PubMed:19094116 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/19094116","sourcedb":"PubMed","sourceid":"19094116","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/19094116","text":"Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor secretion is impaired in Crohn's disease by nucleotide oligomerization domain 2-dependent and -independent pathways.\nPattern recognition receptors (PRRs) are an integral part of the innate immune system and govern the early control of foreign microorganisms. Single nucleotide polymorphisms (SNPs) in the intracellular pattern recognition receptor nucleotide-binding oligomerization domain-containing protein (NOD2, nucleotide oligomerization domain 2) are associated with Crohn's disease (CD). We investigated the impact of NOD2 polymorphisms on cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) in response to Toll-like receptor (TLR) and NOD2 ligands. Based on NOD2 SNP analyses, 41 CD patients and 12 healthy controls were studied. PBMCs were stimulated with NOD2 and TLR ligands. After 18 h culture supernatants were measured using multiplex assays for the presence of human cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha. In CD patients, TLR-induced GM-CSF secretion was impaired by both NOD2-dependent and -independent mechanisms. Moreover, TNF-alpha production was induced by a TLR-2 ligand, but a down-regulatory function by the NOD2 ligand, muramyl dipeptide, was impaired significantly in CD patients. Intracellular TLR ligands had minimal effect on GM-CSF, TNF-alpha and IL-1beta secretion. CD patients with NOD2 mutations were able to secrete TNF-alpha, but not GM-CSF, upon stimulation with NOD2 and TLR-7 ligands. CD patients have impaired GM-CSF secretion via NOD2-dependent and -independent pathways and display an impaired NOD2-dependent down-regulation of TNF-alpha secretion. The defect in GM-CSF secretion suggests a hitherto unknown role of NOD2 in the pathogenesis of CD and is consistent with the hypothesis that impaired GM-CSF secretion in part constitutes a NOD2-dependent disease risk factor.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":27,"end":75},"obj":"gene:1437"},{"id":"T1","span":{"begin":101,"end":106},"obj":"disease:C0010346"},{"id":"T2","span":{"begin":486,"end":490},"obj":"gene:64127"},{"id":"T3","span":{"begin":549,"end":554},"obj":"disease:C0010346"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"19094116-0#27#75#gene1437","span":{"begin":27,"end":75},"obj":"gene1437"},{"id":"19094116-0#101#116#diseaseC0010346","span":{"begin":101,"end":116},"obj":"diseaseC0010346"},{"id":"19094116-12#67#71#gene64127","span":{"begin":1857,"end":1861},"obj":"gene64127"},{"id":"19094116-12#189#193#gene64127","span":{"begin":1979,"end":1983},"obj":"gene64127"},{"id":"19094116-12#95#97#diseaseC0010346","span":{"begin":1885,"end":1887},"obj":"diseaseC0010346"}],"relations":[{"id":"27#75#gene1437101#116#diseaseC0010346","pred":"associated_with","subj":"19094116-0#27#75#gene1437","obj":"19094116-0#101#116#diseaseC0010346"},{"id":"67#71#gene6412795#97#diseaseC0010346","pred":"associated_with","subj":"19094116-12#67#71#gene64127","obj":"19094116-12#95#97#diseaseC0010346"},{"id":"189#193#gene6412795#97#diseaseC0010346","pred":"associated_with","subj":"19094116-12#189#193#gene64127","obj":"19094116-12#95#97#diseaseC0010346"}],"attributes":[{"subj":"19094116-0#27#75#gene1437","