Salamon H, Segal M R, Ponce de Leon A, Small P M
University of California, San Francisco, USA.
Emerg Infect Dis. 1998 Apr-Jun;4(2):159-68. doi: 10.3201/eid0402.980203.
Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is positively correlated for fragments within a lane, an align-and-count method that compensates for relative scaling of lanes reliably counts matching fragments between lanes. Results of a two-step method we developed to cluster identical fingerprints agree closely with 5 years of computer-assisted visual matching among 1,335 M. tuberculosis fingerprints. Fully documented and validated methods of automated comparison and clustering will greatly expand the scope of molecular epidemiology.
传染病的分子流行病学研究依赖于病原体基因型比较，这种比较通常会产生由DNA片段集（DNA指纹）组成的模式。我们使用一种高度发达的基因分型系统，即基于IS6110的结核分枝杆菌限制性片段长度多态性分析，来开发一种能自动比较大量指纹的计算方法。由于片段长度测量中的误差与片段长度成正比，并且对于同一泳道内的片段呈正相关，因此一种补偿泳道相对缩放的比对计数方法能够可靠地计算泳道间匹配的片段。我们开发的用于聚类相同指纹的两步法结果与1335个结核分枝杆菌指纹在5年的计算机辅助视觉匹配结果非常吻合。经过充分记录和验证的自动比较和聚类方法将极大地扩展分子流行病学的范围。
