Check handling of early stops

[akotlar]

• Check that we are translating correctly (note that length shown includes introns, from cdsStart .. cdsEnd - 1)

[
    [0] "earlyStop;tx:76;name:NM_001291381;site:1155;codonN:253;cdsStart:13632347;cdsEnd:13635279,codon:TAG,len:2932"
]
MSLQAPSRLLELAGQSLLRNQFLTIFTLDELPREVFPLMFMEAFSMRRFEALKLMVQAWPFLRLPLGSLMKTPHLETLQAVLRGLDTLVAQKVRPRRWKLQVLDLRDVDENFWTIWSGARVLSCSPEAMSKRQTVEDCPRMGERQPLKVFIDLCLKESTLDECLSYLFGWIHYRRGLVHLCCSKVQNYSMPTSSFRNLLERIYPDSIQELEVWKKCSLNKTGKFAPYLSQMSNLRELFLAFGYERELYVSVQ*PCIPDLDSPFLCLYYPQMLYIKKISNIKEHLEHLLRYLKNPLGAFIFSDAYLADRDMECLSQYPSLSQLKELRLIHILMWTTHLEPLGVLLEKVAATLKTLVLKDCRIQDPQLRVLLPALSHCSQLTTFNFHGNETSMNALKDLLRHTRGLSKLGLELYPAPLESLDYKGHVNWEILTPIRAELMRTLREVRQPKRIFFGPVPCPTCGSWPSEKVDFHLCS*
[
    [0] "earlyStop;tx:77;name:NM_001039361;site:1155;codonN:253;cdsStart:13632347;cdsEnd:13635279,codon:TAG,len:2932"
]
MSLQAPSRLLELAGQSLLRNQFLTIFTLDELPREVFPLMFMEAFSMRRFEALKLMVQAWPFLRLPLGSLMKTPHLETLQAVLRGLDTLVAQKVRPRRWKLQVLDLRDVDENFWTIWSGARVLSCSPEAMSKRQTVEDCPRMGERQPLKVFIDLCLKESTLDECLSYLFGWIHYRRGLVHLCCSKVQNYSMPTSSFRNLLERIYPDSIQELEVWKKCSLNKTGKFAPYLSQMSNLRELFLAFGYERELYVSVQ*PCIPDLDSPFLCLYYPQMLYIKKISNIKEHLEHLLRYLKNPLGAFIFSDAYLADRDMECLSQYPSLSQLKELRLIHILMWTTHLEPLGVLLEKVAATLKTLVLKDCRIQDPQLRVLLPALSHCSQLTTFNFHGNETSMNALKDLLRHTRGLSKLGLELYPAPLESLDYKGHVNWEILTPIRAELMRTLREVRQPKRIFFGPVPCPTCGSWPSEKVDFHLCS*
[
    [0] "earlyStop;tx:2450;name:NM_001039361;site:1155;codonN:253;cdsStart:13411550;cdsEnd:13414482,codon:TAG,len:2932"
]
MSLQAPSRLLELAGQSLLRNQFLTIFTLDELPREVFPLMFMEAFSMRRFEALKLMVQAWPFLRLPLGSLMKTPHLETLQAVLRGLDTLVAQKVRPRRWKLQVLDLRDVDENFWTIWSGARVLSCSPEAMSKRQTVEDCPRMGERQPLKVFIDLCLKESTLDECLSYLFGWIHYRRGLVHLCCSKVQNYSMPTSSFRNLLERIYPDSIQELEVWKKCSLNKTGKFAPYLSQMSNLRELFLAFGYERELYVSVQ*PCIPDLDSPFLCLYYPQMLYIKKISNIKEHLEHLLRYLKNPLGAFIFSDAYLTDRDMECLSQYPSLSQLKELRLIHILMWTTNLEPLGVLLEKVAATLKTLVLKDCRIQDPQLRVLLPALSHCSQLTTFNFHGNETSMNALKDLLRHTRGLSKLGLELYPAPLESLDYKGHVNWEILTPIRAELMRTLREVRQPKRIFFGPVPCPTCGSWPSEKVDFHLCS*
[
    [0] "earlyStop;tx:2451;name:NM_001291381;site:1155;codonN:253;cdsStart:13411550;cdsEnd:13414482,codon:TAG,len:2932"
]
MSLQAPSRLLELAGQSLLRNQFLTIFTLDELPREVFPLMFMEAFSMRRFEALKLMVQAWPFLRLPLGSLMKTPHLETLQAVLRGLDTLVAQKVRPRRWKLQVLDLRDVDENFWTIWSGARVLSCSPEAMSKRQTVEDCPRMGERQPLKVFIDLCLKESTLDECLSYLFGWIHYRRGLVHLCCSKVQNYSMPTSSFRNLLERIYPDSIQELEVWKKCSLNKTGKFAPYLSQMSNLRELFLAFGYERELYVSVQ*PCIPDLDSPFLCLYYPQMLYIKKISNIKEHLEHLLRYLKNPLGAFIFSDAYLTDRDMECLSQYPSLSQLKELRLIHILMWTTNLEPLGVLLEKVAATLKTLVLKDCRIQDPQLRVLLPALSHCSQLTTFNFHGNETSMNALKDLLRHTRGLSKLGLELYPAPLESLDYKGHVNWEILTPIRAELMRTLREVRQPKRIFFGPVPCPTCGSWPSEKVDFHLCS*