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19094116-0#101#116#diseaseC0010346","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19094116-12#67#71#gene64127","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19094116-12#189#193#gene64127","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19094116-12#95#97#diseaseC0010346","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":0,"end":75},"obj":"GENE"},{"id":"T1","span":{"begin":27,"end":75},"obj":"GENE"},{"id":"T2","span":{"begin":76,"end":85},"obj":"MPA"},{"id":"T3","span":{"begin":89,"end":97},"obj":"NEGREG"},{"id":"T4","span":{"begin":101,"end":116},"obj":"DISEASE"},{"id":"T5","span":{"begin":120,"end":165},"obj":"GENE"},{"id":"T6","span":{"begin":283,"end":289},"obj":"REG"},{"id":"T7","span":{"begin":353,"end":366},"obj":"VAR"},{"id":"T8","span":{"begin":368,"end":372},"obj":"VAR"},{"id":"T9","span":{"begin":486,"end":490},"obj":"GENE"},{"id":"T10","span":{"begin":492,"end":527},"obj":"GENE"},{"id":"T11","span":{"begin":533,"end":543},"obj":"REG"},{"id":"T12","span":{"begin":549,"end":564},"obj":"DISEASE"},{"id":"T13","span":{"begin":566,"end":568},"obj":"DISEASE"},{"id":"T14","span":{"begin":591,"end":597},"obj":"REG"},{"id":"T15","span":{"begin":601,"end":605},"obj":"GENE"},{"id":"T16","span":{"begin":606,"end":619},"obj":"VAR"},{"id":"T17","span":{"begin":623,"end":641},"obj":"MPA"},{"id":"T18","span":{"begin":646,"end":659},"obj":"CPA"},{"id":"T19","span":{"begin":699,"end":704},"obj":"CPA"},{"id":"T20","span":{"begin":709,"end":717},"obj":"REG"},{"id":"T21","span":{"begin":741,"end":744},"obj":"GENE"},{"id":"T22","span":{"begin":750,"end":754},"obj":"GENE"},{"id":"T23","span":{"begin":750,"end":754},"obj":"GENE"},{"id":"T24","span":{"begin":755,"end":762},"obj":"MPA"},{"id":"T25","span":{"begin":773,"end":777},"obj":"GENE"},{"id":"T26","span":{"begin":778,"end":781},"obj":"VAR"},{"id":"T27","span":{"begin":795,"end":797},"obj":"DISEASE"},{"id":"T28","span":{"begin":856,"end":866},"obj":"REG"},{"id":"T29","span":{"begin":872,"end":876},"obj":"GENE"},{"id":"T30","span":{"begin":872,"end":876},"obj":"GENE"},{"id":"T31","span":{"begin":881,"end":884},"obj":"GENE"},{"id":"T32","span":{"begin":971,"end":979},"obj":"MPA"},{"id":"T33","span":{"begin":999,"end":1047},"obj":"GENE"},{"id":"T34","span":{"begin":999,"end":1047},"obj":"GENE"},{"id":"T35","span":{"begin":1049,"end":1055},"obj":"GENE"},{"id":"T36","span":{"begin":1049,"end":1055},"obj":"GENE"},{"id":"T37","span":{"begin":1058,"end":1081},"obj":"GENE"},{"id":"T38","span":{"begin":1058,"end":1081},"obj":"GENE"},{"id":"T39","span":{"begin":1086,"end":1120},"obj":"GENE"},{"id":"T40","span":{"begin":1086,"end":1120},"obj":"GENE"},{"id":"T41","span":{"begin":1125,"end":1127},"obj":"DISEASE"},{"id":"T42","span":{"begin":1150,"end":1156},"obj":"GENE"},{"id":"T43","span":{"begin":1150,"end":1156},"obj":"GENE"},{"id":"T44","span":{"begin":1157,"end":1166},"obj":"MPA"},{"id":"T45","span":{"begin":1171,"end":1179},"obj":"NEGREG"},{"id":"T46","span":{"begin":1188,"end":1202},"obj":"GENE"},{"id":"T47","span":{"begin":1188,"end":1202},"obj":"GENE"},{"id":"T48","span":{"begin":1207,"end":1230},"obj":"MPA"},{"id":"T49","span":{"begin":1242,"end":1251},"obj":"GENE"},{"id":"T50","span":{"begin":1242,"end":1251},"obj":"GENE"},{"id":"T51","span":{"begin":1252,"end":1262},"obj":"MPA"},{"id":"T52","span":{"begin":1267,"end":1274},"obj":"POSREG"},{"id":"T53","span":{