A network-based analysis of systemic inflammation in humans
A network-based analysis of systemic inflammation in humans
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DOI：
10.1038/nature03985
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发表时间：
2005-10-13
期刊：
影响因子：
64.8
通讯作者：
Lowry, SF
中科院分区：
文献类型：
--
作者：
Calvano, SE;Xiao, WZ;Lowry, SF
寡核苷酸和互补 DNA 微阵列可用于对组织学相似的肿瘤进行细分、监测疾病进展并制定个体化治疗方案(1-5)。然而，从人类疾病的高通量基因组研究中提取新的生物学见解是一项挑战，因为从大量实验数据中识别和评估相关生物过程存在困难。在这里，我们提出了一种结构化网络知识库方法，用于在蛋白质、小分子和表型之间已知的功能相互关系的背景下分析全基因组转录反应。该方法用于分析接受炎症刺激（细菌内毒素）的人类受试者血液白细胞基因表达模式的变化。我们探索已知的全基因组相互作用网络，以识别响应这种刺激而受到干扰的重要功能模块。我们的分析表明，人类血液白细胞对急性全身炎症的反应包括白细胞生物能的短暂失调和转化机制的调节。这些发现提供了对全球白细胞活动调节的深入了解，因为它们与先天免疫系统耐受性和人类感染易感性增加有关。
Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens(1-5). However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus ( bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.