Bhattacharya Soumyaroop, Mariani Thomas J
Division of Neonatology and Center for Pediatric Biomedical Research, University of Rochester, Rochester, NY 14642, USA.
Biochem Soc Trans. 2009 Aug;37(Pt 4):855-62. doi: 10.1042/BST0370855.
High-throughput, genome-wide analytical technologies are now commonly used in all fields of medical research. The most commonly applied of these technologies, gene expression microarrays, have been shown to be both accurate and precise when properly implemented. For over a decade, microarrays have provided novel insight into many complex human diseases. Microarray-based discovery can be classified into three components, biomarker detection, disease (sub)classification and identification of causal mechanism, in order of accomplishment. Within the respiratory system, the application of microarrays has achieved significant success in all components, particularly with respect to lung cancer. Numerous studies over the last half-decade have applied this technology to the characterization of non-malignant respiratory diseases, animal models of respiratory disease and normal developmental processes. Studies of obstructive lung diseases by many groups, including our own, have yielded not only disease biomarkers, but also some novel putative pathogenic mechanisms. We have successfully used an integrative genomics approach, combining microarray analysis with human genetics, to identify susceptibility genes for COPD (chronic obstructive pulmonary disease). Interestingly, we find that the assessment of quantitative phenotypic variables enhances gene discovery. Our studies contribute to the identification of obstructive lung disease biomarkers, provide data associated with disease phenotypes and support the use of an integrated approach to move beyond marker identification to mechanism discovery.
高通量、全基因组分析技术目前在医学研究的各个领域普遍使用。这些技术中应用最广泛的基因表达微阵列，在正确实施时已被证明既准确又精确。十多年来，微阵列对许多复杂的人类疾病提供了新的见解。基于微阵列的发现可按完成顺序分为三个部分，即生物标志物检测、疾病（亚）分类和因果机制识别。在呼吸系统中，微阵列的应用在所有这些方面都取得了显著成功，尤其是在肺癌方面。在过去五年中，众多研究将该技术应用于非恶性呼吸系统疾病、呼吸系统疾病动物模型以及正常发育过程的特征描述。包括我们自己在内的许多研究团队对阻塞性肺疾病的研究不仅产生了疾病生物标志物，还发现了一些新的假定致病机制。我们成功地运用了整合基因组学方法，将微阵列分析与人类遗传学相结合，以确定慢性阻塞性肺疾病（COPD）的易感基因。有趣的是，我们发现对定量表型变量的评估增强了基因发现。我们的研究有助于阻塞性肺疾病生物标志物的识别，提供与疾病表型相关的数据，并支持使用综合方法从标志物识别转向机制发现。
