{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:59:51Z","timestamp":1791583191376,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T00:00:00Z","timestamp":1410998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"the Korean National Research Foundation","doi-asserted-by":"crossref","award":["2012M3A9D1054476, 2012R1A5A2047939"],"award-info":[{"award-number":["2012M3A9D1054476, 2012R1A5A2047939"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Drug\u2010induced liver injury (DILI) is a major safety concern during drug development and remains one of the main reasons for withdrawal of drugs from the market. Although it is crucial to develop methods that will detect potential hepatotoxicity of drug candidates as early and as quickly as possible, there is still a lack of sensitive and specific biomarkers for DILI that consequently leads to a scarcity of reliable hepatotoxic data. Hence, in this study, we assessed characteristic molecular signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine and chlorpromazine) that are known to cause DILI in humans. Unsupervised hierarchical clustering analysis of transcriptome changes induced by DILI\u2010causing drugs resulted in three different subclusters on dendrogram, i.e., hepatocellular, cholestatic and mixed type of DILI at early time points (2\u2009days), and multiclassification analysis suggested 31 genes as discernible markers for each DILI pattern. Further analysis for characteristic molecular signature of each DILI pattern provided a molecular basis for different modes of DILI action. A proteomics study of the same rat livers was used to confirm the results, and the two sets of data showed 60 matching classifiers. In conclusion, the data of different DILI\u2010causing drug treatments from genomic analysis in a rat model suggest that DILI\u2010specific molecular signatures can discriminate different patterns of DILI at an early exposure time point, and that they provide useful information for mechanistic studies that may lead to a better understanding of the molecular basis of DILI. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3062","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T04:29:36Z","timestamp":1411014576000},"page":"152-164","source":"Crossref","is-referenced-by-count":14,"title":["Characteristic molecular and proteomic signatures of drug\u2010induced liver injury in a rat model"],"prefix":"10.1002","volume":"35","author":[{"given":"Jung Woo","family":"Eun","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jin","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Chan","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Doo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Young","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jueng Soo","family":"You","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine Konkuk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Joo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoguen","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Min","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Kidney System, College of Oriental Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Sang","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Woo","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Functional RNomics Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Cancer Evolution Research Center, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250902927386"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","unstructured":"BaeCH KimDS JunYL KwonS ParkHJ HahmDH LeeH KimST.2013.Proteomic analysis of the effect of acupuncture on the suppression of kainic Acid\u2010induced neuronal destruction in mouse hippocampus. Evidence\u2010based complementary and alternative medicine: eCAM2013:436315. DOI:10.1155\/2013\/436315.","DOI":"10.1155\/2013\/436315"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.2.460"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.05.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900003"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1A055"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs222"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080106"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/es302480v"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.11.001"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1750"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(04)03166-6"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1118"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052270"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90470-4"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/15.2.101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp683"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.242"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230590888306"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200600207"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr130"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3062","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:33:58Z","timestamp":1760524438000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,18]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1002\/jat.3062"],"URL":"https:\/\/doi.org\/10.1002\/jat.3062","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,18]]}}}