"begin":1280,"end":1285},"obj":"GENE"},{"id":"T54","span":{"begin":1280,"end":1285},"obj":"GENE"},{"id":"T55","span":{"begin":1286,"end":1292},"obj":"MPA"},{"id":"T56","span":{"begin":1300,"end":1315},"obj":"NEGREG"},{"id":"T57","span":{"begin":1316,"end":1324},"obj":"MPA"},{"id":"T58","span":{"begin":1332,"end":1336},"obj":"GENE"},{"id":"T59","span":{"begin":1332,"end":1336},"obj":"GENE"},{"id":"T60","span":{"begin":1337,"end":1343},"obj":"MPA"},{"id":"T61","span":{"begin":1345,"end":1362},"obj":"MPA"},{"id":"T62","span":{"begin":1368,"end":1376},"obj":"NEGREG"},{"id":"T63","span":{"begin":1394,"end":1396},"obj":"DISEASE"},{"id":"T64","span":{"begin":1407,"end":1432},"obj":"MPA"},{"id":"T65","span":{"begin":1437,"end":1444},"obj":"NEGREG"},{"id":"T66","span":{"begin":1445,"end":1451},"obj":"REG"},{"id":"T67","span":{"begin":1455,"end":1461},"obj":"GENE"},{"id":"T68","span":{"begin":1455,"end":1461},"obj":"GENE"},{"id":"T69","span":{"begin":1463,"end":1472},"obj":"GENE"},{"id":"T70","span":{"begin":1463,"end":1472},"obj":"GENE"},{"id":"T71","span":{"begin":1477,"end":1485},"obj":"GENE"},{"id":"T72","span":{"begin":1477,"end":1485},"obj":"GENE"},{"id":"T73","span":{"begin":1486,"end":1495},"obj":"MPA"},{"id":"T74","span":{"begin":1497,"end":1499},"obj":"DISEASE"},{"id":"T75","span":{"begin":1514,"end":1518},"obj":"GENE"},{"id":"T76","span":{"begin":1519,"end":1528},"obj":"VAR"},{"id":"T77","span":{"begin":1534,"end":1538},"obj":"REG"},{"id":"T78","span":{"begin":1542,"end":1549},"obj":"MPA"},{"id":"T79","span":{"begin":1550,"end":1559},"obj":"GENE"},{"id":"T80","span":{"begin":1550,"end":1559},"obj":"GENE"},{"id":"T81","span":{"begin":1569,"end":1575},"obj":"GENE"},{"id":"T82","span":{"begin":1569,"end":1575},"obj":"GENE"},{"id":"T83","span":{"begin":1599,"end":1603},"obj":"GENE"},{"id":"T84","span":{"begin":1599,"end":1603},"obj":"GENE"},{"id":"T85","span":{"begin":1608,"end":1613},"obj":"GENE"},{"id":"T86","span":{"begin":1608,"end":1613},"obj":"GENE"},{"id":"T87","span":{"begin":1614,"end":1621},"obj":"MPA"},{"id":"T88","span":{"begin":1623,"end":1625},"obj":"DISEASE"},{"id":"T89","span":{"begin":1640,"end":1648},"obj":"NEGREG"},{"id":"T90","span":{"begin":1649,"end":1655},"obj":"GENE"},{"id":"T91","span":{"begin":1649,"end":1655},"obj":"GENE"},{"id":"T92","span":{"begin":1656,"end":1665},"obj":"MPA"},{"id":"T93","span":{"begin":1670,"end":1684},"obj":"GENE"},{"id":"T94","span":{"begin":1670,"end":1684},"obj":"GENE"},{"id":"T95","span":{"begin":1715,"end":1722},"obj":"REG"},{"id":"T96","span":{"begin":1726,"end":1734},"obj":"NEGREG"},{"id":"T97","span":{"begin":1735,"end":1749},"obj":"GENE"},{"id":"T98","span":{"begin":1735,"end":1749},"obj":"GENE"},{"id":"T99","span":{"begin":1750,"end":1765},"obj":"NEGREG"},{"id":"T100","span":{"begin":1769,"end":1778},"obj":"GENE"},{"id":"T101","span":{"begin":1779,"end":1788},"obj":"MPA"},{"id":"T102","span":{"begin":1794,"end":1800},"obj":"NEGREG"},{"id":"T103","span":{"begin":1804,"end":1810},"obj":"GENE"},{"id":"T104","span":{"begin":1804,"end":1810},"obj":"GENE"},{"id":"T105","span":{"begin":1811,"end":1820},"obj":"MPA"},{"id":"T106","span":{"begin":1821,"end":1829},"obj":"REG"},{"id":"T107","span":{"begin":1849,"end":1853},"obj":"REG"},{"id":"T108","span":{"begin":1857,"end":1861},"obj":"GENE"},{"id":"T109","span":{"begin":1869,"end":1881},"obj":"CPA"},{"id":"T110","span":{"begin":1885,"end":1887},"obj":"DISEASE"},{"id":"T111","span":{"begin":1931,"end":1939},"obj":"NEGREG"},{"id":"T112","span":{"begin":1940,"end":1946},"obj":"GENE"},{"id":"T113","span":{"begin":1940,"end":1946},"obj":"GENE"},{"id":"T114","span":{"begin":1947,"end":1956},"obj":"MPA"},{"id":"T115","span":{"begin":1965,"end":1976},"obj":"REG"},{"id":"T116","span":{"begin":1979,"end":1993},"obj":"GENE"},{"id":"T117","span":{"begin":1994,"end":2013},"obj":"MPA"}],"relations":[{"id":"R144","pred":"ThemeOf","subj":"T108","obj":"T109"},{"id":"R145","pred":"ThemeOf","subj":"T109","obj":"T106"},{"id":"R146","pred":"ThemeOf","subj":"T110","obj":"T109"},{"id":"R147","pred":"ThemeOf","subj":"T110","obj":"T106"},{"id":"R148","pred":"ThemeOf","subj":"T110","obj":"T107"},{"id":"R149","pred":"ThemeOf","subj":"T114","obj":"T111"},{"id":"R150","pred":"ThemeOf","subj":"T112","obj":"T111"},{"id":"R151","pred":"ThemeOf","subj":"T112","obj":"T114"},{"id":"R152","pred":"ThemeOf","subj":"T112","obj":"T115"},{"id":"R153","pred":"ThemeOf","subj":"T114","obj":"T115"},{"id":"R154","pred":"ThemeOf","subj":"T114","obj":"T117"},{"id":"R155","pred":"ThemeOf","subj":"T117","obj":"T115"},{"id":"R0","pred":"ThemeOf","subj":"T0","obj":"T2"},{"id":"R1","pred":"ThemeOf","subj":"T0","obj":"T3"},{"id":"R2","pred":"ThemeOf","subj":"T2","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T2"},{"id":"R4","pred":"ThemeOf","subj":"T4","obj":"T3"},{"id":"R5","pred":"CauseOf","subj":"T7","obj":"T11"},{"id":"R6","pred":"CauseOf","subj":"T8","obj":"T11"},{"id":"R7","pred":"ThemeOf","subj":"T12","obj":"T8"},{"id":"R8","pred":"ThemeOf","subj":"T9","obj":"T7"},{"id":"R9","pred":"ThemeOf","subj":"T9","obj":"T8"},{"id":"R10","pred":"ThemeOf","subj":"T9","obj":"T11"},{"id":"R11","pred":"ThemeOf","subj":"T10","obj":"T7"},{"id":"R12","pred":"ThemeOf","subj":"T10","obj":"T8"},{"id":"R13","pred":"ThemeOf","subj":"T10","obj":"T11"},{"id":"R14","pred":"ThemeOf","subj":"T12","obj":"T11"},{"id":"R15","pred":"ThemeOf","subj":"T13","obj":"T11"},{"id":"R16","pred":"ThemeOf","subj":"T15","obj":"T14"},{"id":"R17","pred":"ThemeOf","subj":"T14","obj":"T16"},{"id":"R18","pred":"ThemeOf","subj":"T17","obj":"T14"},{"id":"R19","pred":"ThemeOf","subj":"T15","obj":"T16"},{"id":"R20","pred":"ThemeOf","subj":"T15","obj":"T17"},{"id":"R21","pred":"ThemeOf","subj":"T15","obj":"T24"},{"id":"R22","pred":"ThemeOf","subj":"T17","obj":"T16"},{"id":"R23","pred":"ThemeOf","subj":"T18","obj":"T16"},{"id":"R24","pred":"ThemeOf","subj":"T17","obj":"T20"},{"id":"R25","pred":"ThemeOf","subj":"T17","obj":"T24"},{"id":"R26","pred":"ThemeOf","subj":"T18","obj":"T14"},{"id":"R27","pred":"ThemeOf","subj":"T18","obj":"T20"},{"id":"R28","pred":"ThemeOf","subj":"T18","obj":"T24"},{"id":"R29","pred":"ThemeOf","subj":"T19","obj":"T14"},{"id":"R30","pred":"ThemeOf","subj":"T19","obj":"T20"},{"id":"R31","pred":"ThemeOf","subj":"T19","obj":"T24"},{"id":"R32","pred":"ThemeOf","subj":"T20","obj":"T24"},{"id":"R33","pred":"ThemeOf","subj":"T21","obj":"T20"},{"id":"R34","pred":"ThemeOf","subj":"T21","obj":"T24"},{"id":"R35","pred":"ThemeOf","subj":"T22","obj":"T16"},{"id":"R36","pred":"ThemeOf","subj":"T22","obj":"T20"},{"id":"R37","pred":"ThemeOf","subj":"T22","obj":"T24"},{"id":"R38","pred":"ThemeOf","subj":"T25","obj":"T24"},{"id":"R39","pred":"ThemeOf","subj":"T25","obj":"T26"},{"id":"R40","pred":"ThemeOf","subj":"T27","obj":"T26"},{"id":"R41","pred":"ThemeOf","subj":"T29","obj":"T28"},{"id":"R42