PubMed:26586530 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/26586530","sourcedb":"PubMed","sourceid":"26586530","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/26586530","text":"Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia.\nProprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (-38.5%; P=0.038) and had a 71% decrease (P\u003c0.001) of low-density lipoprotein (LDL) uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A) displayed a strong decrease in PCSK9 secretion (-89.7%; P\u003c0.001) and had a 106% increase (P=0.0104) of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR) and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P\u003c0.01), in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5). In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function.","tracks":[{"project":"DisGeNET5_variant_disease","denotations":[{"id":"26586530-7#284#289#geners369067856","span":{"begin":1276,"end":1281},"obj":"geners369067856"},{"id":"26586530-7#290#295#geners775988212","span":{"begin":1282,"end":1287},"obj":"geners775988212"},{"id":"26586530-7#76#79#diseaseC1332347","span":{"begin":1068,"end":1071},"obj":"diseaseC1332347"},{"id":"26586530-7#81#90#diseaseC1332347","span":{"begin":1073,"end":1082},"obj":"diseaseC1332347"},{"id":"26586530-7#274#278#diseaseC1862596","span":{"begin":1266,"end":1270},"obj":"diseaseC1862596"},{"id":"26586530-7#76#79#diseaseC1332347","span":{"begin":1068,"end":1071},"obj":"diseaseC1332347"},{"id":"26586530-7#81#90#diseaseC1332347","span":{"begin":1073,"end":1082},"obj":"diseaseC1332347"},{"id":"26586530-7#274#278#diseaseC1862596","span":{"begin":1266,"end":1270},"obj":"diseaseC1862596"},{"id":"26586530-9#249#254#geners752942769","span":{"begin":1820,"end":1825},"obj":"geners752942769"},{"id":"26586530-9#249#254#geners762588484","span":{"begin":1820,"end":1825},"obj":"geners762588484"},{"id":"26586530-9#249#254#geners28942111","span":{"begin":1820,"end":1825},"obj":"geners28942111"},{"id":"26586530-9#105#114#diseaseC1332347","span":{"begin":1678,"end":1687},"obj":"diseaseC1332347"}],"relations":[{"id":"284#289#geners36906785676#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"284#289#geners36906785681#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"284#289#geners369067856274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"284#289#geners36906785676#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"284#289#geners36906785681#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"284#289#geners369067856274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#284#289#geners369067856","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"290#295#geners77598821276#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"290#295#geners77598821281#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"290#295#geners775988212274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"290#295#geners77598821276#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"290#295#geners77598821281#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"290#295#geners775988212274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#290#295#geners775988212","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"249#254#geners752942769105#114#diseaseC1332347","pred":"associated_with","subj":"26586530-9#249#254#geners752942769","obj":"26586530-9#105#114#diseaseC1332347"},{"id":"249#254#geners762588484105#114#diseaseC1332347","pred":"associated_with","subj":"26586530-9#249#254#geners762588484","obj":"26586530-9#105#114#diseaseC1332347"},{"id":"249#254#geners28942111105#114#diseaseC1332347","pred":"associated_with","subj":"26586530-9#249#254#geners28942111","obj":"26586530-9#105#114#diseaseC1332347"}],"attributes":[{"subj":"26586530-7#284#289#