public void GetCdnaPositionOffset_Intron_ReqL_Reverse()
{
var regions = new ITranscriptRegion[]
{
new TranscriptRegion(TranscriptRegionType.Intron, 10, 108901173, 108918171, 422, 423)
};
var translation = new Mock <ITranslation>();
translation.SetupGet(x => x.CodingRegion).Returns(new CodingRegion(108813927, 108941437, 129, 1613, 1485));
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(108810721);
transcript.SetupGet(x => x.End).Returns(108918171);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(true);
transcript.SetupGet(x => x.TranscriptRegions).Returns(regions);
transcript.SetupGet(x => x.Translation).Returns(translation.Object);
var po = HgvsUtilities.GetCdnaPositionOffset(transcript.Object, 108909672, 0, true);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(8500, po.Offset);
Assert.Equal(422, po.Position);
Assert.Equal("294+8500", po.Value);
}
public void GetCdnaPositionOffset_Gap_Forward_ReturnNull()
{
var regions = new ITranscriptRegion[]
{
new TranscriptRegion(TranscriptRegionType.Gap, 1, 134901, 135802, 1760, 2661)
};
var translation = new Mock <ITranslation>();
translation.SetupGet(x => x.CodingRegion).Returns(new CodingRegion(138530, 139309, 71, 850, 780));
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(134901);
transcript.SetupGet(x => x.End).Returns(139379);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(false);
transcript.SetupGet(x => x.TranscriptRegions).Returns(regions);
transcript.SetupGet(x => x.Translation).Returns(translation.Object);
var po = HgvsUtilities.GetCdnaPositionOffset(transcript.Object, 135001, 0, false);
Assert.NotNull(po);
Assert.True(po.HasStopCodonNotation);
Assert.Equal(0, po.Offset);
Assert.Equal(1760, po.Position);
Assert.Equal("*910", po.Value);
}
public void IsAminoAcidDuplicate_True()
{
var observedResult = HgvsUtilities.IsAminoAcidDuplicate(85, "P",
"MEAAAGGRGCFQPHPGLQKTLEQFHLSSMSSLGGPAAFSARWAQEAYKKESAKEAGAAAVPAPVPAATEPPPVLHLPAIQPPPPVLPGPFFMPSDRSTERCETVLEGETISCFVVGGEKRLCLPQILNSVLRDFSLQQINAVCDELHIYCSRCTADQLEILKVMGILPFSAPSCGLITKTDAERLCNALLYGGAYPPPCKKELAASLALGLELSERSVRVYHECFGKCKGLLVPELYSSPSAACIQCLDCRLMYPPHKFVVHSHKALENRTCHWGFDSANWRAYILLSQDYTGKEEQARLGRCLDDVKEKFDYGNKYKRRVPRVSSEPPASIRPKTDDTSSQSPAPSEKDKPSSWLRTLAGSSNKSLGCVHPRQRLSAFRPWSPAVSASEKELSPHLPALIRDSFYSYKSFETAVAPNVALAPPAQQKVVSSPPCAAAVSRAPEPLATCTQPRKRKLTVDTPGAPETLAPVAAPEEDKDSEAEVEVESREEFTSSLSSLSSPSFTSSSSAKDLGSPGARALPSAVPDAAAPADAPSGLEAELEHLRQALEGGLDTKEAKEKFLHEVVKMRVKQEEKLSAALQAKRSLHQELEFLRVAKKEKLREATEAKRNLRKEIERLRAENEKKMKEANESRLRLKRELEQARQARVCDKGCEAGRLRAKYSAQIEDLQVKLQHAEADREQLRADLLREREAREHLEKVVKELQEQLWPRARPEAAGSEGAAELEP");
Assert.True(observedResult);
}
public void IsAminoAcidDuplicate_False()
{
var observedResult = HgvsUtilities.IsAminoAcidDuplicate(307, "*RX",
"MHYDGHVRFDLPPQGSVLARNVSTRSCPPRTSPAVDLEEEEEESSVDGKGDRKSTGLKLSKKKARRRHTDDPSKECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKAPAKPGDEGKVEQGMKDSKSLSLPILRPAGTGPPALERVDAQSRRESLDILAPGRRRKNMSEFLGEASIPGQEPPTPSSCSLPSGSSGSTNTGDSWKNRAASRFSGFFSSGPSTSAFGREVDKMEQLEGKLHTYSLFGLPRLPRGLRFDHDSWEEEYDEDEDEDNACLRLEDSWRELIDGHEKLTRRQCHQQEAVWELLHTEASYIRKLRVIINLFLCCLLNLQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALLQPGDFLKGFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSVLRKTEEPRAKEAVVAMIGSVERFIHHVNACMRQRQERQRLAAVVSRIDAYEVVESSSDEVDKLLKEFLHLDLTAPIPGASPEETRQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTIYNAQNQLQQLRAQEPPGSQQPLQSLEEEEDEQEEEEEEEEEEEEGEDSGTSAASSPTIMRKSSGSPDSQHCASDGSTETLAMVVVEPGDTLSSPEFDSGPFSSQSDETSLSTTASSATPTSELLPLGPVDGRSCSMDSAYGTLSPTSLQDFVAPGPMAELVPRAPESPRVPSPPPSPRLRRRTPVQLLSCPPHLLKSKSEASLLQLLAGAGTHGTPSAPSRSLSELCLAVPAPGIRTQGSPQEAGPSWDCRGAPSPGSGPGLVGCLAGEPAGSHRKRCGDLPSGASPRVQPEPPPGVSAQHRKLTLAQLYRIRTTLLLNSTLTASEV");