","pred":"ThemeOf","subj":"T29","obj":"T32"},{"id":"R43","pred":"ThemeOf","subj":"T31","obj":"T28"},{"id":"R44","pred":"ThemeOf","subj":"T32","obj":"T28"},{"id":"R45","pred":"ThemeOf","subj":"T33","obj":"T32"},{"id":"R46","pred":"ThemeOf","subj":"T33","obj":"T28"},{"id":"R47","pred":"ThemeOf","subj":"T35","obj":"T28"},{"id":"R48","pred":"ThemeOf","subj":"T35","obj":"T32"},{"id":"R49","pred":"ThemeOf","subj":"T37","obj":"T28"},{"id":"R50","pred":"ThemeOf","subj":"T37","obj":"T32"},{"id":"R51","pred":"ThemeOf","subj":"T39","obj":"T28"},{"id":"R52","pred":"ThemeOf","subj":"T39","obj":"T32"},{"id":"R53","pred":"ThemeOf","subj":"T41","obj":"T44"},{"id":"R54","pred":"ThemeOf","subj":"T41","obj":"T45"},{"id":"R55","pred":"ThemeOf","subj":"T42","obj":"T44"},{"id":"R56","pred":"ThemeOf","subj":"T42","obj":"T45"},{"id":"R57","pred":"ThemeOf","subj":"T44","obj":"T45"},{"id":"R58","pred":"ThemeOf","subj":"T44","obj":"T48"},{"id":"R59","pred":"ThemeOf","subj":"T48","obj":"T45"},{"id":"R60","pred":"ThemeOf","subj":"T46","obj":"T48"},{"id":"R61","pred":"ThemeOf","subj":"T49","obj":"T51"},{"id":"R62","pred":"ThemeOf","subj":"T49","obj":"T52"},{"id":"R63","pred":"ThemeOf","subj":"T49","obj":"T55"},{"id":"R64","pred":"ThemeOf","subj":"T51","obj":"T52"},{"id":"R65","pred":"ThemeOf","subj":"T51","obj":"T55"},{"id":"R66","pred":"CauseOf","subj":"T55","obj":"T52"},{"id":"R67","pred":"ThemeOf","subj":"T53","obj":"T55"},{"id":"R68","pred":"ThemeOf","subj":"T57","obj":"T56"},{"id":"R69","pred":"ThemeOf","subj":"T56","obj":"T60"},{"id":"R70","pred":"ThemeOf","subj":"T58","obj":"T57"},{"id":"R71","pred":"ThemeOf","subj":"T57","obj":"T60"},{"id":"R72","pred":"ThemeOf","subj":"T57","obj":"T62"},{"id":"R73","pred":"ThemeOf","subj":"T58","obj":"T56"},{"id":"R74","pred":"ThemeOf","subj":"T58","obj":"T60"},{"id":"R75","pred":"CauseOf","subj":"T60","obj":"T52"},{"id":"R76","pred":"CauseOf","subj":"T60","obj":"T62"},{"id":"R77","pred":"ThemeOf","subj":"T61","obj":"T57"},{"id":"R78","pred":"ThemeOf","subj":"T61","obj":"T60"},{"id":"R79","pred":"ThemeOf","subj":"T63","obj":"T62"},{"id":"R80","pred":"ThemeOf","subj":"T66","obj":"T65"},{"id":"R81","pred":"ThemeOf","subj":"T73","obj":"T66"},{"id":"R82","pred":"ThemeOf","subj":"T67","obj":"T64"},{"id":"R83","pred":"ThemeOf","subj":"T67","obj":"T65"},{"id":"R84","pred":"ThemeOf","subj":"T67","obj":"T66"},{"id":"R85","pred":"ThemeOf","subj":"T67","obj":"T73"},{"id":"R86","pred":"ThemeOf","subj":"T69","obj":"T64"},{"id":"R87","pred":"ThemeOf","subj":"T69","obj":"T65"},{"id":"R88","pred":"ThemeOf","subj":"T69","obj":"T66"},{"id":"R89","pred":"ThemeOf","subj":"T69","obj":"T73"},{"id":"R90","pred":"ThemeOf","subj":"T71","obj":"T64"},{"id":"R91","pred":"ThemeOf","subj":"T71","obj":"T65"},{"id":"R92","pred":"ThemeOf","subj":"T71","obj":"T66"},{"id":"R93","pred":"ThemeOf","subj":"T71","obj":"T73"},{"id":"R94","pred":"ThemeOf","subj":"T73","obj":"T65"},{"id":"R95","pred":"ThemeOf","subj":"T74","obj":"T76"},{"id":"R96","pred":"ThemeOf","subj":"T74","obj":"T77"},{"id":"R97","pred":"ThemeOf","subj":"T74","obj":"T78"},{"id":"R98","pred":"ThemeOf","subj":"T75","obj":"T76"},{"id":"R99","pred":"ThemeOf","subj":"T75","obj":"T77"},{"id":"R100","pred":"ThemeOf","subj":"T75","obj":"T78"},{"id":"R101","pred":"ThemeOf","subj":"T75","obj":"T87"},{"id":"R102","pred":"CauseOf","subj":"T76","obj":"T77"},{"id":"R103","pred":"CauseOf","subj":"T76","obj":"T78"},{"id":"R104","