[
    [0] "earlyStop;tx:2425;name:NM_001103170;site:39;codonN:13;cdsStart:12776179;cdsEnd:12785963,codon:TGA,len:9784"
]
MWDLALIFLAAA*VFSLGVTLWVICSHFFTVHIPAAVGHPVKLRVLHCIFQLLLTWGMIFEKLRICSMPQFFCFMQDLPPLKYDPDVVVTDFRFGTIPVKLYQSKASTCTLKPGIVYYHGGGGVMGSLKTHHGICSRLCKESDSVVLAVGYRKLPKHKFPVPVRDCLVATIHFLKSLDAYGVDPARVVVCGDSFGGAIAAVVCQQLVDRPDLPRIRAQILIYAILQALDLQTPSFQQRKNIPLLTWSFICYCFFQNLDFSSSWQEVIMKGAHLPAEVWEKYRKWLGPENIPERFKERGYQLKPHEPMNEAAYLEVSVVLDVMCSPLIAEDDIVSQLPETCIVSCEYDALRDNSLLYKKRLEDLGVPVTWHHMEDGFHGVLRTIDMSFLHFPCSMRILSALVQFVKGL*
[
    [0] "earlyStop;tx:2599;name:NM_001348421;site:3243;codonN:106;cdsStart:19593793;cdsEnd:19600568,codon:TGA,len:6775"
]
MSRQLSRARPATVLGAMEMGRRMDAPTSAAVTRAFLERGHTEIDTAFLYSDGQSETILGGLGLRMGSSDCRVKIATKANPWIGNSLKPDSVRSQLETSLKRLQCP*VDLFYLHAPDHSAPVEETLRACHQLHQEGKFVELGLSNYAAWEVAEICTLCKSNGWILPTVYQGMYSATTRQVETELFPCLRHFGLRFYAYNPLAGGLLTGKYKYEDKDGKQPVGRFFGTQWAEIYRNHFWKEHHFEGIALVEKALQAAYGASAPSMTSAALRWMYHHSQLQGAHGDAVILGMSSLEQLEQNLAAAEEGPLEPAVVDAFNQAWHLFAHECPNYFI*
[
    [0] "earlyStop;tx:2853;name:NM_206926;site:12561;codonN:428;cdsStart:26126721;cdsEnd:26142209,codon:TGA,len:15488"
]
MGRARPGQRGPPSPGPAAQPPAPPRRRARSLALLGALLAAAAAAAVRVCARHAEAQAAARQELALKTLGTDGLFLFSSLDTDGDMYISPEEFKPIAEKLTGSTPAASCEEEELPPDPSEETLTIEARFQPLLPETMTKSKDGFLGVSRLALSGLRNWTAAASPSAVFATRHFQPFLPPPGQELGEPWWIIPSELSMFTGYLSNNRFYPPPPKGKEVIIHRLLSMFHPRPFVKTRFAPQGAVACLTAISDFYYTVMFRIHAEFQLSEPPDFPFWFSPAQFTGHIILSKDATHVRDFRLFVPNHRSLNVDMEWLYGASESSNMEVDIGYIPQMELEATGPSVPSVILDEDGSMIDSHLPSGEPLQFVFEEIKWQQELSWEEAARRLEVAMYPFKKVSYLPFTEAFDRAKAENKLVHSILLWGALDDQSC*GSGRTLRETVLESSPILTLLNESFISTWSLVKELEELQNNQENSSHQKLAGLHLEKYSFPVEMMICLPNGTVVHHINANYFLDITSVKPEEIESNLFSFSSTFEDPSTATYMQFLKEGLRRGLPLLQP*
[
    [0] "earlyStop;tx:2856;name:NM_020451;site:1865;codonN:127;cdsStart:26126721;cdsEnd:26142209,codon:TGA,len:15488",
    [1] "earlyStop;tx:2856;name:NM_020451;site:12561;codonN:462;cdsStart:26126721;cdsEnd:26142209,codon:TGA,len:15488"
]
MGRARPGQRGPPSPGPAAQPPAPPRRRARSLALLGALLAAAAAAAVRVCARHAEAQAAARQELALKTLGTDGLFLFSSLDTDGDMYISPEEFKPIAEKLTGSCSVTQTGVQWCSHSSLQPQLPWLN*SSCLSLLRSTPAASCEEEELPPDPSEETLTIEARFQPLLPETMTKSKDGFLGVSRLALSGLRNWTAAASPSAVFATRHFQPFLPPPGQELGEPWWIIPSELSMFTGYLSNNRFYPPPPKGKEVIIHRLLSMFHPRPFVKTRFAPQGAVACLTAISDFYYTVMFRIHAEFQLSEPPDFPFWFSPAQFTGHIILSKDATHVRDFRLFVPNHRSLNVDMEWLYGASESSNMEVDIGYIPQMELEATGPSVPSVILDEDGSMIDSHLPSGEPLQFVFEEIKWQQELSWEEAARRLEVAMYPFKKVSYLPFTEAFDRAKAENKLVHSILLWGALDDQSC*GSGRTLRETVLESSPILTLLNESFISTWSLVKELEELQNNQENSSHQKLAGLHLEKYSFPVEMMICLPNGTVVHHINANYFLDITSVKPEEIESNLFSFSSTFEDPSTATYMQFLKEGLRRGLPLLQP*

