Modeling Epidemic Infectious Diseases Using Sequence Analysis

描述(由申请人提供)：系统发育分析在增加我们对病毒和细菌病原体生物学的许多方面的了解方面发挥了至关重要的作用。序列数据进化分析的最新进展，包括时间戳数据和深度测序，使定量描述艾滋病毒和丙型肝炎病毒等病毒的流行结构成为可能。从研究队列和常规临床护理应用于具有高密度覆盖目标人群的病毒序列的本地数据集的系统发育方法已被用于传播相关性、疫苗效力评估和公共卫生的各个方面的研究。现在可以从序列数据中推断并模拟基本传播网络的非随机结构、其在流行病中的作用及其对治疗和预防的影响。在这个项目中，我们将结合种群遗传学、序列进化和网络理论，开发更多创新的病原体传播模型，提供高效的方法实现和可扩展到全球规模数据集的快速近似算法，评估预防和治疗方法对艾滋病毒和丙型肝炎局部流行的影响，并对这些病原体和其他病原体的普遍流行进行建模。通过开发结合和分析病原体序列和其他流行病学数据的计算和统计方法，我们将能够推断和描述传播网络，以最好地确定最有效和最节俭地使用预防干预措施的目标。

DESCRIPTION (provided by applicant): Phylogenetic analysis has played a crucial role in increasing our understanding of many aspects of viral and bacterial pathogen biology. Recent advances in evolutionary analysis of sequence data, including time- stamped data and deep sequencing, have allowed quantitative description of epidemic structure for viruses like HIV and HCV. Phylogenetic approaches applied to local datasets of viral sequences with high density coverage of the target population, both from research cohorts and routine clinical care, have been used in studies of transmission correlates, vaccine efficacy evaluation, and various aspects of public health. The non- random structure of the underlying transmission network, its role in the epidemic and its implications for treatment and prevention can now be inferred from sequence data and modeled. In this project, we will develop more innovative models of pathogen transmission combining population genetics, sequence evolution, and network theory, provide efficient method implementation and fast approximate algorithms scalable to global-scale datasets, evaluate the effect of prevention and treatment approaches on epidemic dynamics in five localized epidemics of HIV and HCV, and model generalized epidemics for these and other pathogens. By developing computational and statistical methods that incorporate and analyze pathogen sequence and other epidemiologic data, we will be able to infer and characterize transmission networks to best identify targets for the most effective and parsimonious use of prevention interventions.