DOI: 10.1101/282251Mar 14, 2018Paper

Automated high-quality reconstruction of metabolic networks from high-throughput data

BioRxiv : the Preprint Server for Biology
Daniel HartlebMartin Lercher

Abstract

While new genomes are sequenced at ever increasing rates, their phenotypic analysis remains a major bottleneck of biomedical research. The generation of genome-scale metabolic models capable of accurate phenotypic predictions is a labor-intensive endeavor; accordingly, such models are available for only a small percentage of sequenced species. The standard metabolic reconstruction process starts from a (semi-)automatically generated draft model, which is then refined through extensive manual curation. Here, we present a novel strategy suitable for full automation, which exploits high-throughput gene knockout or nutritional growth data. We test this strategy by reconstructing accurate genome-scale metabolic models for three strains of Streptococcus, a major human pathogen. The resulting models contain a lower proportion of reactions unsupported by genomic evidence than the most widely used E. coli model, but reach the same accuracy in terms of knockout prediction. We confirm the models' predictive power by analyzing experimental data for auxotrophy, additional nutritional environments, and double gene knockouts, and we generate a list of potential drug targets. Our results demonstrate the feasibility of reconstructing high-quali...Continue Reading

Related Concepts

Related Feeds

Bioinformatics in Biomedicine (Preprints)

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest preprints on bioinformatics in biomedicine here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.