Benchmarking microbial growth rate predictions from metagenomes

Abstract

Growth rates are central to understanding microbial interactions and community dynamics. Metagenomic growth estimators have been developed, specifically codon usage bias (CUB) for maximum growth rates and “peak-to-trough ratio” (PTR) for in situ rates. Both were originally tested with pure cultures, but natural populations are more heterogeneous, especially in individual cell histories pertinent to PTR. To test these methods, we compared predictors with observed growth rates of freshly collected marine prokaryotes in unamended seawater. We prefiltered and diluted samples to remove grazers and greatly reduce virus infection, so net growth approximated gross growth. We sampled over 44 h for abundances and metagenomes, generating 101 metagenome-assembled genomes (MAGs), including Actinobacteria, Verrucomicrobia, SAR406, MGII archaea, etc. We tracked each MAG population by cell-abundance-normalized read recruitment, finding growth rates of 0 to 5.99 per day, the first reported rates for several groups, and used these rates as benchmarks. PTR, calculated by three methods, rarely correlated to growth (r ~−0.26–0.08), except for rapidly growing γ-Proteobacteria (r ~0.63–0.92), while CUB correlated moderately well to observed maximum growth rates (r = 0.57). This suggests that current PTR approaches poorly predict actual growth of most marine bacterial populations, but maximum growth rates can be approximated from genomic characteristics.

Estimating maximal microbial growth rates from cultures, metagenomes, and single cells via codon usage patterns

“…S6). This is consistent with previous work showing that CUB-based approaches can predict growth rates in low-nutrient marine microcosms (15).…”

“…There are any number of reasons why an organism may not reproduce at its physiological maximal rate (e.g., fluctuating habitat quality, dispersal to suboptimal habitats, etc.). Nevertheless, it is encouraging that recent work using natural communities has shown that CUB-based estimators do a reasonably good job of predicting observed instantaneous growth rates in marine systems (15), even as peak to trough (77-80) methods of estimating growth have been reported to work poorly for marine plankton, with the exception of the most highly abundant copiotrophs (15). Thus, taken together with our benchmarking against nutrient enrichment experiments, the data suggest that CUB-based estimators of maximal growth rate tend to also capture the instantaneous growth rate of a community, likely by approximating the relative proportion of copiotrophs to oligotrophs in a system.…”

“…A beacon of hope, maximal growth rates predicted using genome-wide codon usage statistics (9), appear to capture over-all trends in the growth rates of natural communities (15). Because the genetic code is degenerate, genes may vary in their usage of alternative codons for a given amino acid.…”

Umibato: estimation of time-varying microbial interaction using continuous-time regression hidden Markov model

“…Adopting the PTR-based growth rate estimation enables using cross-sectional datasets. However, the performance of PTR-based methods is questionable ( Long et al , 2020 ), and the use of this method should be considered carefully.…”

Umibato: estimation of time-varying microbial interaction using continuous-time regression hidden Markov model

“…Adopting the PTR-based growth rate estimation enables using cross-sectional datasets. However, the performance of PTR-based methods is questionable (Long et al, 2020), and the use of this method should be considered carefully. Simulated abundance Figure 6: Simulated interaction state and bacterial abundance trajectories.…”