pred":"ThemeOf","subj":"T78","obj":"T77"},{"id":"R105","pred":"ThemeOf","subj":"T79","obj":"T76"},{"id":"R106","pred":"ThemeOf","subj":"T79","obj":"T77"},{"id":"R107","pred":"ThemeOf","subj":"T79","obj":"T78"},{"id":"R108","pred":"ThemeOf","subj":"T79","obj":"T87"},{"id":"R109","pred":"ThemeOf","subj":"T81","obj":"T77"},{"id":"R110","pred":"ThemeOf","subj":"T81","obj":"T78"},{"id":"R111","pred":"ThemeOf","subj":"T81","obj":"T87"},{"id":"R112","pred":"ThemeOf","subj":"T83","obj":"T78"},{"id":"R113","pred":"ThemeOf","subj":"T83","obj":"T87"},{"id":"R114","pred":"ThemeOf","subj":"T85","obj":"T78"},{"id":"R115","pred":"ThemeOf","subj":"T85","obj":"T87"},{"id":"R116","pred":"ThemeOf","subj":"T88","obj":"T89"},{"id":"R117","pred":"ThemeOf","subj":"T92","obj":"T89"},{"id":"R118","pred":"CauseOf","subj":"T96","obj":"T89"},{"id":"R119","pred":"ThemeOf","subj":"T90","obj":"T89"},{"id":"R120","pred":"ThemeOf","subj":"T90","obj":"T92"},{"id":"R121","pred":"ThemeOf","subj":"T92","obj":"T95"},{"id":"R122","pred":"ThemeOf","subj":"T92","obj":"T96"},{"id":"R123","pred":"ThemeOf","subj":"T96","obj":"T95"},{"id":"R124","pred":"ThemeOf","subj":"T99","obj":"T96"},{"id":"R125","pred":"ThemeOf","subj":"T99","obj":"T97"},{"id":"R126","pred":"ThemeOf","subj":"T99","obj":"T95"},{"id":"R127","pred":"ThemeOf","subj":"T101","obj":"T99"},{"id":"R128","pred":"ThemeOf","subj":"T101","obj":"T95"},{"id":"R129","pred":"ThemeOf","subj":"T101","obj":"T96"},{"id":"R130","pred":"ThemeOf","subj":"T105","obj":"T102"},{"id":"R131","pred":"CauseOf","subj":"T102","obj":"T109"},{"id":"R132","pred":"CauseOf","subj":"T102","obj":"T111"},{"id":"R133","pred":"ThemeOf","subj":"T103","obj":"T102"},{"id":"R134","pred":"ThemeOf","subj":"T103","obj":"T105"},{"id":"R135","pred":"ThemeOf","subj":"T103","obj":"T106"},{"id":"R136","pred":"ThemeOf","subj":"T103","obj":"T107"},{"id":"R137","pred":"ThemeOf","subj":"T105","obj":"T106"},{"id":"R138","pred":"ThemeOf","subj":"T105","obj":"T107"},{"id":"R139","pred":"ThemeOf","subj":"T107","obj":"T106"},{"id":"R140","pred":"ThemeOf","subj":"T108","obj":"T107"},{"id":"R141","pred":"ThemeOf","subj":"T109","obj":"T107"},{"id":"R142","pred":"ThemeOf","subj":"T108","obj":"T105"},{"id":"R143","pred":"ThemeOf","subj":"T108","obj":"T106"}],"attributes":[{"subj":"T0","pred":"source","obj":"sonoma2"},{"subj":"T1","pred":"source","obj":"sonoma2"},{"subj":"T2","pred":"source","obj":"sonoma2"},{"subj":"T3","pred":"source","obj":"sonoma2"},{"subj":"T4","pred":"source","obj":"sonoma2"},{"subj":"T5","pred":"source","obj":"sonoma2"},{"subj":"T6","pred":"source","obj":"sonoma2"},{"subj":"T7","pred":"source","obj":"sonoma2"},{"subj":"T8","pred":"source","obj":"sonoma2"},{"subj":"T9","pred":"source","obj":"sonoma2"},{"subj":"T10","pred":"source","obj":"sonoma2"},{"subj":"T11","pred":"source","obj":"sonoma2"},{"subj":"T12","pred":"source","obj":"sonoma2"},{"subj":"T13","pred":"source","obj":"sonoma2"},{"subj":"T14","pred":"source","obj":"sonoma2"},{"subj":"T15","pred":"source","obj":"sonoma2"},{"subj":"T16","pred":"source","obj":"sonoma2"},{"subj":"T17","pred":"source","obj":"sonoma2"},{"subj":"T18","pred":"source","obj":"sonoma2"},{"subj":"T19","pred":"source","obj":"sonoma2"},{"subj":"T20","pred":"source","obj":"sonoma2"},{"subj":"T21","pred":"source","obj":"sonoma2"},{"subj":"T22","pred":"source","obj":"sonoma2"},{"subj":"T23","pred":"source","obj":"sonoma2"},{"subj":"T24","pred":"source