“大数据”预测分析与三丁基锡暴露有关疾病
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摘要
通过毒理学"大数据",挖掘三丁基锡(TBT)潜在的生物影响信息,预测分析TBT暴露与人类相关疾病的关系.通过比较毒理组学数据库(CTD)搜集到488个和TBT具有相互作用的基因.基因相互作用网络图显示TP53拥有相关联基因最多,处于中心地位;其次是ESR1和FN1.CTD分析与TBT相关的疾病,发现前10类疾病分别是癌症、神经系统疾病、心血管疾病、泌尿生殖系统疾病(女)、消化系统疾病、代谢疾病、泌尿生殖系统疾病(男)、内分泌系统疾病、免疫系统疾病、呼吸道疾病.KEGG通路和DAVID基因功能注释分析,发现TBT不仅和代谢性疾病有较高的关联性,其相互作用基因在糖代谢途径上亦有较密集的基因功能注释.PASS的活性预测也发现TBT可能影响多种与糖代谢相关的酶生物活性.这提示TBT对糖代谢相关疾病的影响应引起人们的注意.
The potential influence information of tributyltin(TBT) was excavated to predict the relationship between TBT exposure and human-related diseases by using the "big data" of toxicology database. In comparative toxicogenomics database(CTD), 488 genes interacting with TBT were collected. Among the 488 genes, TP53 was the most associated genes, followed by ESR1 and FN1. Using CTD analysis, it was also found that cancer, nervous system diseases, cardiovascular diseases, urogenital disease(female), digestive system diseases, metabolic disease, urogenital disease(male), endocrine system diseases, immune system diseases andrespiratory tract disease were the top 10 diseases related to TBT exposure. Based KEGG pathway and DAVID gene function annotation analysis, metabolic diseases were more susceptible to be induced by TBT exposure; moreover, intensive genes interacting with TBT were annotated in the pathways of glucose metabolism. PASS prediction found that biological activities of many sugar-related enzymes could be affected by TBT exposure, which suggested that the impact of TBT on glucose metabolism should be of concern.
The potential influence information of tributyltin(TBT) was excavated to predict the relationship between TBT exposure and human-related diseases by using the "big data" of toxicology database. In comparative toxicogenomics database(CTD), 488 genes interacting with TBT were collected. Among the 488 genes, TP53 was the most associated genes, followed by ESR1 and FN1. Using CTD analysis, it was also found that cancer, nervous system diseases, cardiovascular diseases, urogenital disease(female), digestive system diseases, metabolic disease, urogenital disease(male), endocrine system diseases, immune system diseases andrespiratory tract disease were the top 10 diseases related to TBT exposure. Based KEGG pathway and DAVID gene function annotation analysis, metabolic diseases were more susceptible to be induced by TBT exposure; moreover, intensive genes interacting with TBT were annotated in the pathways of glucose metabolism. PASS prediction found that biological activities of many sugar-related enzymes could be affected by TBT exposure, which suggested that the impact of TBT on glucose metabolism should be of concern.
引文
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[31]Grün F,Blumberg B.Environmental obesogens:organotins and endocrinedisruption via nuclear receptor signaling[J].Endocrinology,2006,147:S50-S55.
[32]Zhang J,Zuo Z,He C,et al.Effect of tributyltin on testicular development in Sebastiscus marmoratus and the mechanism involved[J].Environmental Toxicology and Chemistry,2009,28:1528-1535.
[33]Zenz T,Eichhorst B R,Denzel T,et al.TP53mutation and survival in chronic lymphocytic leukemia[J].Journal of Clinical Oncology,2010,28(29):4473-4479.
[34]胥志祥,刘君,罗闹,等.DBP和BPA对MCF-7细胞的联合效应及机制[J].中国环境科学,2017,37(12):4771-4780.
[35]Sang H P,Yun I D,Sang U L,et al.Color image segmentation based on3-D clustering:morphological approach fn1[J].Pattern Recognition,1998,31(8):1061-1076.
[36]Lawrence S,Pellom S T Jr,Shanker A,et al.Tributyltin exposure alters cytokine levels in mouse serum[J].Journal of Immunotoxicology,2016,13(6):870-878.