Assert.False(observedResult);
}
public void GetCdnaPositionOffset_Intron_LeqR_Reverse()
{
var regions = new ITranscriptRegion[]
{
new TranscriptRegion(TranscriptRegionType.Exon, 2, 134901, 135802, 1760, 2661),
new TranscriptRegion(TranscriptRegionType.Intron, 1, 135803, 137619, 1759, 1760),
new TranscriptRegion(TranscriptRegionType.Exon, 1, 137620, 139379, 1, 1759)
};
var translation = new Mock <ITranslation>();
translation.SetupGet(x => x.CodingRegion).Returns(new CodingRegion(138530, 139309, 71, 850, 780));
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(134901);
transcript.SetupGet(x => x.End).Returns(139379);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(true);
transcript.SetupGet(x => x.TranscriptRegions).Returns(regions);
transcript.SetupGet(x => x.Translation).Returns(translation.Object);
var po = HgvsUtilities.GetCdnaPositionOffset(transcript.Object, 136711, 1, true);
Assert.NotNull(po);
Assert.True(po.HasStopCodonNotation);
Assert.Equal(909, po.Offset);
Assert.Equal(1759, po.Position);
Assert.Equal("*909+909", po.Value);
}
public void GetChangesAfterFrameshift_FirstAminoAcidIsStop()
{
var observedResult = HgvsUtilities.GetChangesAfterFrameshift(4, "MABCDEFGHIIIKL", "MABCDEFGHIIIKL*");
Assert.Equal(15, observedResult.Start);
Assert.Equal('*', observedResult.RefAminoAcid);
Assert.Equal('*', observedResult.AltAminoAcid);
}
public void GetChangesAfterFrameshift_AfterFrameshift()
{
var observedResult = HgvsUtilities.GetChangesAfterFrameshift(4, "MABCDEFGHIIIKL", "MABCEFGH*");
Assert.Equal(5, observedResult.Start);
Assert.Equal('D', observedResult.RefAminoAcid);
Assert.Equal('E', observedResult.AltAminoAcid);
}
public void IsDuplicateWithinInterval_outside_interval()
{
var simpleVar = GenSimpleInsertionMock();
// forward strand
Assert.False(HgvsUtilities.IsDuplicateWithinInterval(_refSequence, simpleVar.Object, new Interval(12344, 12370), false));
// reverse strand
Assert.False(HgvsUtilities.IsDuplicateWithinInterval(_refSequence, simpleVar.Object, new Interval(12340, 12347), true));
}
public void GetNumAminoAcidsUntilStopCodon_FoundExtraAminoAcids()
{
const int expectedResult = 38;
var observedResult =
HgvsUtilities.GetNumAminoAcidsUntilStopCodon(
"MLAEPFNWHVEYAHSGDVLGPSGLPASPGAPGTCLHNPAGSNWGPG*EVLMAGTVPAVPG*SGEGSQF*LPWSCSDSPQAGSRAHGQGPGIPLLPQGHGTQSLCRAQGSVPAAEPVPPTEDGRGLSGPEQGHRGTAPARRPPGGWQDLLLLSATLRL*RHCPQHQQ*LPARPGRLAAGCP*ETLWP*PLLSPAAGHRTRDLFPGGGDVPGGPLLRQAGCGADPAFPRPEPQGFGRPLEPAPCGAGGDHHERDRGC*RPHQLL*GVRCHSRRPPEPSDGGPHPRGHGAAPQCQQCGGCAAAQASGLPGAAGPAEGQCRRGPVPVLQ*AGAQRAAEARQLPQPDADLRSRPSAH*QPSLGGRAFHPDVWQSLGRESGLRSDLVQEPGLLCAERKALGRGAEPVPAPAARLPHRPWRPGQPCRAGQQEPVQALPALQLEGNGGTTWAPPFRQPSVRLLRLQPCAGAGRPLRPLIPYLPWPEEFLHHHRELAGLLELLDPSAGEPGP*GPTPLPWRS*EWPSVGL*VQ*RPVVLFPAAAGAAGARARAGPNAQ*LPGPQGQVPREPAGLRLVRGADL*AG**HRGHRCASRAALWPVPPGTVGGLEPRGPVPAAGHGALWLPLGPHAPVAG*RALRPTLRPGVQLPGPAGPPAAARPDPLLQHPPHACAPAAAALRRGGPGRPDLCQGDLSPGGQQQLRPGAAGHGCRRAHSLPLPTVTHWPGWRAAGRADHEPLPATPPHEP*PASHQPRQEGGSPGHGQDEA*DHHAGEPGGP*AQEVAHLGCPAALRPAGVVHGLRRLPGMRAPVPLARFAPVLSFARVFPPFSAPPPAQRALALQNLLSHSQAPERAGQALSRCL*PAALCIGG*MQKQGRNGVCS*EASNSGQERSLKKRPPAVTHSYQPAQHGMAPKLRRSQEET*RGGLRLIREGFLGEVILELAPGEHSEHDW*TEGCRGAQGSTLPRAKQGHWGLS*DPEGVKPLLPQLPLLLEPLHI*PLALLFTASTCSRLPSLSPPSWLCSRNSRLLPVSLLFFRLHL*RMRADNRNTVAKTRLWKGFQKSFFFFN*KKYLQR*ALAMLPRLVSNSWAQAILPSQPPRVLGLQV*ATAPSPRNLSAVWSSISHLMTCSAWGGGVSFPQLPQGGPLPSAAPLSC*PSSRKHTGCR*SGHSRDPQFKRVISISGDSRMGVSALNSPSCFTRKDPVKSPTEVTAH*RGERWSIE*HWAIQAALLPPDRS*ASLAGGLPTAFSGARLAGDGAAARPSLPAPW*PRGFLSAGLSCYLSLHHELSA*DWGSKRVSSQ*A*VGDCDLEKPWASNTCFSEAPKEGSDILFKNTTKQNSQDMCSFVCSVSHNLRLGDGTLG*GRFFCLASPHLPLALWIRQI*TF*RILREGFLG*GSMAKSVSLWTVYTSRRWI*RNPGFHFQCQSETCSQAGALVHTTYSGHQQQPRPDRASLFFFFETESLSPRLEPSGEILAHYNLHLPGSGNSRA*ASRVAATTGAGQHACLIFVF**RQGFTMLPRLVSNS*AQAVYPPQPPKVLGLQA*ATAPSQNICFYTQRAPLVRTEPRCPEPGSRPPGAQHLSFYT*WAGSGEDRESWWKFHSWPRGGALAPHCRLLTAPIPAAPVPDFISLLSPRVPGPSTLPSVLQEPTPLQLQHQGERGLHMPKYPCRMKGRPALDVPFLNNSHCRRV*DVLF*LSPASDAPPICAEWVWECG*GSKCQRSTFQNQVPSANHVGKVQTWRCPCASAPTHPFSFSCVRKEKFSEPSRLVAFKLQTMICSKKRAFHHKSVHLFTTVFQAGFIKKFLTLE",
"MLAEPFNWHPGMWNMLIVAMCLALLGCLQAQELQGHVSIILLGATGDLAKKYLWQGLFQLYLDEAGRGHSFSFHGAALTAPKQGQELMAKALESLSCPKDMAPSHCAEHKDQFLQLSQYRQLKTAEDYQALNKDIEAQLQHAGLREAGRIFYFSVPPFAYEDIARNINSSCRPGPGAWLRVVLEKPFGHDHFSAQQLATELGTFFQEEEMYRVDHYLGKQAVAQILPFRDQNRKALDGLWNRHHVERVEIIMKETVDAEGRTSFYEEYGVIRDVLQNHLTEVLTLVAMELPHNVSSAEAVLRHKLQVFQALRGLQRGSAVVGQYQSYSEQVRRELQKPDSFHSLTPTFAAVLVHIDNLRWEGVPFILMSGKALDERVGYARILFKNQACCVQSEKHWAAAQSQCLPRQLVFHIGHGDLGSPAVLVSRNLFRPSLPSSWKEMEGPPGLRLFGSPLSDYYAYSPVRERDAHSVLLSHIFHGRKNFFITTENLLASWNFWTPLLESLAHKAPRLYPGGAENGRLLDFEFSSGRLFFSQQQPEQLVPGPGPAPMPSDFQVLRAKYRESPLVSAWSEELISKLANDIEATAVRAVRRFGQFHLALSGGSSPVALFQQLATAHYGFPWAHTHLWLVDERCVPLSDPESNFQGLQAHLLQHVRIPYYNIHPMPVHLQQRLCAEEDQGAQIYAREISALVANSSFDLVLLGMGADGHTASLFPQSPTGLDGEQLVVLTTSPSQPHRRMSLSLPLINRAKKVAVLVMGRMKREITTLVSRVGHEPKKWPISGVLPHSGQLVWYMDYDAFLG",
9, true);
Assert.Equal(expectedResult, observedResult);
}
public void GetNumAminoAcidsUntilStopCodon_FirstAminoAcidIsStop()
{
const int expectedResult = -1;
var observedResult =
HgvsUtilities.GetNumAminoAcidsUntilStopCodon(
"RHRNRNTQTETNTETQRHRNTQKHRNKHRDTETHRNTETNTETQKHTETQKQTQRHRNTQKHTDRNKHRNTETQKYRNTQKHRNKHRDTETQKHSDAETQQHKHRNTETHRNRNTETNTETQTHRHRETQKHTETLKHSGRCPGCRGSIA",
"RHRNRNTQTETNTETQRHRNTQKHRNKHRDTETHRNTQKHRNKHRDTETHRNTETNTETQKHTETHRQKQTQKHRDTEIQKHTETQKQTQRHRDTETQRRRNTATQTQKHRNTQKQKHRNKHRDTDTQTQRNTETHRNTETQWAVSRLQRLHRC",
37, true);
Assert.Equal(expectedResult, observedResult);
}
public void GetCdnaPositionOffset_Intron_RltL_Forward()
{
var transcript = HgvsCodingNomenclatureTests.GetForwardTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 1262210, 1);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(-6, po.Offset);
Assert.Equal(337, po.Position);
Assert.Equal("-75-6", po.Value);
}
public void GetCdnaPositionOffset_Exon_Reverse()
{
var transcript = HgvsCodingNomenclatureTests.GetReverseTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 137721, 2, true);
Assert.NotNull(po);
Assert.True(po.HasStopCodonNotation);
Assert.Equal(0, po.Offset);
Assert.Equal(1659, po.Position);
Assert.Equal("*809", po.Value);
}
public void GetCdnaPositionOffset_Exon_Forward()
{