geners369067856","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#290#295#geners775988212","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#76#79#diseaseC1332347","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#81#90#diseaseC1332347","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#274#278#diseaseC1862596","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#76#79#diseaseC1332347","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#81#90#diseaseC1332347","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-7#274#278#diseaseC1862596","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-9#249#254#geners752942769","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-9#249#254#geners762588484","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-9#249#254#geners28942111","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"26586530-9#105#114#diseaseC1332347","pred":"source","obj":"DisGeNET5_variant_disease"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"26586530-0#78#83#gene255738","span":{"begin":78,"end":83},"obj":"gene255738"},{"id":"26586530-0#93#132#diseaseC0745103","span":{"begin":93,"end":132},"obj":"diseaseC0745103"},{"id":"26586530-2#8#13#gene255738","span":{"begin":248,"end":253},"obj":"gene255738"},{"id":"26586530-2#127#142#diseaseC0003850","span":{"begin":367,"end":382},"obj":"diseaseC0003850"},{"id":"26586530-2#127#142#diseaseC0004153","span":{"begin":367,"end":382},"obj":"diseaseC0004153"},{"id":"26586530-7#106#111#gene255738","span":{"begin":1098,"end":1103},"obj":"gene255738"},{"id":"26586530-7#328#333#gene255738","span":{"begin":1320,"end":1325},"obj":"gene255738"},{"id":"26586530-7#76#79#diseaseC1332347","span":{"begin":1068,"end":1071},"obj":"diseaseC1332347"},{"id":"26586530-7#81#90#diseaseC1332347","span":{"begin":1073,"end":1082},"obj":"diseaseC1332347"},{"id":"26586530-7#274#278#diseaseC1862596","span":{"begin":1266,"end":1270},"obj":"diseaseC1862596"},{"id":"26586530-7#76#79#diseaseC1332347","span":{"begin":1068,"end":1071},"obj":"diseaseC1332347"},{"id":"26586530-7#81#90#diseaseC1332347","span":{"begin":1073,"end":1082},"obj":"diseaseC1332347"},{"id":"26586530-7#274#278#diseaseC1862596","span":{"begin":1266,"end":1270},"obj":"diseaseC1862596"}],"relations":[{"id":"78#83#gene25573893#132#diseaseC0745103","pred":"associated_with","subj":"26586530-0#78#83#gene255738","obj":"26586530-0#93#132#diseaseC0745103"},{"id":"8#13#gene255738127#142#diseaseC0003850","pred":"associated_with","subj":"26586530-2#8#13#gene255738","obj":"26586530-2#127#142#diseaseC0003850"},{"id":"8#13#gene255738127#142#diseaseC0004153","pred":"associated_with","subj":"26586530-2#8#13#gene255738","obj":"26586530-2#127#142#diseaseC0004153"},{"id":"106#111#gene25573876#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"106#111#gene25573881#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"106#111#gene255738274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"106#111#gene25573876#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"106#111#gene25573881#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"106#111#gene255738274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#106#111#gene255738","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"328#333#gene25573876#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"328#333#gene25573881#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"328#333#gene255738274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#274#278#diseaseC1862596"},{"id":"328#333#gene25573876#79#diseaseC1332347","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#76#79#diseaseC1332347"},{"id":"328#333#gene25573881#90#diseaseC1332347","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#81#90#diseaseC1332347"},{"id