[37]Zhang J,Sun P,Kong T,et al.Tributyltin promoted hepatic steatosis in zebrafish(Danio rerio)and the molecular pathogenesis involved[J].Aquatic Toxicology,2016,170:208-215.
[38]Papenfort K,Sun Y,Miyakoshi M,et al.Small RNA-mediated activation of sugar phosphatase m RNA regulates glucose homeostasis[J].Cell,2013,153(2):426-437.
[39]Nagy C,Einwallner E.Study of in vivo glucose metabolism in high-fat diet-fed mice using oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)[J].Journal of Visualized Experiments,2018,131:e56672
[2]Furdek M,Vah?i?M,S?an?ar J,et al.Organotin compounds in seawater and Mytilus galloprovincialis mussels along the Croatian Adriatic Coast[J].Marine Pollution Bulletin,2012,64(2):189-199.
[3]Kucuksezgin F,Aydin-Onen S,Gonul L T,et al.Assessment of organotin(butyltin species)contamination in marine biota from the Eastern Aegean Sea,Turkey[J].Marine Pollution Bulletin,2011,62:1984-1988.
[4]Kannan K,Takahashi S,Fujiwara N,et al.Organotin compounds,including butyltins and octyltins,in house dust from Albany,New York,USA[J].Archives of Environmental Contamination and Toxicology,2010,58:901-907.
[5]Airaksinen R,Rantakokko P,Turunen A W,et al.Organotin intake through fish consumption in Finland[J].Environmental Research,2010,110:544-547.
[6]Santos M M,Enes P,Reis-Henriques M A,et al.Organotin levels in seafood from Portuguese markets and the risk for consumers[J].Chemosphere,2009,75:661-666.
[7]Guerin T,Sirot V,Volatier J L,et al.Organotin levels in seafood and its implications for health risk in high-seafood consumers[J].Science of The Total Environment,2007,388:66-77.
[8]Lee C C,Wang T,Hsieh C Y,et al.Organotin contamination in fishes with different living patterns and its implications for human health risk in Taiwan[J].Environmental Pollution,2005,137:198-208.
[9]Zhou Q F,Jiang G B,Liu J Y.Small-scale survey on the contamination status of butyltin compounds in seafoods collected from seven Chinese cities[J].Journal of Agricultural and Food Chemistry,2001,49:4287-4291.
[10]李中阳,周群芳,江桂斌.我国部分城市市售海产品中丁基锡污染现状[J].中国环境科学,2003,23(2):144-147.
[11]赵孔祥,赵云峰,吴永宁.中国居民膳食有机锡污染水平和摄人量[J].中国预防医学杂志,2007,41(6):453-457.
[12]Rantakokko P,Turunen A,Verkasalo P K,et al.Blood levels of organotin compounds and their relation to fish consumption in Finland[J].Science of The Total Environment,2008,399:90-95.
[13]Nielsen J B.,Strand J.Butyltin compounds in human liver[J].Environmental Research,2002,88(2):129-133.
[14]王燕,陈永刚,葛郑增,等.TBT对大鼠肝脏ROS、抗氧化酶和解毒系统酶的影响[J].中国环境科学,2005,25(4):428-431.
[15]Dudimah F D,Griffey D,Wang X,et al.Activation of p44/42MAPK plays a role in the TBT-induced loss of human natural killer(NK)cell function[J].Cell Biology and Toxicology,2010,26(5):435-444.
[16]Ishihara Y,Kawami T,Ishida A,et al.Tributyltin induces oxidative stress and neuronal injury by inhibiting glutathione S-transferase in rat organotypic hippocampal slice cultures[J].Neurochemistry International,2012,60(8):782-790.
[17]Nakatsu Y,Kotake Y,Takai N,et al.Involvement of autophagy via mammalian target of rapamycin(m TOR)inhibition in tributyltininduced neuronal cell death[J].The Journal of Toxicological Sciences,2010,35(2):245-251.