var transcript = HgvsCodingNomenclatureTests.GetForwardTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 1262627, 4, true);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(0, po.Offset);
Assert.Equal(540, po.Position);
Assert.Equal("129", po.Value);
}
public void GetCdnaPositionOffset_Intron_LeqR_Forward()
{
var transcript = HgvsCodingNomenclatureTests.GetForwardTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 1261349, 1, true);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(867, po.Offset);
Assert.Equal(336, po.Position);
Assert.Equal("-76+867", po.Value);
}
public void GetCdnaPositionOffset_Intron_RltL_Reverse()
{
var transcript = HgvsCodingNomenclatureTests.GetReverseTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 137619, 1, true);
Assert.NotNull(po);
Assert.True(po.HasStopCodonNotation);
Assert.Equal(2, po.Offset);
Assert.Equal(1759, po.Position);
Assert.Equal("*909+2", po.Value);
}
public void GetCdnaPositionOffset_Gap_RightSide_Forward()
{
var transcript = GetForwardGapTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 1102, 1, true);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(0, po.Offset);
Assert.Equal(101, po.Position);
Assert.Equal("51", po.Value);
}
public void GetCdnaPositionOffset_Gap_RightSide_Reverse()
{
var transcript = GetReverseGapTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 1103, 1, false);
Assert.NotNull(po);
Assert.False(po.HasStopCodonNotation);
Assert.Equal(0, po.Offset);
Assert.Equal(200, po.Position);
Assert.Equal("150", po.Value);
}
public void GetCdnaPositionOffset_Intron_LltR_Reverse()
{
var transcript = HgvsCodingNomenclatureTests.GetReverseTranscript();
var po = HgvsUtilities.GetCdnaPositionOffset(transcript, 136000, 1, true);
Assert.NotNull(po);
Assert.True(po.HasStopCodonNotation);
Assert.Equal(-198, po.Offset);
Assert.Equal(1760, po.Position);
Assert.Equal("*910-198", po.Value);
}
private static (string Hgvs, bool IsTranscriptSuffix) GetBreakEndHgvs(ITranscript transcript, int regionIndex,
int position, bool isGenomicSuffix)
{
var positionOffset = HgvsUtilities.GetCdnaPositionOffset(transcript, position, regionIndex);
var isTranscriptSuffix = isGenomicSuffix != transcript.Gene.OnReverseStrand;
var codingRegionLength = transcript.Translation.CodingRegion.CdnaEnd - transcript.Translation.CodingRegion.CdnaStart + 1;
var hgvsPosString = isTranscriptSuffix ? positionOffset.Value + "_" + codingRegionLength : 1 + "_" + positionOffset.Value;
var hgvs = transcript.Gene.Symbol + "{" + transcript.Id.WithVersion + "}" + ":c." + hgvsPosString;
return(hgvs, isTranscriptSuffix);
}
public void IsDuplicateWithinInterval_insertion_is_dup()
{
var simpleVar = GenSimpleInsertionMock();
// forward strand
Assert.True(HgvsUtilities.IsDuplicateWithinInterval(new SimpleSequence("ACCTGGGGC", 12340),
simpleVar.Object, new Interval(12300, 12400), false));
// reverse strand
Assert.True(HgvsUtilities.IsDuplicateWithinInterval(new SimpleSequence("ACTTCCTGC", 12340),
simpleVar.Object, new Interval(12300, 12400), true));
}
public void Rotate3Prime_Identity_Insertion()
{
const int expectedStart = 46;
const string expectedRefAminoAcids = "";
const string expectedAltAminoAcids = "A";
var observedResult = HgvsUtilities.Rotate3Prime("", "A", 44,
