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Estimating bacterial growth dynamics
The pattern of sequencing read coverage of bacteria in metagenomic samples reflects the growth rate. This pattern is predictive of growth because bacterial genomes are circular, with a single origin of replication. So during growth, copies of the genome accumulate at the origin. Korem et al. use the ratio of copy number at the origin to the copy number at the terminus to detect the actively growing species in a microbiome (see the Perspective by Segre). They could spot the difference between virulent and avirulent strains, population diurnal oscillations, species that are growing in irritable bowel disease, and what happens when a host's diet changes. Results were consistent in chemostats, in mice, and in human fecal samples.
Abstract
Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species’ growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes.
