Latent class analysis (LCA) has allowed epidemiologists to overcome the practical constraints faced by traditional diagnostic test evaluation methods, which require both a gold standard diagnostic test and ample numbers of appropriate reference samples. Over the past four decades, LCA methods have expanded to allow epidemiologists to evaluate diagnostic tests and estimate true prevalence using imperfect tests over a variety of complex data structures and scenarios, including during the emergence of novel infectious diseases. The objective of this review is to provide an overview of recent developments in LCA methods, as well as a practical guide to applying Bayesian LCA (BLCA) to the evaluation of diagnostic tests. Before conducting a BLCA, the suitability of BLCA for the pathogen of interest, the availability of appropriate samples, the number of diagnostic tests, and the structure of the data should be carefully considered. While formulating the model, the model's structure and specification of informative priors will affect the likelihood that useful inferences can be drawn. With the growing need for advanced analytical methods to evaluate diagnostic tests for newly emerging diseases, LCA is a promising field of research for both the veterinary and medical disciplines.
1Metagenomic studies have revolutionized the study of novel phages. However these studies 2 trade the depth of coverage for breadth. In this study we show that the targeted sequencing of a 3 phage genomic region as small as 200-300 base pairs, can provide sufficient sequence diversity to 4 serve as an individual-specific barcode or "Phageprint". The targeted approach reveals a high-5 resolution view of phage communities that is not available through metagenomic datasets. By 6 creating instructional videos and collection kits, we enabled citizen scientists to gather ~700 oral 7 samples spanning ~100 individuals residing in different parts of the world. In examining phage 8 communities at 6 different oral sites, and by comparing phage communities of individuals living 9 across the globe, we were able to study the effect of spatial separation, ranging from several 10 millimeters to thousands of kilometers. We found that the spatial separation of just a few 11 centimeters (the distance between two oral sites) can already result in highly distinct phage 12 community compositions. For larger distances, spanning the phage communities of different 13 individuals living in different parts of the world, we did not observe any correlation between spatial 14 distance and phage community composition as individuals residing in the same city did not have any 15 more similar phage communities than individuals living on different continents. Additionally, we 16 found that neither genetics nor cohabitation seem to play a role in the relatedness of phage 17 community compositions across individuals. Cohabitating siblings and even identical twins did not 18 have phage community compositions that were any more similar than those of unrelated individuals. 19The primary factor contributing to phage community composition relatedness is direct contact 20 between two habitats, as is demonstrated by the similarity between oral phage community 21 compositions of partners. Furthermore, by exploring phage communities across the span of a 22 month, and in some cases several years, we observed highly stable community compositions. These 23 3 studies consistently point to the existence of remarkably diverse and personal phage families that are 24 stable in time and apparently present in people around the world. 25 26 Due to the immense sequence diversity of phage genomes (48-50), an in-depth view of their 78 communities through a targeted sequencing approach could provide novel insights. As such, the 79 overarching aim of this study was to explore oral phage communities and their inter-and intra-80 personal diversity, their spatial patterns of distribution, as well as temporal dynamics in a large-scale 81 and high-resolution fashion. Towards this aim, we first had to choose regions within phage genomes 82 on which to perform targeted sequencing. Because of the vast diversity of uncultured phages, we 83 relied on oral metagenomic datasets to identify candidate marker sequences from such phages. 84We have described the methods for phage marker dis...
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