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许多方面的理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，已经允许对HIV和HCV等病毒的流行结构进行定量描述。来自研究队列和常规临床护理的系统发育方法应用于具有高密度目标人群覆盖率的病毒序列的本地数据集，已用于传播相关性、疫苗效力评估和公共卫生的各个方面的研究。潜在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现在可以从序列数据中推断出来并建立模型。在本项目中，我们将结合群体遗传学、序列进化和网络理论开发更多创新的病原体传播模型，提供有效的方法实现和可扩展到全球尺度数据集的快速近似算法，评估预防和治疗方法对五种局部流行的HIV和HCV的流行动态的影响，并建立这些和其他病原体的普遍流行模型。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，从而最好地确定目标，以最有效和最节省地使用预防干预措施。

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.