Amir, AmnonZeisel, AmitZuk, OrElgart, MichaelStern, ShayShamir, OhadTurnbaugh, PeterSoen, YoavShental, Noam2014-03-112013Amir, Amnon, Amit Zeisel, Or Zuk, Michael Elgart, Shay Stern, Ohad Shamir, Peter J. Turnbaugh, Yoav Soen, and Noam Shental. 2013. “High-resolution microbial community reconstruction by integrating short reads from multiple 16S rRNA regions.” Nucleic Acids Research 41 (22): e205. doi:10.1093/nar/gkt1070. http://dx.doi.org/10.1093/nar/gkt1070.0305-1048http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879554The emergence of massively parallel sequencing technology has revolutionized microbial profiling, allowing the unprecedented comparison of microbial diversity across time and space in a wide range of host-associated and environmental ecosystems. Although the high-throughput nature of such methods enables the detection of low-frequency bacteria, these advances come at the cost of sequencing read length, limiting the phylogenetic resolution possible by current methods. Here, we present a generic approach for integrating short reads from large genomic regions, thus enabling phylogenetic resolution far exceeding current methods. The approach is based on a mapping to a statistical model that is later solved as a constrained optimization problem. We demonstrate the utility of this method by analyzing human saliva and Drosophila samples, using Illumina single-end sequencing of a 750 bp amplicon of the 16S rRNA gene. Phylogenetic resolution is significantly extended while reducing the number of falsely detected bacteria, as compared with standard single-region Roche 454 Pyrosequencing. Our approach can be seamlessly applied to simultaneous sequencing of multiple genes providing a higher resolution view of the composition and activity of complex microbial communities.en-USJournal Article2014-03-1110.1093/nar/gkt1070