Benchmarking Community-Wide Estimates of Growth Potential from Metagenomes Using Codon Usage Statistics

Trait inference from mixed-species assemblages is a central problem in microbial ecology. Frequently, sequencing information from an environment is available, but phenotypic measurements from individual community members are not. With the increasing availability of molecular data for microbial communities, bioinformatic approaches that map metagenome to (meta)phenotype are needed. Recently, we developed a tool, gRodon, that enables the prediction of the maximum growth rate of an organism from genomic data on the basis of codon usage patterns. Our work and that of other groups suggest that such predictors can be applied to mixed-species communities in order to derive estimates of the average communitywide maximum growth rate. Here, we present an improved maximum growth rate predictor designed for metagenomes that corrects a persistent GC bias in the original gRodon model for metagenomic prediction. We benchmark this predictor with simulated metagenomic data sets to show that it has superior performance on mixed-species communities relative to earlier models. We go on to provide guidance on data preprocessing and show that calling genes from assembled contigs rather than directly from reads dramatically improves performance. Finally, we apply our predictor to large-scale metagenomic data sets from marine and human microbiomes to illustrate how community-wide growth prediction can be a powerful approach for hypothesis generation. Altogether, we provide an updated tool with clear guidelines for users about the uses and pitfalls of metagenomic prediction of the average community-wide maximal growth rate.