"MAAQVAPAAASSLGNPPPPPPSELKKAEQQQREEAGGEAAAAAAAERGEMKAAAGQESEGPAVGPPQPLGKELQDGAESNGGGGGGGAGSGGGPGAEPDLKNSNGNAGPRPALNNNLTEPPGGGGGGSSDGVGAPPHSAAAALPPPAYGFGQPYGRSPSAVAAAAAAVFHQQHGGQQSPGLAALQSGGGGGLEPYAGPQQNSHDHGFPNHQYNSYYPNRSAYPPPAPAYALSSPRGGTPGSGAAAAAGSKPPPSSSASASSSSSSFAQQRFGAMGGGGPSAAGGGTPQPTATPTLNQLLTSPSSARGYQGYPGGDYSGGPQDGGAGKGPADMASQCWGAAAAAAAAAAASGGAQQRSHHAPMSPGSSGGGGQPLARTPQPSSPMDQMGKMRPQPYGGTNPYSQQQGPPSGPQQGHGYPGQPYGSQTPQRYPMTMQGRAQSAMGGLSYTQQIPPYGQQGPSGYGQQGQTPYYNQQSPHPQQQQPPYSQQPPSQTPHAQPSYQQQPQSQPPQLQSSQPPYSQQPSQPPHQQSPAPYPSQQSTTQQHPQSQPPYSQPQAQSPYQQQQPQQPAPSTLSQQAAYPQPQSQQSQQTAYSQQRFPPPQELSQDSFGSQASSAPSMTSSKGGQEDMNLSLQSRPSSLPDLSGSIDDLPMGTEGALSPGVSTSGISSSQGEQSNPAQSPFSPHTSPHLPGIRGPSPSPVGSPASVAQSRSGPLSPAAVPGNQMPPRPPSGQSDSIMHPSMNQSSIAQDRGYMQRNPQMPQYSSPQPGSALSPRQPSGGQIHTGMGSYQQNSMGSYGPQGGQYGPQGGYPRQPNYNALPNANYPSAGMAGGINPMGAGGQMHGQPGIPPYGTLPPGRMSHASMGNRPYGPNMANMPPQVGSGMCPPPGGMNRKTQETAVAMHVAANSIQNRPPGYPNMNQGGMMGTGPPYGQGINSMAGMINPQGPPYSMGGTMANNSAGMAASPEMMGLGDVKLTPATKMNNKADGTPKTESKSKKSSSSTTTNEKITKLYELGGEPERKMWVDRYLAFTEEKAMGMTNLPAVGRKPLDLYRLYVSVKEIGGLTQVNKNKKWRELATNLNVGTSSSAASSLKKQYIQCLYAFECKIERGEDPPPDIFAAADSKKSQPKIQPPSPAGSGSMQGPQTPQSTSSSMAEGGDLKPPTPASTPHSQIPPLPGMSRSNSVGIQDAFNDGSDSTFQKRNSMTPNPGYQPSMNTSDMMGRMSYEPNKDPYGSMRKAPGSDPFMSSGQGPNGGMGDPYSRAAGPGLGNVAMGPRQHYPYGGPYDRVRTEPGIGPEGNMSTGAPQPNLMPSNPDSGMYSPSRYPPQQQQQQQQRHDSYGNQFSTQGTPSGSPFPSQQTTMYQQQQQNYKRPMDGTYGPPAKRHEGEMYSVPYSTGQGQPQQQQLPPAQPQPASQQQAAQPSPQQDVYNQYGNAYPATATAATERRPAGGPQNQFPFQFGRDRVSAPPGTNAQQNMPPQMMGGPIQASAEVAQQGTMWQGRNDMTYNYANRQSTGSAPQGPAYHGVNRTDEMLHTDQRANHEGSWPSHGTRQPPYGPSAPVPPMTRPPPSNYQPPPSMQNHIPQVSSPAPLPRPMENRTSPSKSPFLHSGMKMQKAGPPVPASHIAPAPVQPPMIRRDITFPPGSVEATQPVLKQRRRLTMKDIGTPEAWRVMMSLKSGLLAESTWALDTINILLYDDNSIMTFNLSQLPGLLELLVEYFRRCLIEIFGILKEYEVGDPGQRTLLDPGRFSKVSSPAPMEGGEEEEELLGPKLEEEEEEEVVENDEEIAFSGKDKPASENSEEKLISKFDKLPVKIVQKNDPFVVDCSDKLGRVQEFDSGLLHWRIGGGDTTEHIQTHFESKTELLPSRPHAPCPPAPRKHVTTAEGTPGTTDQEGPPPDGPPEKRITATMDDMLSTRSSTLTEDGAKSSEAIKESSKFPFGISPAQSHRNIKILEDEPHSKDETPLCTLLDWQDSLAKRCVCVSNTIRSLSFVPGNDFEMSKHPGLLLILGKLILLHHKHPERKQAPLTYEKEEEQDQGVSCNKVEWWWDCLEMLRENTLVTLANISGQLDLSPYPESICLPVLDGLLHWAVCPSAEAQDPFSTLGPNAVLSPQRLVLETLSKLSIQDNNVDLILATPPFSRLEKLYSTMVRFLSDRKNPVCREMAVVLLANLAQGDSLAARAIAVQKGSIGNLLGFLEDSLAATQFQQSQASLLHMQNPPFEPTSVDMMRRAARALLALAKVDENHSEFTLYESRLLDISVSPLMNSLVSQVICDVLFLIGQS");
Assert.Equal(expectedStart, observedResult.Start);
Assert.Equal(expectedRefAminoAcids, observedResult.RefAminoAcids);
Assert.Equal(expectedAltAminoAcids, observedResult.AltAminoAcids);
}
public void Rotate3Prime_Identity_WithNullAminoAcids()
{
const int expectedStart = 55;
const string expectedRefAminoAcids = "Q";
const string expectedAltAminoAcids = "*";
var observedResult = HgvsUtilities.Rotate3Prime(expectedRefAminoAcids, expectedAltAminoAcids, expectedStart,
"MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPLASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDDLFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS");
Assert.Equal(expectedStart, observedResult.Start);
Assert.Equal(expectedRefAminoAcids, observedResult.RefAminoAcids);
Assert.Equal(expectedAltAminoAcids, observedResult.AltAminoAcids);
}
public void ShiftAndRotateAlleles_Rotated()
{
int observedStart = 98;
string observedRefAminoAcids = "YYAKEV";
string observedAltAminoAcids = "Y";
HgvsUtilities.ShiftAndRotateAlleles(ref observedStart, ref observedRefAminoAcids, ref observedAltAminoAcids,
