Computationally identifying novel NF-κB-regulated immune genes in the human genome
Computationally identifying novel NF-κB-regulated immune genes in the human genome
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DOI：
10.1101/gr.911803
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发表时间：
2003-04-01
期刊：
影响因子：
7
通讯作者：
States, DJ
中科院分区：
文献类型：
--
作者：
Liu, RX;McEachin, RC;States, DJ
在人类基因组中识别新的NF-κ B调节的免疫基因对于我们理解免疫机制和免疫疾病非常重要。我们将逻辑回归模型拟合到62个已知NF-κ B调节的免疫基因的启动子中，以发现具有已知免疫功能的基因的启动子中转录因子结合的模式。使用这些模式，我们扫描了其他基因的启动子，以找到与模式匹配的基因，选择那些在小鼠或苍蝇中保守的NF-κ B结合位点，然后根据表达数据确认它们为NF-κ B调节的免疫基因。在6440个先前鉴定的人类基因组启动子中，我们发现了28个预测的免疫基因启动子，其中19个调节具有已知功能的基因，使我们能够计算该方法的特异性为93%-100%。当搜索62个已知的免疫基因启动子时，我们计算出42%的灵敏度。我们发现了9个新的NF-κ B调节的免疫基因，这些基因与现有的SAGE数据一致。我们预测基因功能的方法，基于转录因子结合的特征模式，进化保守性和表达研究，将适用于寻找具有其他功能的基因。
Identifying novel NF-kappaB-regulated immune genes in the human genome is important to our understanding of immune mechanisms and immune diseases. We fit logistic regression models to the promoters of 62 known NF-kappaB-regulated immune genes, to find patterns of transcription factor binding in the promoters of genes with known immune function. Using these patterns, we scanned the promoters of additional genes to find matches to the patterns, selected those with NF-kappaB binding sites conserved in the mouse or fly, and then confirmed them as NF-kappaB-regulated immune genes based on expression data. Among 6440 previously identified promoters in the human genome, we found 28 predicted immune gene promoters, 19 of which regulate genes with known function, allowing us to calculate specificity of 93%-100% for the method. We calculated sensitivity of 42% when searching the 62 known immune gene promoters. We found nine novel NF-kappaB-regulated immune genes which are consistent with available SAGE data. Our method of predicting gene function, based on characteristic patterns of transcription factor binding, evolutionary conservation, and expression studies, would be applicable to finding genes with other functions.