Statistical Methods for the Genomic Analysis of Gene Expression Data

描述(申请人提供)：随着DNA测序、基因分型、基因注释、表达谱分析和其他高通量测量技术的进步，可行的科学问题的范围正在扩大，通常涉及从多种来源收集的数据。因此，从事统计学和生物学交界处工作的统计学家面临着为涉及多种类型数据的调查开发分析方法的挑战。1个重要的例子涉及确定基因表达的遗传基础的研究(eQTL定位研究)，其中相关数据包括表达测量、遗传图谱、关于转录本的共同调节的信息以及关于转录因子及其结合位点的信息。另一组研究涉及生理系统的遗传调节。这些数据包括时间进程表达测量、生理变量和转录本的共同调节信息。表达QTL定位和时间进程微阵列研究提供了对正常和疾病生物系统的基本洞察。它们被用来识别调控基因，洞察调控机制，并确定如何修改调控以促进或维持有益的反应。如果没有有效的统计方法，这些研究中的生物医学信息是不可能全面实现的。这项建议的目标是开发、评估和传播统计方法，以解决这两类研究中的问题。这一目标将通过三个具体目标来实现：开发确定绘图记录及其映射到的基因组位置的方法；将这些方法扩展到稀疏映射和密集映射的情况；以及开发确定表达和影响协变量的时间路径的方法。这项拟议研究的成功完成将大大改进这两类重要基因组研究的统计方法。

DESCRIPTION (provided by applicant): With advances in DNA sequencing, genotyping, gene annotation,expression profiling, and other high throughput measurement technologies, viable scientific questions are widening in scope and often involve data collected from numerous sources. Statisticians working at the interface of statistics and biology are consequently faced with the challenge of developing analytic methods for investigations involving numerous types of data. 1 important example concerns studies to identify the genetic basis of gene expression (eQTL mapping studies), where relevant data consists of expression measurements, genetic maps, information on co-regulation of transcripts, and on transcription factors and their binding sites. Another collection of studies addresses genetic regulation of physiological systems. The data includes time course expression measurements, physiological variables, and information on co-regulation of transcripts. Expression QTL mapping and time course microarray studies provide fundamental insight into both normal and diseased biological systems. They are being used to identify regulatory genes, to gain insight into the mechanisms of regulation, and to determine ways in which regulation can be modified to promote or maintain a beneficial response. The full extent of biomedical information in these studies cannot be realized without effective statistical methods. The goal of this proposal is to develop, evaluate, and disseminate statistical methods to address questions from these 2 types of studies. This goal will be accomplished through 3 specific aims: the development of methods to identify mapping transcripts and the genomic locations to which they map; the extension of these methods to the cases of both sparse maps and dense maps; and the development of methods to identify temporal paths of expression and affecting covariates. Successful completion of the proposed research will result in substantially improved statistical methods for these 2 important categories of genomic studies.