":"328#333#gene255738274#278#diseaseC1862596","pred":"associated_with","subj":"26586530-7#328#333#gene255738","obj":"26586530-7#274#278#diseaseC1862596"}],"attributes":[{"subj":"26586530-0#78#83#gene255738","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-0#93#132#diseaseC0745103","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-2#8#13#gene255738","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-2#127#142#diseaseC0003850","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-2#127#142#diseaseC0004153","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#106#111#gene255738","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#328#333#gene255738","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#76#79#diseaseC1332347","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#81#90#diseaseC1332347","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#274#278#diseaseC1862596","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#76#79#diseaseC1332347","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#81#90#diseaseC1332347","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"26586530-7#274#278#diseaseC1862596","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"kaiyin_test","denotations":[{"id":"T1","span":{"begin":248,"end":253},"obj":"Gene"},{"id":"T2","span":{"begin":254,"end":270},"obj":"PosReg"},{"id":"T3","span":{"begin":277,"end":286},"obj":"Var"},{"id":"T4","span":{"begin":307,"end":346},"obj":"Disease"},{"id":"T5","span":{"begin":357,"end":382},"obj":"Disease"},{"id":"T6","span":{"begin":384,"end":389},"obj":"Gene"},{"id":"T7","span":{"begin":390,"end":406},"obj":"NegReg"},{"id":"T8","span":{"begin":413,"end":422},"obj":"Var"},{"id":"T9","span":{"begin":423,"end":427},"obj":"PosReg"},{"id":"T10","span":{"begin":430,"end":454},"obj":"CPA"},{"id":"T11","span":{"begin":485,"end":517},"obj":"Disease"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T3"},{"id":"R2","pred":"CauseOf","subj":"T3","obj":"T2"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T2"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T2"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T8"},{"id":"R6","pred":"CauseOf","subj":"T8","obj":"T7"},{"id":"R7","pred":"ThemeOf","subj":"T11","obj":"T7"},{"id":"R8","pred":"CauseOf","subj":"T8","obj":"T9"},{"id":"R9","pred":"ThemeOf","subj":"T10","obj":"T9"}],"attributes":[{"subj":"T1","pred":"source","obj":"kaiyin_test"},{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"},{"subj":"T7","pred":"source","obj":"kaiyin_test"},{"subj":"T8","pred":"source","obj":"kaiyin_test"},{"subj":"T9","pred":"source","obj":"kaiyin_test"},{"subj":"T10","pred":"source","obj":"kaiyin_test"},{"subj":"T11","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T1","span":{"begin":248,"end":253},"obj":"Gene"},{"id":"T2","span":{"begin":254,"end":270},"obj":"PosReg"},{"id":"T3","span":{"begin":277,"end":286},"obj":"Var"},{"id":"T4","span":{"begin":307,"end":346},"obj":"Disease"},{"id":"T5","span":{"begin":357,"end":382},"obj":"Disease"},{"id":"T6","span":{"begin":384,"end":389},"obj":"Gene"},{"id":"T7","span":{"begin":390,"end":406},"obj":"NegReg"},{"id":"T8","span":{"begin":413,"end":422},"obj":"Var"},{"id":"T9","span":{"begin":423,"end":427},"obj":"PosReg"},{"id":"T10","span":{"begin":430,"end":454},"obj":"CPA"},{"id":"T11","span":{"begin":485,"end":517},"obj":"Disease"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T3"},{"id":"R2","pred":"CauseOf","subj":"T3","obj":"T2"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T2"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T2"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T8"},{"id":"R6","pred":"CauseOf","subj":"T8","obj":"T7"},{"id":"R7","pred":"ThemeOf","subj":"T11","obj":"T7"},{"id":