Statistical Methods for Analysis of Array CGH Data

描述（由申请人提供）：项目摘要：本提案的主要目标是在个体水平的“信号处理”和群体水平的检测模式上开发用于阵列比较基因组杂交（aCGH）数据的统计分析的计算易处理方法。在个体水平上的分析，我们的目标是通过同时分析多个染色体和杂交，利用共同共享的功能，同时考虑染色体内和染色体之间以及杂交之间的变异性，以改善目前可用的方法。在人群水平上，我们将开发新的方法来定位基因组不稳定性的共同区域，并使用临床终点（如生存率）对患者进行聚类。这些方法的动机，并将被应用于，aCGH数据集从胶质瘤研究和脑膜瘤研究。相关性：恶性胶质瘤是最常见的原发性人类脑肿瘤。然而，在他们的病理分类的问题，复杂的病人管理，并引发了相当大的兴趣，分子诊断方法。我们的小组目前正在开发aCGH的方法，我们假设，可以提供一个敏感的，具体的，具有成本效益和快速的方法来评估人类恶性胶质瘤相关的遗传变化。脑膜瘤是一种常见的颅内肿瘤，常见于2型神经纤维瘤病（NF2）患者，也偶尔发生在没有生殖系NF2突变的个体中。有必要寻找可能在这些散发性脑膜瘤的发生和发展中起作用的遗传机制。此外，aCGH分析可能有助于家族性多发性脑膜瘤的鉴别诊断。阵列CGH有望揭示肿瘤中的小的不平衡染色体事件，并可以提供有关不平衡染色体片段（ICS）边界的特定信息。要对这些重要数据进行有效和有效的分析，就需要健全的统计方法。

DESCRIPTION (provided by applicant): Project Summary: The primary goal of this proposal is to develop computationally tractable methods of statistical analysis for array comparative genomic hybridization (aCGH) data at both the individual level of "signal processing" and the population level of detecting patterns. At the individual level of analysis, we aim to improve upon currently available methods through a simultaneous analysis of multiple chromosomes and hybridizations that exploits features that are shared in common, while accounting for variability within and between chromosomes and between hybridizations. At the population-level, we will develop novel methods for locating common regions of genomic instability and for clustering patients using clinical endpoints, such as survival. These methods are motivated by, and will be applied to, aCGH data sets from glioma studies and meningioma studies. Relevance: Malignant gliomas are the most common primary human brain tumors. Problems in their pathological classification, however, complicate patient management and have sparked considerable interest in molecular diagnostic approaches. Our group is currently developing methods for aCGH that, we hypothesize, can provide a sensitive, specific, cost-effective and rapid method to assess human malignant gliomas for relevant genetic changes. Meningioma, a common intracranial tumor found frequently in patients with neurofibromatosis type 2 (NF2), also occurs sporadically in individuals without germline NF2 mutations. It is necessary to seek genetic mechanisms that may operate in the initiation and progression of these sporadic meningiomas. In addition, aCGH profiling will likely be useful for differential diagnosis of familial multiple meningioma. Array CGH holds promise for uncovering small imbalanced chromosomal events in tumors and can provide specific information about the boundaries of the imbalanced chromosome segments (ICS). Sound statistical methods are required for efficient and valid analyses of these important data.