mappings for a gene from the UCSC database.
@@ -313,6 +327,22 @@ def main():
         help='use only entries with this group label (example: '
         'GRCh37.p2-Primary Assembly)')
 
+    # Subparser 'assemblies import-lrgmap'.
+    p = s.add_parser(
+        'import-lrgmap',
+        help='import mappings from EBI LRG transcripts map file',
+        parents=[assembly_parser],
+        description=import_lrgmap.__doc__.split('\n\n')[0])
+    p.set_defaults(func=import_lrgmap)
+    p.add_argument(
+        'lrgmap_file', metavar='FILE', type=argparse.FileType('rb'),
+        help='EBI LRG transcript map file (example: '
+        'list_LRGs_transcripts_GRCh37.txt)')
+    p.add_argument(
+        '--encoding', metavar='ENCODING', type=_cli_string,
+        default=default_encoding,
+        help='input file encoding (default: %s)' % default_encoding)
+
     # Subparser 'assemblies import-gene'.
     p = s.add_parser(
         'import-gene', help='import mappings by gene from UCSC database',

mutalyzer/mapping.py

@@ -1053,3 +1053,74 @@ def import_from_mapview_file(assembly, mapview_file, group_label):
             session.add(mapping)
 
     session.commit()
+
+
+def import_from_lrgmap_file(assembly, lrgmap_file):
+    """
+    Import transcript mappings from an EBI LRG transcripts map file.
+
+    All positions are one-based, inclusive, and that is what we also use in
+    our database.
+    """
+    columns = ['transcript', 'gene', 'chromosome', 'strand', 'start', 'stop',
+               'exons', 'protein', 'cds_start', 'cds_stop']
+
+    chromosomes = assembly.chromosomes.all()
+
+    def read_mappings(lrgmap_file):
+        for line in lrgmap_file:
+            if line.startswith('#'):
+                continue
+            record = dict(zip(columns, line.rstrip('\r\n').split('\t')))
+
+            record['start'] = int(record['start'])
+            record['stop'] = int(record['stop'])
+            try:
+                record['cds_start'] = int(record['cds_start'])
+            except ValueError:
+                record['cds_start'] = None
+            try:
+                record['cds_stop'] = int(record['cds_stop'])
+            except ValueError:
+                record['cds_stop'] = None
+            record['exons'] = [[int(pos) for pos in exon.split('-')]
+                               for exon in record['exons'].split(',')]
+
+            try:
+                yield build_mapping(record)
+            except ValueError:
+                pass
+
+    def build_mapping(record):
+        # Only use records on chromosomes we know.
+        try:
+            chromosome = next(c for c in chromosomes if
+                              c.name == 'chr' + record['chromosome'])
+        except StopIteration:
+            raise ValueError()
+
+        accession, transcript = record['transcript'].split('t')
+        transcript = int(transcript)
+
+        orientation = 'reverse' if record['strand'] == '-1' else 'forward'
+
+        if record['cds_start']:
+            cds = record['cds_start'], record['cds_stop']
+        else:
+            cds = None
+
+        # TODO: Also take protein into account. For example, in LRG_32 (TP53)
+        # some transcripts occur twice (with different CDSs and different
+        # protein numbers).
