Reviewer #1 (Public Review): Bactabolize: A tool for high-throughput generation of bacterial strain-specific metabolic models

Abstract

Metabolic capacity can vary substantially within a bacterial species, leading to ecological niche separation, as well as differences in virulence and antimicrobial susceptibility. Genome-scale metabolic models are useful tools for studying the metabolic potential of individuals, and with the rapid expansion of genomic sequencing there is a wealth of data that can be leveraged for comparative analysis. However, there exist few tools to construct strain-specific metabolic models at scale.Here we describe Bactabolize (), a reference-based tool which rapidly produces strain-specific metabolic models and growth phenotype predictions. We describe a pan reference model for the priority antimicrobial-resistant pathogen, Klebsiella pneumoniae (github.com/kelwyres/KpSC-pan-metabolic-model), and a quality control framework for using draft genome assemblies as input for Bactabolize.The Bactabolize-derived model for K. pneumoniae reference strain KPPR1 outperformed the CarveMe-derived model across ≥201 substrate and ≥1220 knockout mutant growth predictions. Novel draft genomes passing our systematically-defined quality control criteria resulted in models with a high degree of completeness (≥99% genes and reactions captured) and high accuracy (mean 0.97, n=10).We anticipate the tools and framework described herein will facilitate large-scale metabolic modelling analyses that broaden our understanding of diversity within bacterial species and inform novel control strategies for priority pathogens.