Tanaka Mark M, Francis Andrew R
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052, Australia.
Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15266-71. doi: 10.1073/pnas.0603130103. Epub 2006 Oct 2.
The W-Beijing strain of tuberculosis has been identified in many molecular epidemiological studies as being particularly prevalent. This identification has been made possible through the development of a number of genotyping technologies including spoligotyping. Highly prevalent genotypes associated with outbreaks, such as the W-Beijing strain, are implicitly regarded as fast spreading. Here we present a quantitative method to identify "emerging" strains, those that are spreading faster than the background rate inferred from spoligotype data. The approach uses information about the mutation process specific to spoligotypes, combined with a model of both transmission and mutation. The core principle is that if two comparable strains have the same number of isolates, then the strain with fewer inferred mutation events must have spread faster if the mutation process is common. Applying this method to four different data sets, we find not only the W-Beijing strain, but also a number of other strains, to be emerging in this sense. Importantly, the strains that are identified as emerging are not simply those with the largest number of cases. The use of this method should facilitate the targeting of individual genotypes in intervention programs.
在许多分子流行病学研究中,结核分枝杆菌的W-北京株被确定为特别普遍。通过开发包括间隔寡核苷酸分型(spoligotyping)在内的多种基因分型技术,才使得这种鉴定成为可能。与疫情爆发相关的高度流行基因型,如W-北京株,被含蓄地认为传播速度很快。在这里,我们提出一种定量方法来识别“新兴”菌株,即那些传播速度比从间隔寡核苷酸分型数据推断出的背景速率更快的菌株。该方法利用了特定于间隔寡核苷酸分型的突变过程信息,并结合了传播和突变模型。核心原理是,如果两个可比菌株的分离株数量相同,那么如果突变过程是常见的,推断突变事件较少的菌株一定传播得更快。将这种方法应用于四个不同的数据集,我们发现不仅W-北京株,还有许多其他菌株在这个意义上是新兴的。重要的是,被确定为新兴的菌株并不只是那些病例数最多的菌株。这种方法的使用应该有助于在干预项目中针对个体基因型。