+        # https://humgenprojects.lumc.nl/trac/mutalyzer/ticket/150
+        return TranscriptMapping.create_or_update(
+            chromosome, 'lrg', accession, record['gene'], orientation,
+            record['start'], record['stop'],
+            [start for start, _ in record['exons']],
+            [stop for _, stop in record['exons']],
+            'ebi', transcript=transcript, cds=cds, select_transcript=True)
+
+    for mapping in read_mappings(lrgmap_file):
+        session.add(mapping)
+
+    session.commit()

tests/data/hg19.lrgmap.subset.txt

+# Last modified: 10-02-2016@22:00:03
+# LRG_TRANSCRIPT	HGNC_SYMBOL	CHROMOSOME	STRAND	TRANSCRIPT_START	TRANSCRIPT_STOP	EXONS_COORDS	LRG_PROTEIN	CDS_START	CDS_STOP
+LRG_1t1	COL1A1	17	-1	48261457	48279000	48261457-48263009,48263139-48263381,48263678-48263868,48264001-48264283,48264376-48264483,48264845-48264898,48265237-48265344,48265457-48265510,48265891-48265998,48266103-48266156,48266264-48266371,48266529-48266636,48266738-48266899,48267040-48267093,48267220-48267273,48267362-48267469,48267688-48267741,48267904-48267957,48268178-48268285,48268744-48268851,48269149-48269247,48269341-48269385,48269836-48269889,48270001-48270054,48270158-48270211,48270355-48270408,48271304-48271402,48271491-48271544,48271710-48271808,48271934-48271987,48272082-48272189,48272408-48272461,48272593-48272691,48272795-48272839,48272928-48273026,48273284-48273337,48273516-48273560,48273675-48273728,48273845-48273889,48273978-48274031,48274371-48274424,48274541-48274594,48275093-48275146,48275310-48275363,48275522-48275566,48275794-48275865,48276587-48276688,48276779-48276814,48276917-48276951,48277114-48277308,48278772-48279000	LRG_1p1	48262863	48278874
+LRG_2t1	COL1A2	7	1	94023873	94060544	94023873-94024413,94027060-94027070,94027694-94027708,94028361-94028396,94029508-94029600,94030879-94030932,94033868-94033912,94034005-94034058,94034151-94034204,94034511-94034564,94034985-94035038,94035562-94035615,94037159-94037203,94037495-94037548,94037648-94037692,94038082-94038135,94038634-94038732,94038876-94038920,94039035-94039133,94039554-94039607,94039732-94039839,94040201-94040254,94040368-94040466,94041380-94041433,94041896-94041994,94042395-94042448,94043002-94043055,94043206-94043259,94043534-94043587,94044538-94044582,94045717-94045815,94047036-94047143,94047811-94047864,94048810-94048863,94049545-94049598,94049703-94049756,94049853-94049960,94050321-94050374,94051211-94051264,94052269-94052430,94053648-94053755,94054429-94054536,94054922-94054975,94055062-94055169,94055310-94055363,94055735-94055842,94056320-94056373,94056500-94056607,94056939-94057197,94057605-94057789,94058500-94058742,94059559-94060544	LRG_2p1	94024344	94059705
+LRG_3t1	COL3A1	2	1	189839099	189877472	189839099-189839294,189849486-189849688,189849923-189849973,189850391-189850504,189851785-189851865,189852807-189852860,189853316-189853369,189854122-189854175,189854822-189854875,189855033-189855086,189855730-189855783,189856213-189856257,189856395-189856448,189856910-189856954,189857613-189857666,189858087-189858185,189858764-189858808,189858960-189859058,189859267-189859320,189859450-189859557,189859772-189859825,189860418-189860516,189860851-189860904,189861124-189861222,189861891-189861944,189862062-189862115,189862426-189862479,189862992-189863045,189863400-189863444,189864011-189864109,189864196-189864303,189864568-189864621,189866123-189866176,189866262-189866315,189867024-189867077,189867681-189867788,189868137-189868190,189868460-189868513,189868708-189868869,189868983-189869090,189870076-189870183,189870932-189870985,189871071-189871178,189871663-189871716,189872226-189872333,189872611-189872664,189872761-189872868,189873650-189873947,189874904-189875091,189875374-189875616,189876354-189877472	LRG_3p1	189839216	189876500
+LRG_4t1	CRTAP	3	1	33155450	33189265	33155450-33156040,33161836-33161985,33165900-33166071,33171431-33171559,33174047-33174192,33175674-33175757,33183887-33189265	LRG_4p1	33155570	33183940
