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首页> 外文期刊>International Journal of Environmental Research and Public Health >Using Bioinformatic Approaches to Identify Pathways Targeted by Human Leukemogens
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Using Bioinformatic Approaches to Identify Pathways Targeted by Human Leukemogens

机译：使用生物信息化方法来识别人白血病靶向的途径

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We have applied bioinformatic approaches to identify pathways common to chemical leukemogens and to determine whether leukemogens could be distinguished from non-leukemogenic carcinogens. From all known and probable carcinogens classified by IARC and NTP, we identified 35 carcinogens that were associated with leukemia risk in human studies and 16 non-leukemogenic carcinogens. Using data on gene/protein targets available in the Comparative Toxicogenomics Database (CTD) for 29 of the leukemogens and 11 of the non-leukemogenic carcinogens, we analyzed for enrichment of all 250 human biochemical pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The top pathways targeted by the leukemogens included metabolism of xenobiotics by cytochrome P450, glutathione metabolism, neurotrophin signaling pathway, apoptosis, MAPK signaling, Toll-like receptor signaling and various cancer pathways. The 29 leukemogens formed 18 distinct clusters comprising 1 to 3 chemicals that did not correlate with known mechanism of action or with structural similarity as determined by 2D Tanimoto coefficients in the PubChem database. Unsupervised clustering and one-class support vector machines, based on the pathway data, were unable to distinguish the 29 leukemogens from 11 non-leukemogenic known and probable IARC carcinogens. However, using two-class random forests to estimate leukemogen and non-leukemogen patterns, we estimated a 76% chance of distinguishing a random leukemogen/non-leukemogen pair from each other.
机译：我们已经应用生物信息化方法来鉴定化学白血病常见的途径，并确定白血病是否可以与非白血病致癌物质区分开。来自由IARC和NTP分类的所有已知和可能的致癌物，我们鉴定了35种与人类研究中的白血病风险相关的致癌物和16种非白血病致癌物。使用对比较有毒癌症组织（CTD）中可用的基因/蛋白质靶标的数据（CTD）29种白血病和11种非白血病致癌物质，我们分析了在基因和基因组的京都百科全书中富集所有250例人类生化途径（Kegg ）数据库。白血病靶向的顶部途径包括细胞色素P450，谷胱甘肽代谢，神经营养素信号传导途径，细胞凋亡，MAPK信号传导，收费的受体信号和各种癌症途径的代谢。形成18个不同的簇，其包含1至3种化学物质，其与已知的作用机制或具有由Pubchem数据库中的2D Tanimoto系数确定的结构相似性不相关。根据途径数据，无监督的聚类和单级支持向量机无法区分来自11个非白血病的29只白血病和可能的IARC致癌物质。然而，利用两类随机森林来估计白血病和非白血病模式，我们估计了76％的几率区分随机性白血病/非白血病彼此的几率。

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