"R8","pred":"CauseOf","subj":"T8","obj":"T9"},{"id":"R9","pred":"ThemeOf","subj":"T10","obj":"T9"}],"attributes":[{"subj":"T1","pred":"source","obj":"name_no"},{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"},{"subj":"T7","pred":"source","obj":"name_no"},{"subj":"T8","pred":"source","obj":"name_no"},{"subj":"T9","pred":"source","obj":"name_no"},{"subj":"T10","pred":"source","obj":"name_no"},{"subj":"T11","pred":"source","obj":"name_no"}]},{"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":78,"end":92},"obj":"GENE"},{"id":"T1","span":{"begin":93,"end":132},"obj":"DISEASE"},{"id":"T2","span":{"begin":134,"end":179},"obj":"GENE"},{"id":"T3","span":{"begin":181,"end":186},"obj":"GENE"},{"id":"T4","span":{"begin":215,"end":238},"obj":"MPA"},{"id":"T5","span":{"begin":248,"end":253},"obj":"GENE"},{"id":"T6","span":{"begin":254,"end":270},"obj":"POSREG"},{"id":"T7","span":{"begin":272,"end":275},"obj":"POSREG"},{"id":"T8","span":{"begin":277,"end":286},"obj":"VAR"},{"id":"T9","span":{"begin":291,"end":301},"obj":"REG"},{"id":"T10","span":{"begin":307,"end":346},"obj":"DISEASE"},{"id":"T11","span":{"begin":348,"end":351},"obj":"DISEASE"},{"id":"T12","span":{"begin":357,"end":382},"obj":"DISEASE"},{"id":"T13","span":{"begin":384,"end":389},"obj":"GENE"},{"id":"T14","span":{"begin":390,"end":406},"obj":"NEGREG"},{"id":"T15","span":{"begin":408,"end":411},"obj":"NEGREG"},{"id":"T16","span":{"begin":413,"end":422},"obj":"VAR"},{"id":"T17","span":{"begin":430,"end":447},"obj":"CPA"},{"id":"T18","span":{"begin":448,"end":454},"obj":"CPA"},{"id":"T19","span":{"begin":477,"end":481},"obj":"REG"},{"id":"T20","span":{"begin":482,"end":484},"obj":"REG"},{"id":"T21","span":{"begin":485,"end":517},"obj":"DISEASE"},{"id":"T22","span":{"begin":519,"end":523},"obj":"DISEASE"},{"id":"T23","span":{"begin":631,"end":636},"obj":"GENE"},{"id":"T24","span":{"begin":637,"end":645},"obj":"VAR"},{"id":"T25","span":{"begin":776,"end":790},"obj":"GENE"},{"id":"T26","span":{"begin":791,"end":794},"obj":"DISEASE"},{"id":"T27","span":{"begin":799,"end":803},"obj":"DISEASE"},{"id":"T28","span":{"begin":1068,"end":1071},"obj":"DISEASE"},{"id":"T29","span":{"begin":1093,"end":1097},"obj":"NEGREG"},{"id":"T30","span":{"begin":1098,"end":1103},"obj":"GENE"},{"id":"T31","span":{"begin":1149,"end":1157},"obj":"NEGREG"},{"id":"T32","span":{"begin":1266,"end":1270},"obj":"DISEASE"},{"id":"T33","span":{"begin":1269,"end":1273},"obj":"DISEASE"},{"id":"T34","span":{"begin":1308,"end":1316},"obj":"NEGREG"},{"id":"T35","span":{"begin":1323,"end":1328},"obj":"GENE"},{"id":"T36","span":{"begin":1326,"end":1335},"obj":"MPA"},{"id":"T37","span":{"begin":1369,"end":1377},"obj":"POSREG"},{"id":"T38","span":{"begin":1440,"end":1448},"obj":"POSREG"},{"id":"T39","span":{"begin":1449,"end":1452},"obj":"GENE"},{"id":"T40","span":{"begin":1455,"end":1467},"obj":"GENE"},{"id":"T41","span":{"begin":1463,"end":1467},"obj":"GENE"},{"id":"T42","span":{"begin":1469,"end":1473},"obj":"GENE"},{"id":"T43","span":{"begin":1473,"end":1478},"obj":"GENE"},{"id":"T44","span":{"begin":1479,"end":1484},"obj":"GENE"},{"id":"T45","span":{"begin":1489,"end":1499},"obj":"MPA"},{"id":"T46","span":{"begin":1518,"end":1527},"obj":"MPA"},{"id":"T47","span":{"begin":1518,"end":1523},"obj":"GENE"},{"id":"T48","span":{"begin":1634,"end":1642},"obj":"POSREG"},{"id":"T49","span":{"begin":1646,"end":1656},"obj":"MPA"},{"id":"T50","span":{"begin":1820,"end":1825},"obj":"VAR"},{"id":"T51","span":{"begin":2065,"end":2070},"obj":"GENE"},{"id":"T52","span":{"begin":2071,"end":2080},"obj":"VAR"},{"id":"T53","span":{"begin":2076,"end":2081},"obj":"GENE"}],"relations":[{"id":"R0","pred":"ThemeOf","subj":"T5","obj":"T8"},{"id":"R1","pred":"CauseOf","subj":"T7","obj":"T6"},{"id":