A Systems Approach to Genomic Signal Processing: From Signal Extraction to Regulatory Intervention

基因组信号处理的系统方法：从信号提取到监管干预人类基因组计划最近宣布了人类基因组的测序，这具有巨大的潜在影响，如定制药物。需要新的分析方法和计算技术来实现这一承诺。这项研究的重点是开发和集成信号处理方法，以帮助诊断和治疗癌症等疾病。高通量微阵列技术产生的海量数据为发现在机制水平上解释特定疾病的关键基因和基因组合、在分子水平上对疾病进行分类以及开发各种疾病的最佳治疗策略提供了一条途径。这项研究涉及(I)为功能基因组学中出现的单个子问题开发基于信号处理的解决方案；以及(Ii)确保这些解决方案可以拼凑在一起，为疾病诊断和治疗的原始整体问题提供解决方案。基于微阵列的基因组信号处理大致可分为五类：信号提取、聚类、表型分类(诊断)、建立遗传调控网络模型，以及制定调控干预(治疗)的策略。五个类别之间往往有一个自然的等级，因此，从系统的角度进行研究，以确定在一个级别上的处理、分析和估计通过系统传播以影响下游分析的方式，以及类别内的从属问题如何相互作用。这些问题是在一个统一的理论框架内解决的，它们的解决方案被应用于实际的生物学问题，并开发了大量的集成软件，为进一步的研究和应用提供了便利。

A Systems Approach to Genomic Signal Processing: Signal Extraction to Regulatory InterventionThe Human Genome Project recently announced the sequencing of the human genome with enormous potential implications such as customized medicine. New analytic methods and computational technologies are needed to fulfill this promise. This study focuses on the development and integration of signal processing approaches for aiding the diagnosis and treatment of diseases such as cancer. The massive amount of data generated by high-throughput microarray technology provides a gateway to the discovery of key genes and gene combinations that explain specific diseases on a mechanistic level, to the classification of diseases on a molecular level, and to the development of optimal therapeutic strategies for various diseases. This study is concerned with (i) developing signal processing based solutions to individual sub-problems that arise in functional genomics; and (ii) ensuring that these solutions can be pieced together to provide solutions to the original overall problems of disease diagnosis and therapy.Microarray-based genomic signal processing can be broadly broken into five categories: signal extraction, clustering, classification of phenotypes (diagnosis), modeling genetic regulatory networks, and developing strategies for regulatory intervention (therapy). There tends to be a natural hierarchy among the five categories which are, therefore, studied from a systems perspective to ascertain the manner in which processing, analysis, and estimation on one level propagates through the system to affect downstream analyses, and how the subordinate issues within a category interact among each other. These questions are addressed within a unified theoretical framework, their solutions are applied to real biological problems, and a large body of integrated software to facilitate further investigation and application is developed.