ANALYTICAL ASPECTS OF MOLECULAR EPIDEMIOLOGY

描述：新的，新出现的和重新出现的传染病构成了一个 对公共卫生的威胁日益增加，随之而来的是健康状况恶化 护理费用。 作为回应，疾病控制和预防中心 (CDC)推荐了一种前线策略，包括扩大使用分子 流行病学 然而，在成功实施之前， 分析问题的统计处理的结果数据必须是 解决了 本研究旨在解决围绕分析的问题 片段数据带模式（DNA指纹），产生于许多 基因分型技术应用于传染性有机体。 这些关切 与更先进的DNA法医学应用有很大不同 人类的指纹 尽管所提出的方法侧重于 结核病，由此产生的统计方法将普遍适用于 生物和基因分型技术。 这些分析工具在以下方面至关重要： 充分认识到丰富的分子流行病学数据的潜力， 是如此的重要，因此，被广泛获得。 的 本申请的具体目的将解决：1）评估各种 用于比较微生物DNA指纹图谱的方法，包括 适应测量误差的来源，发展和比较 相似性/距离度量，扩展这些度量以处理多个 基因分型系统和其中条带强度是重要的系统，以及 为了评估将个人指纹与大型指纹匹配的重要性， 指纹数据库; 2）统计技术的属性， 表示这些数据，包括聚类和系统发育算法; 以及3）将这些分析与流行病学和临床数据相结合， 鉴定病原体的人际传播和细菌克隆， 具有独特的致病特性。 碎片数据目前正在使用 因为它们比DNA序列数据具有许多优势。 这些优点包括技术简单和成本相对较低， 在大样本量的流行病学研究中。 然而，一个缺点 缺乏各种统计分析方法 数据类型。 本申请旨在弥补这一缺陷，从而 增强相关分子基因分型技术在 收集防治传染病的数据。

DESCRIPTION: New, emerging and re-emerging infectious diseases pose an ever-increasing threat to public health, with attendant escalation of health care costs. In response, the Centers for Disease Control and Prevention (CDC) recommended a front line strategy involving expanded use of molecular epidemiology. Yet, before this can be successfully implemented, multiple analytic issues for statistical handling of the resultant data must be resolved. This study proposes to address concerns surrounding the analysis of fragment data band patterns (DNA fingerprints) that arise from numerous genotyping techniques applied to infectious organisms. These concerns differ substantially from the far more developed forensic use of DNA fingerprints in humans. Although the approaches proposed focus on tuberculosis, the resulting statistical methodology will generalize across organisms and genotyping techniques. Such analytic tools are crucial in fully realizing the potential of the rich, molecular epidemiologic data that is of such vital importance and, accordingly, is being widely obtained. The Specific Aims of this application will address: 1) evaluating various methods for comparing microbial DNA fingerprint patterns including accommodating sources of measurement error, developing and comparing similarity/distance measures, extending these measures to handle multiple genotyping systems and to systems where band intensity is consequential, and to assess significance of matching individual fingerprints to large fingerprint databases; 2) properties of statistical techniques for representing these data including clustering and phylogenetic algorithms; and 3) integrating these analyses with epidemiologic and clinical data to identify interpersonal transmission of pathogens, and bacterial clones which have distinct pathogenic properties. Fragment data are currently being used extensively because of the many advantages they have over DNA sequence data. These include technical simplicity and relatively low cost, permitting use in epidemiologic studies with large sample sizes. However, a disadvantage is the absence of the variety of statistical analytical approaches to this type of data. This application seeks to redress this deficiency, thereby enhancing the utility of the associated molecular genotyping techniques in the collection of data for combating infectious disease.