ANALYTICAL ASPECTS OF MOLECULAR EPIDEMIOLOGY

描述：新的、新出现的和再次出现的传染病构成 对公众健康的威胁与日俱增，随之而来的是健康的升级 护理费用。对此，疾病控制和预防中心 美国疾病控制与预防中心(CDC)建议了一个涉及扩大分子使用的前线战略 流行病学。然而，在这一点能够成功实施之前， 对结果数据进行统计处理的分析问题必须是 解决了。这项研究建议解决围绕分析的担忧 片段数据条带模式(DNA指纹) 应用于感染性生物的基因分型技术。这些担忧 与更先进的DNA法医使用有很大的不同 人类身上的指纹。尽管提议的方法侧重于 结核病，由此产生的统计方法将推广到 生物体和基因分型技术。这样的分析工具在 充分认识到丰富的分子流行病学数据的潜力 是如此重要，因此，正在被广泛获得。这个 本申请的具体目标将涉及：1)评估各种 比较微生物DNA指纹图谱的方法包括 适应测量误差源，发展和比较 相似性/距离度量，扩展这些度量以处理多个 基因分型系统和条带强度有影响的系统，以及 评估将单个指纹与大指纹进行匹配的重要性 指纹数据库.2)统计技术的特性 代表这些数据，包括聚类和系统发育算法； 3)将这些分析与流行病学和临床数据相结合，以 确定病原体的人际传播，以及 具有明显的致病特性。当前正在使用片段数据 这是因为它们比DNA序列数据具有许多优势。 这些包括技术简单和相对较低的成本，允许使用 在大样本量的流行病学研究中。然而，一个劣势是 是缺乏对此的各种统计分析方法 数据类型。本申请试图纠正这一缺陷，从而 加强相关分子基因分型技术在人类疾病中的应用 收集与传染病作斗争的数据。

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.