Gene expression phenotypes of atherosclerosis

Gene expression phenotypes of atherosclerosis
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DOI:
10.1161/01.atv.0000141358.65242.1f
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发表时间:
2004-10-01
影响因子:
8.7
通讯作者:
Goldschmidt-Clermont, PJ
Goldschmidt-Clermont, PJ
中科院分区:
医学1区
文献类型:
--
作者:
Seo, D;Wang, T;Goldschmidt-Clermont, PJ

文献摘要

被引文献

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目标 - 通过开发个体化的动脉粥样硬化诊断和治疗策略来实现个性化医疗的承诺将取决于对导致疾病易感性和进展的基因和基因变异的详细了解。为此,我们小组通过识别与人类目标组织中的疾病状态高度相关的基因表达模式,开发了一种与复杂疾病的多基因概念一致的无偏见方法。方法和结果 - 我们分析了具有不同程度动脉粥样硬化的人类主动脉样本集合,以确定预测疾病状态或潜在易感性的基因表达模式。我们发现与这些疾病测量中的每一种相关的基因表达特征,并且在每次分析中预测新样本的分类时可靠且稳健,>93%。提供预测能力的基因包括许多先前怀疑在动脉粥样硬化中发挥作用的基因以及先前与动脉粥样硬化没有关联的其他基因。结论 - 因此,我们报告了一种新方法,用于生成疾病的分子表型,然后识别其辨别能力强烈暗示其在人类动脉粥样硬化中的潜在作用的基因。
Objective - Fulfilling the promise of personalized medicine by developing individualized diagnostic and therapeutic strategies for atherosclerosis will depend on a detailed understanding of the genes and gene variants that contribute to disease susceptibility and progression. To that end, our group has developed a nonbiased approach congruent with the multigenic concept of complex diseases by identifying gene expression patterns highly associated with disease states in human target tissues.Methods and Results - We have analyzed a collection of human aorta samples with varying degrees of atherosclerosis to identify gene expression patterns that predict a disease state or potential susceptibility. We find gene expression signatures that relate to each of these disease measures and are reliable and robust in predicting the classification for new samples with >93% in each analysis. The genes that provide the predictive power include many previously suspected to play a role in atherosclerosis and additional genes without prior association with atherosclerosis.Conclusion - Hence, we are reporting a novel method for generating a molecular phenotype of disease and then identifying genes whose discriminatory capability strongly implicates their potential roles in human atherosclerosis.