"MHYCVLSAFLILHLVTVALSLSTCSTLDMDQFMRKRIEAIRGQILSKLKLTSPPEDYPEPEEVPPEVISIYNSTRDLLQEKASRRAAACERERSDEEYYAKEVYKIDMPPFFPSENAIPPTFYRPYFRIVRFDVSAMEKNASNLVKAEFRVFRLQNPKARVPEQRIELYQILKSKDLTSPTQRYIDSKVVKTRAEGEWLSFDVTDAVHEWLHHKDRNLGFKISLHCPCCTFVPSNNYIIPNKSEELEARFAGIDGTSTYTSGDQKTIKSTRKKNSGKTPHLLLMLLPSYRLESQQTNRRKKRALDAAYCFRNVQDNCCLRPLYIDFKRDLGWKWIHEPKGYNANFCAGACPYLWSSDTQHSRVLSLYNTINPEASASPCCVSQDLEPLTILYYIGKTPKIEQLSNMIVKSCKCS");
Assert.Equal(100, observedStart);
Assert.Equal("AKEVY", observedRefAminoAcids);
Assert.Equal("", observedAltAminoAcids);
}
public void GetAltPeptideSequence_Genomic()
{
var refSequence = GetGenomicRefSequence();
var transcript = GetGenomicTranscript();
const int cdsBegin = 112;
const int cdsEnd = 121;
const string transcriptAltAllele = "";
const string expectedResult = "RHRNRNTQTETNTETQRHRNTQKHRNKHRDTETHRNTETNTETQKHTETQKQTQRHRNTQKHTDRNKHRNTETQKYRNTQKHRNKHRDTETQKHSDAETQQHKHRNTETHRNRNTETNTETQTHRHRETQKHTETLKHSGRCPGCRGSIA";
var observedResult =
HgvsUtilities.GetAltPeptideSequence(refSequence, cdsBegin, cdsEnd, transcriptAltAllele, transcript,
false);
Assert.Equal(expectedResult, observedResult);
}
AltAminoAcids, string RefCodons, string AltCodons, string TranscriptAltAllele, string TranscriptRefAllele) AnnotateTranscript(ITranscript transcript, ISimpleVariant variant, AminoAcids aminoAcids, ISequence refSequence)
{
bool onReverseStrand = transcript.Gene.OnReverseStrand;
var start = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.Start);
var end = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.End);
var position = GetMappedPosition(transcript.TranscriptRegions, start.Region, start.Index, end.Region,
end.Index, variant, onReverseStrand, transcript.Translation?.CodingRegion, transcript.StartExonPhase,
variant.Type == VariantType.insertion);
var codingSequence = GetCodingSequence(transcript, refSequence);
var cdnaSequence = GetCdnaSequence(transcript, refSequence);
string transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, onReverseStrand);
var codons = Codons.GetCodons(transcriptAltAllele, position.CdsStart, position.CdsEnd, position.ProteinStart, position.ProteinEnd, codingSequence);
var aa = aminoAcids.Translate(codons.Reference, codons.Alternate);
(aa, position.ProteinStart, position.ProteinEnd) = TryTrimAminoAcidsAndUpdateProteinPositions(aa, position.ProteinStart, position.ProteinEnd);
(position.CoveredCdnaStart, position.CoveredCdnaEnd) = transcript.TranscriptRegions.GetCoveredCdnaPositions(position.CdnaStart, start.Index, position.CdnaEnd, end.Index, onReverseStrand);
(position.CoveredCdsStart, position.CoveredCdsEnd, position.CoveredProteinStart, position.CoveredProteinEnd) = MappedPositionUtilities.GetCoveredCdsAndProteinPositions(position.CoveredCdnaStart, position.CoveredCdnaEnd, transcript.StartExonPhase, transcript.Translation?.CodingRegion);
var transcriptRefAllele = GetTranscriptRefAllele(position, cdnaSequence, variant, onReverseStrand);
SequenceChange coveredAa;
// only generate the covered version of ref & alt alleles when CDS start/end is -1
if (position.CdsStart == -1 || position.CdsEnd == -1)
{
coveredAa = GetCoveredAa(aminoAcids, transcriptAltAllele, position.CoveredCdsStart, position.CoveredCdsEnd, position.CoveredProteinStart, position.CoveredProteinEnd, codingSequence);