• Define behavior when encountered (currently: output warnings)

[akotlar]

EarlyStopTx.xlsx
See attached excel file

[NM_001291381] (https://www.ncbi.nlm.nih.gov/nuccore/NM_001291381)

• 6 mismatches, including the early stop

NM_001103170/ NP_001096640.2

• 3 mismatches, including the early stop (at codon #13!!)
• Seems it may be a hg19 patch version issue; we are using on hg19 the original sequence, rather than p13, which is what UCSC seems to be using for translation
• The UCSC knownGenes result is also different from the refSeq tx, and dramatically so. (it is 59 codons shorter):
  • knownGene vs refSeq

[akotlar]

Looking in UCSC, see attached; we don't know the protein revision, could predate the versions seen on RefSeq.

NM_001291381 (earliest available on NCBI is the .2 accession)

mysql> SELECT r.*, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.kgID, '')) SEPARATOR           ';') FROM kgXref x WHERE x.refseq=r.name) AS kgID, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.description,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS description,           (SELECT GROUP_CONCAT(DISTINCT(NULLIF(e.value, '')) SEPARATOR ';') FROM knownToEnsembl           e JOIN kgXref x ON x.kgID = e.name WHERE x.refsname) AS ensemblID,           (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.tRnaName, '')) SEPARATOR ';') FROM           kgXref x WHERE x.refseq=r.name) AS tRnaName, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.spID,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS spID, (SELECT           GROUP_CONCAT(DISTINCT(NULLIF(x.spDisplayID, '')) SEPARATOR ';') FROM kgXref           x WHERE x.refseq=r.name) AS spDisplayID, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.protAcc,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS protAcc, (SELECT           GROUP_CONCAT(DISTINCT(NULLIF(x.mRNA, '')) SEPARATOR ';') FROM kgXref x WHERE           x.refseq=r.name) AS mRNA, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.rfamAcc,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS rfamAcc FROM           refGene r WHERE r.name='NM_001039361' OR r.name='NM_001291381';

NM_001103170

SELECT r.*, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.kgID, '')) SEPARATOR           ';') FROM kgXref x WHERE x.refseq=r.name) AS kgID, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.description,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS description,           (SELECT GROUP_CONCAT(DISTINCT(NULLIF(e.value, '')) SEPARATOR ';') FROM knownToEnsembl           e JOIN kgXref x ON x.kgID = e.name WHERE x.refseq = r.name) AS ensemblID,           (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.tRnaName, '')) SEPARATOR ';') FROM           kgXref x WHERE x.refseq=r.name) AS tRnaName, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.spID,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS spID, (SELECT           GROUP_CONCAT(DISTINCT(NULLIF(x.spDisplayID, '')) SEPARATOR ';') FROM kgXref           x WHERE x.refseq=r.name) AS spDisplayID, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.protAcc,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS protAcc, (SELECT           GROUP_CONCAT(DISTINCT(NULLIF(x.mRNA, '')) SEPARATOR ';') FROM kgXref x WHERE           x.refseq=r.name) AS mRNA, (SELECT GROUP_CONCAT(DISTINCT(NULLIF(x.rfamAcc,           '')) SEPARATOR ';') FROM kgXref x WHERE x.refseq=r.name) AS rfamAcc FROM           refGene r WHERE r.name='NM_001103170';