Mathematical Modeling of DNA Repeats and HIV Epidemics

DNA 重复和 HIV 流行的数学模型

• 批准号: 0616585
• 负责人: James Yorke
• 金额: $ 35万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0616585&HistoricalAwards=false
• 关键词: Mathematical; Modeling; DNA; Repeats; HIV

This project applies the research group's expertise in nonlinear dynamics and mathematical modeling to improve the understanding of two extremely important topics: The propagation of HIV infection and origin and dynamics of repetitive structures in genome. There are many unresolved scientific questions about the transmission of the HIV virus, among them the relative infectivity of people at different stages of the disease and the extent to which people can acquire resistance to the virus. A model for HIV transmission among homosexual men has been developed, based on a detailed data set from the onset of the AIDS crisis in San Francisco. By taking into account the widely varying levels of sexual activity in the population, the data can be fit quite well with parameters that imply a higher late stage infectivity than has been commonly believed. A similar model will be developed for heterosexual HIV transmission and to incorporate additional features into these models, such as acquired resistance and the effect of various prevention measures. By comparing these models with additional data sets, infectivity rates for men and women will be estimated, the effect of acquired resistance will be quantified, and the effectiveness of various prevention strategies will be evaluated. Answering the HIV questions described above will have an impact both on public health policy and on the development of new methods for prevention and treatment of HIV. The results will be critical to understanding the value of screening for infected individuals in slowing the epidemic. Another question studied is the "Repetitive DNA", which refers to separate regions of genomes of various species that are very similar to each other. These repetitive regions are important for several reasons: They are a major obstruction to correctly determining the genomic sequence, they provide valuable information about the evolution of the genome, and in all likelihood they have more biological function than is currently understood. Remarkable statistical features of the repetitive regions for several genomes have been discovered. Long repetitive regions and the mechanisms by which these regions are created, destroyed, and mutated over time are of particular interest. A detailed analysis of the differences between the human and chimpanzee genomes will be performed; in some cases, one genome will have an extra (repetitive) copy of a DNA segment that is in both genomes, and in other cases one genome will be missing a segment that is in the other genome. The processes by which these segments are copied and deleted as a species evolves will be modeled.

该项目应用研究小组在非线性动力学和数学建模方面的专业知识，以提高对两个极其重要的主题的理解：艾滋病毒感染的传播和基因组中重复结构的起源和动力学。 关于艾滋病毒的传播，有许多尚未解决的科学问题，其中包括处于疾病不同阶段的人的相对传染性以及人们对病毒的抵抗力。 根据弗朗西斯科艾滋病危机爆发以来的一组详细数据，已经建立了一个男同性恋者中艾滋病毒传播的模型。考虑到人口中性活动水平的广泛变化，数据可以很好地与暗示比通常认为的更高的晚期感染性的参数相吻合。 将为异性性传播艾滋病毒制定一个类似的模式，并在这些模式中纳入其他特征，如获得性耐药性和各种预防措施的效果。通过将这些模型与其他数据集进行比较，将估计男性和女性的感染率，量化获得性耐药性的影响，并评估各种预防策略的有效性。 讨论上述艾滋病毒问题将对公共卫生政策和制定预防和治疗艾滋病毒的新方法产生影响。这些结果对于理解筛查感染者在减缓流行病方面的价值至关重要。 研究的另一个问题是“重复DNA”，它指的是不同物种基因组中彼此非常相似的独立区域。 这些重复区域很重要，原因有几个：它们是正确确定基因组序列的主要障碍，它们提供了有关基因组进化的有价值的信息，并且它们很可能具有比目前所了解的更多的生物学功能。 一些基因组的重复区域的显著统计特征已经被发现。 长重复区域和这些区域随时间产生、破坏和突变的机制特别令人感兴趣。 将对人类和黑猩猩基因组之间的差异进行详细分析;在某些情况下，一个基因组将具有两个基因组中的DNA片段的额外（重复）拷贝，而在其他情况下，一个基因组将丢失另一个基因组中的片段。 这些片段被复制和删除作为一个物种进化的过程将被建模。