(coveredAa, position.CoveredProteinStart, position.CoveredProteinEnd) = TryTrimAminoAcidsAndUpdateProteinPositions(coveredAa, position.CoveredProteinStart, position.CoveredProteinEnd);
}
else
{
coveredAa = aa;
position.CoveredProteinStart = position.ProteinStart;
position.CoveredProteinEnd = position.ProteinEnd;
}
var positionalEffect = GetPositionalEffect(transcript, variant, position, aa.Reference, aa.Alternate,
position.CoveredCdnaStart, position.CoveredCdnaEnd, position.CoveredCdsStart, position.CoveredCdsEnd);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, aa.Reference, aa.Alternate,
codons.Reference, codons.Alternate, position.ProteinStart, coveredAa.Reference, coveredAa.Alternate);
return(variantEffect, position, aa.Reference, aa.Alternate, codons.Reference, codons.Alternate, transcriptAltAllele, transcriptRefAllele);
}
private static (string Begin, string End) AdjustFirst(BreakPointTranscript first)
{
var codingRegion = first.Transcript.Translation.CodingRegion;
int position = first.GenomicPosition;
int codingRegionLength = codingRegion.CdnaEnd - codingRegion.CdnaStart + 1;
if (position < codingRegion.Start)
{
return("?", (position - codingRegion.Start).ToString());
}
if (position > codingRegion.End)
{
return("?", (position - codingRegion.End + codingRegionLength).ToString());
}
return("1", HgvsUtilities.GetCdnaPositionOffset(first.Transcript, position, first.RegionIndex).Value);
}
private static (string Begin, string End) AdjustSecond(BreakPointTranscript second)
{
var codingRegion = second.Transcript.Translation.CodingRegion;
int position = second.GenomicPosition;
int codingRegionLength = codingRegion.CdnaEnd - codingRegion.CdnaStart + 1;
if (position < codingRegion.Start)
{
return((position - codingRegion.Start).ToString(), "?");
}
if (position > codingRegion.End)
{
return((position - codingRegion.End + codingRegionLength).ToString(), "?");
}
return(HgvsUtilities.GetCdnaPositionOffset(second.Transcript, position, second.RegionIndex).Value, codingRegionLength.ToString());
}
public static IAnnotatedTranscript GetAnnotatedTranscript(ITranscript transcript, IVariant variant, ISequence refSequence,
AminoAcids aminoAcidsProvider)
{
var mappedPositions = MappedPositionsUtils.ComputeMappedPositions(variant.Start, variant.End, transcript);
var transcriptRefAllele = HgvsUtilities.GetTranscriptAllele(variant.RefAllele, transcript.Gene.OnReverseStrand);
var transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, transcript.Gene.OnReverseStrand);
var codonsAndAminoAcids = GetCodonsAndAminoAcids(transcript, refSequence, transcriptRefAllele, transcriptAltAllele, variant, mappedPositions, aminoAcidsProvider);
var referenceCodons = codonsAndAminoAcids.Item1;
var alternateCodons = codonsAndAminoAcids.Item2;
var referenceAminoAcids = codonsAndAminoAcids.Item3;
var alternateAminoAcids = codonsAndAminoAcids.Item4;
var insertionInStartCodonAndNoimpact = variant.Type == VariantType.insertion &&
mappedPositions.ProteinInterval.Start <= 1 &&
alternateAminoAcids.EndsWith(referenceAminoAcids);
var variantEffect = GetVariantEffect(transcript, variant, mappedPositions, referenceAminoAcids,
alternateAminoAcids, referenceCodons, alternateCodons, insertionInStartCodonAndNoimpact);
var consequences = GetConsequences(transcript, variant, variantEffect);
var proteinBegin = mappedPositions.ProteinInterval.Start == null