+LRG_5t1	P3H1	1	-1	43212006	43232755	43212006-43212523,43212943-43213083,43213394-43213469,43213871-43213988,43215857-43216007,43217945-43218040,43218208-43218335,43220540-43220661,43220836-43220888,43221219-43221308,43223454-43223593,43224523-43224654,43224872-43225061,43227994-43228146,43232178-43232755	LRG_5p1	43212368	43232642
+LRG_5t2	P3H1	1	-1	43212006	43232755	43212006-43212523,43212924-43213083,43213394-43213469,43213871-43213988,43215857-43216007,43217945-43218040,43218208-43218335,43220540-43220661,43220836-43220888,43221219-43221308,43223454-43223593,43224523-43224654,43224872-43225061,43227994-43228146,43232178-43232755	LRG_5p2	43212504	43232642
+LRG_5t3	P3H1	1	-1	43212006	43232755	43212006-43213083,43213394-43213469,43213871-43213988,43215857-43216007,43217945-43218040,43218208-43218335,43220540-43220661,43220836-43220888,43221219-43221308,43223454-43223593,43224523-43224654,43224872-43225061,43227994-43228146,43232178-43232755	LRG_5p3	43212583	43232642
+LRG_6t1	ATP1A2	1	1	160085548	160113381	160085548-160085663,160090696-160090800,160090982-160091041,160093003-160093206,160093733-160093846,160094086-160094220,160094926-160095043,160097342-160097610,160098442-160098640,160098770-160098879,160099056-160099190,160099892-160100081,160100212-160100387,160104274-160104410,160104935-160105085,160105224-160105392,160105629-160105783,160106037-160106160,160106360-160106505,160106691-160106821,160109430-160109531,160109683-160109774,160111084-160113381	LRG_6p1	160085652	160111112
+LRG_160t1	PIGA	X	-1	15337573	15353676	15337573-15339894,15342787-15342993,15343142-15343274,15344036-15344168,15349338-15350114,15353623-15353676	LRG_160p1	15339628	15350052
+LRG_161t1	PMS2	7	-1	6012870	6048737	6012870-6013173,6017219-6017388,6018227-6018327,6022455-6022622,6026390-6027251,6029431-6029586,6031604-6031688,6035165-6035264,6036957-6037054,6038739-6038906,6042084-6042267,6043321-6043423,6043603-6043689,6045523-6045662,6048628-6048737	LRG_161p1	6013030	6048650			
+LRG_162t1	PRKDC	8	-1	48685669	48872743	48685669-48686938,48689405-48689544,48690247-48690435,48691020-48691221,48691289-48691360,48691565-48691654,48694723-48694815,48694939-48695159,48696303-48696370,48697674-48697878,48701467-48701610,48701712-48701799,48706851-48707062,48710798-48710958,48711771-48711951,48713354-48713547,48715867-48716041,48719698-48719887,48730011-48730122,48731963-48732071,48733280-48733504,48734165-48734353,48736419-48736557,48739217-48739422,48740729-48740908,48743166-48743297,48744375-48744487,48746757-48746957,48748899-48749088,48749773-48749980,48751709-48751807,48752577-48752750,48761715-48761864,48761940-48762064,48765234-48765345,48766644-48766775,48767783-48767934,48769717-48769860,48771077-48771196,48771410-48771547,48772172-48772320,48773460-48773532,48774623-48774688,48774934-48775102,48775960-48776138,48777117-48777324,48790285-48790412,48792052-48792219,48793977-48794081,48794473-48794658,48798505-48798708,48800108-48800266,48801079-48801211,48801575-48801783,48802818-48803041,48805700-48805947,48809721-48809854,48811030-48811129,48812933-48813027,48815129-48815355,48817429-48817536,48824970-48825122,48826461-48826624,48827888-48827978,48830837-48830943,48839754-48839913,48840331-48840450,48841652-48841738,48842413-48842572,48843232-48843347,48845580-48845732,48846525-48846650,48847569-48847618,48848292-48848460,48848913-48849077,48852111-48852257,48855769-48855926,48856413-48856443,48856534-48856589,48866180-48866279,48866367-48866479,48866898-48867006,48868434-48868508,48869731-48869823,48869915-48869991,48872533-48872743	LRG_162p1	48686734	48872686
+LRG_163t1	RMRP	9	-1	35657748	35658015	35657748-35658015			
+LRG_164t1	STIM1	11	1	3876933	4114440	3876933-3877639,3988782-3988912,4045103-4045217,4076756-4076867,4080511-4080626,4091256-4091433,4095732-4095909,4103414-4103581,4104112-4104212,4104493-4104728,4107707-4107773,4112512-4114440	LRG_164p1	3877501	4113028
+LRG_165t1	STXBP2	19	1	7701991	7712759	7701991-7702072,7703612-7703661,7703905-7703986,7704617-7704693,7705617-7705695,7705786-7705889,7706591-7706739,7706920-7707004,7707089-7707219,7707315-7707422,7707652-7707709,7707869-7707934,7708051-7708131,7709500-7709638,7710083-7710192,7711135-7711230,7712048-7712133,7712240-7712397,7712611-7712759	LRG_165p1	7702036	7712696