"R2","pred":"CauseOf","subj":"T6","obj":"T9"},{"id":"R3","pred":"CauseOf","subj":"T7","obj":"T9"},{"id":"R4","pred":"CauseOf","subj":"T8","obj":"T6"},{"id":"R5","pred":"CauseOf","subj":"T8","obj":"T7"},{"id":"R6","pred":"CauseOf","subj":"T8","obj":"T9"},{"id":"R7","pred":"CauseOf","subj":"T8","obj":"T14"},{"id":"R8","pred":"ThemeOf","subj":"T10","obj":"T6"},{"id":"R9","pred":"ThemeOf","subj":"T10","obj":"T7"},{"id":"R10","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R11","pred":"ThemeOf","subj":"T10","obj":"T14"},{"id":"R12","pred":"ThemeOf","subj":"T10","obj":"T15"},{"id":"R13","pred":"ThemeOf","subj":"T11","obj":"T6"},{"id":"R14","pred":"ThemeOf","subj":"T11","obj":"T7"},{"id":"R15","pred":"ThemeOf","subj":"T11","obj":"T9"},{"id":"R16","pred":"ThemeOf","subj":"T11","obj":"T14"},{"id":"R17","pred":"ThemeOf","subj":"T11","obj":"T15"},{"id":"R18","pred":"ThemeOf","subj":"T12","obj":"T6"},{"id":"R19","pred":"ThemeOf","subj":"T12","obj":"T7"},{"id":"R20","pred":"ThemeOf","subj":"T12","obj":"T9"},{"id":"R21","pred":"ThemeOf","subj":"T12","obj":"T14"},{"id":"R22","pred":"ThemeOf","subj":"T12","obj":"T15"},{"id":"R23","pred":"ThemeOf","subj":"T13","obj":"T16"},{"id":"R24","pred":"CauseOf","subj":"T15","obj":"T14"},{"id":"R25","pred":"ThemeOf","subj":"T17","obj":"T14"},{"id":"R26","pred":"CauseOf","subj":"T16","obj":"T6"},{"id":"R27","pred":"CauseOf","subj":"T16","obj":"T14"},{"id":"R28","pred":"CauseOf","subj":"T16","obj":"T15"},{"id":"R29","pred":"CauseOf","subj":"T16","obj":"T17"},{"id":"R30","pred":"CauseOf","subj":"T16","obj":"T19"},{"id":"R31","pred":"CauseOf","subj":"T16","obj":"T20"},{"id":"R32","pred":"ThemeOf","subj":"T17","obj":"T18"},{"id":"R33","pred":"ThemeOf","subj":"T21","obj":"T6"},{"id":"R34","pred":"ThemeOf","subj":"T21","obj":"T7"},{"id":"R35","pred":"ThemeOf","subj":"T21","obj":"T14"},{"id":"R36","pred":"ThemeOf","subj":"T21","obj":"T15"},{"id":"R37","pred":"ThemeOf","subj":"T21","obj":"T19"},{"id":"R38","pred":"ThemeOf","subj":"T21","obj":"T20"},{"id":"R39","pred":"ThemeOf","subj":"T22","obj":"T6"},{"id":"R40","pred":"ThemeOf","subj":"T22","obj":"T14"},{"id":"R41","pred":"ThemeOf","subj":"T22","obj":"T15"},{"id":"R42","pred":"ThemeOf","subj":"T22","obj":"T19"},{"id":"R43","pred":"ThemeOf","subj":"T22","obj":"T20"},{"id":"R44","pred":"ThemeOf","subj":"T23","obj":"T24"},{"id":"R45","pred":"ThemeOf","subj":"T28","obj":"T29"},{"id":"R46","pred":"ThemeOf","subj":"T28","obj":"T31"},{"id":"R47","pred":"ThemeOf","subj":"T32","obj":"T29"},{"id":"R48","pred":"ThemeOf","subj":"T32","obj":"T31"},{"id":"R49","pred":"ThemeOf","subj":"T32","obj":"T34"},{"id":"R50","pred":"CauseOf","subj":"T34","obj":"T37"},{"id":"R51","pred":"ThemeOf","subj":"T36","obj":"T34"},{"id":"R52","pred":"ThemeOf","subj":"T39","obj":"T38"},{"id":"R53","pred":"ThemeOf","subj":"T39","obj":"T45"},{"id":"R54","pred":"ThemeOf","subj":"T41","obj":"T38"},{"id":"R55","pred":"ThemeOf","subj":"T41","obj":"T45"},{"id":"R56","pred":"ThemeOf","subj":"T41","obj":"T46"},{"id":"R57","pred":"ThemeOf","subj":"T43","obj":"T38"},{"id":"R58","pred":"ThemeOf","subj":"T43","obj":"T45"},{"id":"R59","pred":"ThemeOf","subj":"T45","obj":"T38"},{"id":"R60","pred":"ThemeOf","subj":"T46","obj":"T45"},{"id":"R61","pred":"ThemeOf","subj":"T46","obj":"T38"},{"id":"R62","pred":"ThemeOf","subj":"T49","obj":"T48"},{"id":"R63","pred":"CauseOf","subj":"T50","obj":"T48"},{"id":"R64","pred":"ThemeOf","subj":"T51","obj":"T52"}],"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"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET5_variant_disease","color":"#a5ec93","default":true},{"id":"DisGeNET5_gene_disease","color":"#ec93bf"},{"id":"kaiyin_test","color":"#93d9ec"},{"id":"name_no","color":"#ece593"},{"id":"sonoma2","color":"#cb93ec"}]}]}}