? -1
: mappedPositions.ProteinInterval.Start.Value;
var proteinEnd = mappedPositions.ProteinInterval.End == null
? -1
: mappedPositions.ProteinInterval.End.Value;
var upStreamAminoAcids = GetFlankingPeptides(transcript.Translation?.PeptideSeq, proteinBegin, proteinEnd, FlankingAminoAcidLength, true);
var downStreamAminoAcids = consequences.Contains(ConsequenceTag.frameshift_variant)? null: GetFlankingPeptides(transcript.Translation?.PeptideSeq, proteinBegin, proteinEnd, FlankingAminoAcidLength, false);
return(new PianoAnnotatedTranscript(transcript, referenceAminoAcids, alternateAminoAcids, mappedPositions, upStreamAminoAcids, downStreamAminoAcids, consequences));
}
AltAminoAcids, string RefCodons, string AltCodons, string TranscriptAltAllele) AnnotateTranscript(ITranscript transcript, ISimpleVariant variant, AminoAcids aminoAcids,
ISequence refSequence)
{
var onReverseStrand = transcript.Gene.OnReverseStrand;
var start = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.Start);
var end = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.End);
var position = GetMappedPosition(transcript.TranscriptRegions, start.Region, start.Index, end.Region,
end.Index, variant, onReverseStrand, transcript.Translation?.CodingRegion, transcript.StartExonPhase,
variant.Type == VariantType.insertion);
var transcriptRefAllele = HgvsUtilities.GetTranscriptAllele(variant.RefAllele, onReverseStrand);
var transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, onReverseStrand);
var codingSequence = transcript.Translation == null
? null
: new CodingSequence(refSequence, transcript.Translation.CodingRegion, transcript.TranscriptRegions,
transcript.Gene.OnReverseStrand, transcript.StartExonPhase);
var codons = Codons.GetCodons(transcriptRefAllele, transcriptAltAllele, position.CdsStart, position.CdsEnd,
position.ProteinStart, position.ProteinEnd, codingSequence);
var coveredCdna = transcript.TranscriptRegions.GetCoveredCdnaPositions(position.CdnaStart, start.Index,
position.CdnaEnd, end.Index, onReverseStrand);
var coveredCds = MappedPositionUtilities.GetCoveredCdsPositions(coveredCdna.Start, coveredCdna.End,
transcript.StartExonPhase, transcript.Translation?.CodingRegion);
var aa = aminoAcids.Translate(codons.Reference, codons.Alternate);
var positionalEffect = GetPositionalEffect(transcript, variant, position, aa.Reference, aa.Alternate,
coveredCdna.Start, coveredCdna.End, coveredCds.Start, coveredCds.End);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, aa.Reference, aa.Alternate,
codons.Reference, codons.Alternate, position.ProteinStart);
return(variantEffect, position, aa.Reference, aa.Alternate, codons.Reference, codons.Alternate,
transcriptAltAllele);
}
private static string GetTranscriptRefAllele(IMappedPosition position, ISequence cdnaSequence, ISimpleVariant variant,
bool onReverseStrand)
{
var variantRef = HgvsUtilities.GetTranscriptAllele(variant.RefAllele, onReverseStrand);
if (position == null || cdnaSequence == null)
{
return(variantRef);
}
var start = position.CoveredCdnaStart;
var end = position.CoveredCdnaEnd;
if (start == -1 && end == -1)
{
return(variantRef);
}
if (start != -1 && end != -1 && end < start)
{
Swap.Int(ref start, ref end);
}
return(cdnaSequence.Substring(start - 1, end - start + 1));
}