+LRG_166t1	TAP1	6	-1	32812986	32821748	32812986-32813562,32814845-32814981,32815290-32815452,32815696-32815869,32816429-32816617,32816767-32816895,32818097-32818294,32818721-32818926,32819886-32820016,32820165-32820279,32820816-32821748	LRG_166p1	32813356	32821593
+LRG_167t1	TAP2	6	-1	32793187	32806547	32793187-32796811,32797177-32797313,32797707-32797866,32798044-32798217,32798395-32798583,32800110-32800238,32800404-32800601,32802931-32803136,32803420-32803550,32805314-32805428,32805518-32806014,32806430-32806547	LRG_167p1	32796632	32806010
+LRG_167t2	TAP2	6	-1	32789610	32806547	32789610-32790095,32797177-32797313,32797707-32797866,32798044-32798217,32798395-32798583,32800110-32800238,32800404-32800601,32802931-32803136,32803420-32803550,32805314-32805428,32805518-32806014,32806430-32806547	LRG_167p2	32790066	32806010
+LRG_168t1	THBD	20	-1	23026270	23030301	23026270-23030301	LRG_168p1	23028414	23030141
+LRG_341t2	UNC119	17	-1	26873725	26879646	26873725-26874867,26875017-26875119,26875610-26875723,26879356-26879646	LRG_341p2	26874642	26879575
+LRG_343t1	TERT	5	-1	1253282	1295162	1253282-1253946,1254483-1254620,1255402-1255526,1258713-1258774,1260589-1260715,1264519-1264707,1266579-1266650,1268635-1268748,1271234-1271319,1272300-1272395,1278756-1278911,1279406-1279585,1280273-1280453,1282544-1282739,1293428-1294781,1294886-1295162	LRG_343p1	1253843	1295104
+LRG_344t1	KRAS	12	-1	25357723	25403865	25357723-25362845,25368371-25368494,25378548-25378707,25380168-25380346,25398208-25398329,25403685-25403865	LRG_344p1	25368375	25398318
+LRG_344t2	KRAS	12	-1	25357723	25403865	25357723-25362845,25378548-25378707,25380168-25380346,25398208-25398329,25403685-25403865	LRG_344p2	25362729	25398318
+LRG_345t1	NOP10	15	-1	34633917	34635362	34633917-34634309,34635221-34635362	LRG_345p1	34634169	34635274
+LRG_346t1	NHP2	5	-1	177576464	177580961	177576464-177576839,177577889-177577994,177580492-177580561,177580659-177580961	LRG_346p1	177576714	177580818
+LRG_347t1	TERC	3	-1	169482398	169482848	169482398-169482848			
+LRG_348t1	CR2	1	1	207627645	207663240	207627645-207627821,207639871-207640257,207641869-207642060,207642145-207642247,207642495-207642577,207643040-207643447,207644085-207644261,207644342-207644432,207644768-207644844,207646117-207646524,207646890-207647066,207647146-207647230,207647586-207647668,207648169-207648561,207649579-207649764,207651230-207651415,207652602-207652625,207653323-207653398,207658809-207658917,207662487-207663240	LRG_348p1	207627764	207658899
+LRG_349t1	MASP1	3	-1	186964142	187009810	186964142-186965173,186968039-186968117,186969422-186969540,186970956-186971103,186974452-186974648,186978529-186978660,186980331-186980508,187003613-187003844,187009416-187009810	LRG_349p1	186965121	187009420
+LRG_349t2	MASP1	3	-1	186933873	187009810	186933873-186938049,186938823-186938922,186940915-186940982,186943112-186943297,186944195-186944308,186947548-186947685,186959269-186959343,186961272-186961409,186968039-186968117,186969422-186969540,186970956-186971103,186974452-186974648,186978529-186978660,186980331-186980508,187003613-187003844,187009416-187009810	LRG_349p2	186937859	187009420

tests/test_mapping.py

@@ -448,3 +448,73 @@ def test_import_mapview(hg19):
     assert new.orientation == 'forward'
     assert new.reference_type == 'refseq'
     assert new.source == 'ncbi'
+
+
+def test_import_lrgmap(hg19):
+    original_count = TranscriptMapping.query.count()
+
+    path = os.path.join(os.path.dirname(os.path.realpath(__file__)), 'data',
+                        'hg19.lrgmap.subset.txt')
+    lrgmap = codecs.open(path, encoding='utf-8')
+    lrgmap_count = sum(1 for line in lrgmap if not line.startswith('#'))
+    lrgmap.seek(0)
+
+    mapping.import_from_lrgmap_file(hg19, lrgmap)
+
+    # Two transcripts were already in, the rest is new:
+    # - LRG_1
+    # - LRG_348
+    assert TranscriptMapping.query.count() == original_count + lrgmap_count - 2
+
+    # No changes here.
