Natsoulis Georges, Pearson Cecelia I, Gollub Jeremy, P Eynon Barrett, Ferng Joe, Nair Ramesh, Idury Radha, Lee May D, Fielden Mark R, Brennan Richard J, Roter Alan H, Jarnagin Kurt
Iconix Biosciences now Entelos, Foster City, CA, USA.
Mol Syst Biol. 2008;4:175. doi: 10.1038/msb.2008.9. Epub 2008 Mar 25.
We have used a supervised classification approach to systematically mine a large microarray database derived from livers of compound-treated rats. Thirty-four distinct signatures (classifiers) for pharmacological and toxicological end points can be identified. Just 200 genes are sufficient to classify these end points. Signatures were enriched in xenobiotic and immune response genes and contain un-annotated genes, indicating that not all key genes in the liver xenobiotic responses have been characterized. Many signatures with equal classification capabilities but with no gene in common can be derived for the same phenotypic end point. The analysis of the union of all genes present in these signatures can reveal the underlying biology of that end point as illustrated here using liver fibrosis signatures. Our approach using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development.
我们采用了一种监督分类方法，系统地挖掘了一个源自经化合物处理大鼠肝脏的大型微阵列数据库。可以识别出34个用于药理学和毒理学终点的不同特征（分类器）。仅200个基因就足以对这些终点进行分类。特征在异生物质和免疫反应基因中富集，并且包含未注释的基因，这表明并非肝脏异生物质反应中的所有关键基因都已得到表征。对于相同的表型终点，可以得出许多具有相同分类能力但没有共同基因的特征。如在此使用肝纤维化特征所示，对这些特征中存在的所有基因的并集进行分析可以揭示该终点的潜在生物学机制。我们使用全基因组和多种化合物的方法能够全面了解大多数药理学和毒理学问题，并且适用于其他情况，如疾病和发育。
