A Systematic Strategy for Screening and Application of Specific Biomarkers in Hepatotoxicity Using Metabolomics Combined With ROC Curves and SVMs

Toxicological Sciences : an Official Journal of the Society of Toxicology
Yubo LiYanjun Zhang

Abstract

Current studies that evaluate toxicity based on metabolomics have primarily focused on the screening of biomarkers while largely neglecting further verification and biomarker applications. For this reason, we used drug-induced hepatotoxicity as an example to establish a systematic strategy for screening specific biomarkers and applied these biomarkers to evaluate whether the drugs have potential hepatotoxicity toxicity. Carbon tetrachloride (5 ml/kg), acetaminophen (1500 mg/kg), and atorvastatin (5 mg/kg) are established as rat hepatotoxicity models. Fifteen common biomarkers were screened by multivariate statistical analysis and integration analysis-based metabolomics data. The receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the biomarkers. We obtained 10 specific biomarker candidates with an area under the curve greater than 0.7. Then, a support vector machine model was established by extracting specific biomarker candidate data from the hepatotoxic drugs and nonhepatotoxic drugs; the accuracy of the model was 94.90% (92.86% sensitivity and 92.59% specificity) and the results demonstrated that those ten biomarkers are specific. 6 drugs were used to predict the hepatotoxicity by ...Continue Reading

References

Apr 1, 1997·Journal of Nutritional Science and Vitaminology·Y EgashiraH Sanada
Jul 18, 2002·Nature Reviews. Drug Discovery·Jeremy K NicholsonElaine Holmes
Oct 15, 2005·Analytical Chemistry·Age K SmildeRenger H Jellema
Nov 7, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Xin LuGuowang Xu
Feb 20, 2008·BMC Bioinformatics·Alvaro J González, Li Liao
Feb 23, 2008·Toxicology·Josef OzerShelli Schomaker
Sep 5, 2008·Analytical Chemistry·Sankar MahadevanCarolyn M Slupsky
Oct 25, 2008·Nature·Jeremy K Nicholson, John C Lindon
Nov 18, 2008·Journal of Lipid Research·John E Burke, Edward A Dennis
Mar 25, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity·Xavier RoussetAlan T Remaley
Jul 7, 2011·Electrophoresis·Cristina Legido-QuigleyElaine Holmes
Sep 17, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Toufan ParmanCarol E Green
Oct 25, 2011·Molecular Aspects of Medicine·Cesare IndiveriFerdinando Palmieri
Dec 14, 2011·The Journal of Nutrition·Cynthia StretchVickie E Baracos
Jun 12, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Xiaohui LinGuowang Xu
Jul 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Leila Choucha SnouberEric Leclerc
Nov 2, 2012·Molecular & Cellular Proteomics : MCP·Christin ChristinPeter Horvatovich
Apr 2, 2013·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Takashi KobayashiMasaru Yoshida
Apr 2, 2013·Metabolomics : Official Journal of the Metabolomic Society·Jianguo XiaDavid S Wishart
Nov 10, 2013·Analytical Chemistry·Benjamin J BlaiseBernard Allaouchiche
Nov 8, 2014·Computational and Structural Biotechnology Journal·Jinchun SunRichard Beger

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Citations

Sep 7, 2016·Frontiers in Pharmacology·Mercedes Robles-DíazM Isabel Lucena
Dec 28, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yanyan XuYanjun Zhang
Jul 19, 2019·Journal of Breath Research·Kavitha SeerangaiyanEdwin G Winkel
Nov 30, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haonan ZhouYubo Li
Apr 19, 2021·Briefings in Bioinformatics·Jianbo FuFeng Zhu
May 13, 2021·Drug Design, Development and Therapy·Shanze LiYubo Li
Dec 10, 2016·Journal of Agricultural and Food Chemistry·Shuang YangChanghao Sun

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