","obj":"sonoma2"},{"subj":"T25","pred":"source","obj":"sonoma2"},{"subj":"T26","pred":"source","obj":"sonoma2"},{"subj":"T27","pred":"source","obj":"sonoma2"},{"subj":"T28","pred":"source","obj":"sonoma2"},{"subj":"T29","pred":"source","obj":"sonoma2"},{"subj":"T30","pred":"source","obj":"sonoma2"},{"subj":"T31","pred":"source","obj":"sonoma2"},{"subj":"T32","pred":"source","obj":"sonoma2"},{"subj":"T33","pred":"source","obj":"sonoma2"},{"subj":"T34","pred":"source","obj":"sonoma2"},{"subj":"T35","pred":"source","obj":"sonoma2"},{"subj":"T36","pred":"source","obj":"sonoma2"},{"subj":"T37","pred":"source","obj":"sonoma2"},{"subj":"T38","pred":"source","obj":"sonoma2"},{"subj":"T39","pred":"source","obj":"sonoma2"},{"subj":"T40","pred":"source","obj":"sonoma2"},{"subj":"T41","pred":"source","obj":"sonoma2"},{"subj":"T42","pred":"source","obj":"sonoma2"},{"subj":"T43","pred":"source","obj":"sonoma2"},{"subj":"T44","pred":"source","obj":"sonoma2"},{"subj":"T45","pred":"source","obj":"sonoma2"},{"subj":"T46","pred":"source","obj":"sonoma2"},{"subj":"T47","pred":"source","obj":"sonoma2"},{"subj":"T48","pred":"source","obj":"sonoma2"},{"subj":"T49","pred":"source","obj":"sonoma2"},{"subj":"T50","pred":"source","obj":"sonoma2"},{"subj":"T51","pred":"source","obj":"sonoma2"},{"subj":"T52","pred":"source","obj":"sonoma2"},{"subj":"T53","pred":"source","obj":"sonoma2"},{"subj":"T54","pred":"source","obj":"sonoma2"},{"subj":"T55","pred":"source","obj":"sonoma2"},{"subj":"T56","pred":"source","obj":"sonoma2"},{"subj":"T57","pred":"source","obj":"sonoma2"},{"subj":"T58","pred":"source","obj":"sonoma2"},{"subj":"T59","pred":"source","obj":"sonoma2"},{"subj":"T60","pred":"source","obj":"sonoma2"},{"subj":"T61","pred":"source","obj":"sonoma2"},{"subj":"T62","pred":"source","obj":"sonoma2"},{"subj":"T63","pred":"source","obj":"sonoma2"},{"subj":"T64","pred":"source","obj":"sonoma2"},{"subj":"T65","pred":"source","obj":"sonoma2"},{"subj":"T66","pred":"source","obj":"sonoma2"},{"subj":"T67","pred":"source","obj":"sonoma2"},{"subj":"T68","pred":"source","obj":"sonoma2"},{"subj":"T69","pred":"source","obj":"sonoma2"},{"subj":"T70","pred":"source","obj":"sonoma2"},{"subj":"T71","pred":"source","obj":"sonoma2"},{"subj":"T72","pred":"source","obj":"sonoma2"},{"subj":"T73","pred":"source","obj":"sonoma2"},{"subj":"T74","pred":"source","obj":"sonoma2"},{"subj":"T75","pred":"source","obj":"sonoma2"},{"subj":"T76","pred":"source","obj":"sonoma2"},{"subj":"T77","pred":"source","obj":"sonoma2"},{"subj":"T78","pred":"source","obj":"sonoma2"},{"subj":"T79","pred":"source","obj":"sonoma2"},{"subj":"T80","pred":"source","obj":"sonoma2"},{"subj":"T81","pred":"source","obj":"sonoma2"},{"subj":"T82","pred":"source","obj":"sonoma2"},{"subj":"T83","pred":"source","obj":"sonoma2"},{"subj":"T84","pred":"source","obj":"sonoma2"},{"subj":"T85","pred":"source","obj":"sonoma2"},{"subj":"T86","pred":"source","obj":"sonoma2"},{"subj":"T87","pred":"source","obj":"sonoma2"},{"subj":"T88","pred":"source","obj":"sonoma2"},{"subj":"T89","pred":"source","obj":"sonoma2"},{"subj":"T90","pred":"source","obj":"sonoma2"},{"subj":"T91","pred":"source","obj":"sonoma2"},{"subj":"T92","pred":"source","obj":"sonoma2"},{"subj":"T93","pred":"source","obj":"sonoma2"},{"subj":"T94","pred":"source","obj":"sonoma2"},{"subj":"T95","pred":"source","obj":"sonoma2"},{"subj":"T96","pred":"source","obj":"sonoma2"},{"subj":"T97