[18]Zuo Z,Chen S,Wu T,et al.Tributyltin causes obesity and hepatic steatosis in male mice[J].Environmental Toxicology,2011,26(1):79-85.
[19]Grondin M,Marion M,Denizeau F,et al.Tributyltin induces apoptotic signaling in hepatocytes through pathways involving the endoplasmic reticulum and mitochondria[J].Toxicology and Applied Pharmacology,2007,222(1):57-68.
[20]Ye H,Ng H W,Sakkiah S,et al.Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors[J].International Journal of Environmental Research and Public Health,2016,13(4):373.
[21]Davis A P,Wiegers T C,King B L,et al.Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database[J].PLOS ONE,2016,11(5):e0155530.
[22]Hu B,Gifford E,Wang H,et al.Analysis of the Tox Cast ChemicalAssay Space Using the Comparative Toxicogenomics Database[J].Chemical Research in Toxicology,2015,28(11):2210-2223.
[23]Cheng L,Jiang Y,Wang Z,et al.Dis Sim:an online system for exploring significant similar diseases and exhibiting potential therapeutic drugs[J].Scientific Reports,2016,6:30024.
[24]Davis A P,Grondin C J,Johnson R J,et al.The Comparative Toxicogenomics Database:update 2017[J].Nucleic Acids Research,2017,45(D1):D972-D978.
[25]Boyle E I,Weng S,Gollub J,et al.GO::Term Finder—open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes[J].Bioinformatics,2004,20(18):3710-3715.
[26]Kanehisa M,Furumichi M,Tanabe M,et al.KEGG:new perspectives on genomes,pathways,diseases and drugs[J].Nucleic Acids Research,2017,45(D1):D353-D361.
[27]Huang D W,Sherman B T,Lempicki R A.Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J].Nature Protocols,2009,4(1):44-57.
[28]Huang D W,Sherman B T,Lempicki R A.Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists[J].Nucleic Acids Research,2009,37(1):1-13.
[29]Filimonov D A,Lagunin A A,Gloriozova T A,et al.Prediction of the biological activity spectra of organic compounds using the PASS online web resource[J].Chemistry of Heterocyclic Compounds,2014,50(3):444-457.
[30]Shao X,Wang M,Wei X,et al.Peroxisome proliferator-activated receptor-γ:master regulator of adipogenesis and obesity[J].Current Stem Cell Research&Therapy,2016,11(3):282-289.
[31]Grün F,Blumberg B.Environmental obesogens:organotins and endocrinedisruption via nuclear receptor signaling[J].Endocrinology,2006,147:S50-S55.
[32]Zhang J,Zuo Z,He C,et al.Effect of tributyltin on testicular development in Sebastiscus marmoratus and the mechanism involved[J].Environmental Toxicology and Chemistry,2009,28:1528-1535.
[33]Zenz T,Eichhorst B R,Denzel T,et al.TP53mutation and survival in chronic lymphocytic leukemia[J].Journal of Clinical Oncology,2010,28(29):4473-4479.
[34]胥志祥,刘君,罗闹,等.DBP和BPA对MCF-7细胞的联合效应及机制[J].中国环境科学,2017,37(12):4771-4780.
[35]Sang H P,Yun I D,Sang U L,et al.Color image segmentation based on3-D clustering:morphological approach fn1[J].Pattern Recognition,1998,31(8):1061-1076.
[36]Lawrence S,Pellom S T Jr,Shanker A,et al.Tributyltin exposure alters cytokine levels in mouse serum[J].Journal of Immunotoxicology,2016,13(6):870-878.
[37]Zhang J,Sun P,Kong T,et al.Tributyltin promoted hepatic steatosis in zebrafish(Danio rerio)and the molecular pathogenesis involved[J].Aquatic Toxicology,2016,170:208-215.
[38]Papenfort K,Sun Y,Miyakoshi M,et al.Small RNA-mediated activation of sugar phosphatase m RNA regulates glucose homeostasis[J].Cell,2013,153(2):426-437.
[39]Nagy C,Einwallner E.Study of in vivo glucose metabolism in high-fat diet-fed mice using oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)[J].Journal of Visualized Experiments,2018,131:e56672