+    unchanged = TranscriptMapping.query.filter_by(accession='LRG_1').one()
+    assert unchanged.start == 48261457
+    assert unchanged.stop == 48279000
+    assert unchanged.exon_starts == [
+        48261457, 48263139, 48263678, 48264001, 48264376, 48264845, 48265237,
+        48265457, 48265891, 48266103, 48266264, 48266529, 48266738, 48267040,
+        48267220, 48267362, 48267688, 48267904, 48268178, 48268744, 48269149,
+        48269341, 48269836, 48270001, 48270158, 48270355, 48271304, 48271491,
+        48271710, 48271934, 48272082, 48272408, 48272593, 48272795, 48272928,
+        48273284, 48273516, 48273675, 48273845, 48273978, 48274371, 48274541,
+        48275093, 48275310, 48275522, 48275794, 48276587, 48276779, 48276917,
+        48277114, 48278772]
+    assert unchanged.exon_stops == [
+        48263009, 48263381, 48263868, 48264283, 48264483, 48264898, 48265344,
+        48265510, 48265998, 48266156, 48266371, 48266636, 48266899, 48267093,
+        48267273, 48267469, 48267741, 48267957, 48268285, 48268851, 48269247,
+        48269385, 48269889, 48270054, 48270211, 48270408, 48271402, 48271544,
+        48271808, 48271987, 48272189, 48272461, 48272691, 48272839, 48273026,
+        48273337, 48273560, 48273728, 48273889, 48274031, 48274424, 48274594,
+        48275146, 48275363, 48275566, 48275865, 48276688, 48276814, 48276951,
+        48277308, 48279000]
+    assert unchanged.cds == (48262863, 48278874)
+
+    # We made some artificial changes to the lrgmap file here.
+    updated = TranscriptMapping.query.filter_by(accession='LRG_348').one()
+    assert updated.start == 207627645
+    assert updated.stop == 207663240
+    assert updated.exon_starts == [
+        207627645, 207639871, 207641869, 207642145, 207642495, 207643040,
+        207644085, 207644342, 207644768, 207646117, 207646890, 207647146,
+        207647586, 207648169, 207649579, 207651230, 207652602, 207653323,
+        207658809, 207662487]
+    assert updated.exon_stops == [
+        207627821, 207640257, 207642060, 207642247, 207642577, 207643447,
+        207644261, 207644432, 207644844, 207646524, 207647066, 207647230,
+        207647668, 207648561, 207649764, 207651415, 207652625, 207653398,
+        207658917, 207663240]
+    assert updated.cds == (207627764, 207658899)
+
+    # This is a new entry.
+    new = TranscriptMapping.query.filter_by(accession='LRG_163').one()
+    assert new.version is None
+    assert new.start == 35657748
+    assert new.stop == 35658015
+    assert new.exon_starts == [35657748]
+    assert new.exon_stops == [35658015]
+    assert new.cds is None
+    assert new.gene == 'RMRP'
+    assert new.orientation == 'reverse'
+    assert new.reference_type == 'lrg'
+    assert new.source == 'ebi'