","pred":"source","obj":"sonoma2"},{"subj":"T98","pred":"source","obj":"sonoma2"},{"subj":"T99","pred":"source","obj":"sonoma2"},{"subj":"T100","pred":"source","obj":"sonoma2"},{"subj":"T101","pred":"source","obj":"sonoma2"},{"subj":"T102","pred":"source","obj":"sonoma2"},{"subj":"T103","pred":"source","obj":"sonoma2"},{"subj":"T104","pred":"source","obj":"sonoma2"},{"subj":"T105","pred":"source","obj":"sonoma2"},{"subj":"T106","pred":"source","obj":"sonoma2"},{"subj":"T107","pred":"source","obj":"sonoma2"},{"subj":"T108","pred":"source","obj":"sonoma2"},{"subj":"T109","pred":"source","obj":"sonoma2"},{"subj":"T110","pred":"source","obj":"sonoma2"},{"subj":"T111","pred":"source","obj":"sonoma2"},{"subj":"T112","pred":"source","obj":"sonoma2"},{"subj":"T113","pred":"source","obj":"sonoma2"},{"subj":"T114","pred":"source","obj":"sonoma2"},{"subj":"T115","pred":"source","obj":"sonoma2"},{"subj":"T116","pred":"source","obj":"sonoma2"},{"subj":"T117","pred":"source","obj":"sonoma2"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":101,"end":116},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":549,"end":564},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":566,"end":568},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":795,"end":797},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1125,"end":1127},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1394,"end":1396},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":1497,"end":1499},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":1623,"end":1625},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T15","span":{"begin":1794,"end":1800},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T16","span":{"begin":1885,"end":1887},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0005011"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0005011"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0016063"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0005011"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0016063"},{"id":"A6","pred":"mondo_id","subj":"T5","obj":"0005011"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0016063"},{"id":"A8","pred":"mondo_id","subj":"T7","obj":"0005011"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0016063"},{"id":"A10","pred":"mondo_id","subj":"T9","obj":"0005011"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"0016063"},{"id":"A12","pred":"mondo_id","subj":"T11","obj":"0005011"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"0016063"},{"id":"A14","pred":"mondo_id","subj":"T13","obj":"0005011"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"0008568"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"0016063"},{"id":"A17","pred":"mondo_id","subj":"T16","obj":"0005011"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T2","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T7","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T9","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T11","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T13","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T15","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T16","pred":"source","obj":"PMID_GLOBAL"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#eceb93","default":true},{"id":"DisGeNET5_gene_disease","color":"#d193ec"},{"id":"sonoma2","color":"#93ecb7"},{"id":"PMID_GLOBAL","color":"#ec9d93"}]}]}}