Lineage-specific microbial protein prediction enables large-scale exploration of protein ecology within the human gut

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Microbes use a range of genetic codes and gene structures, yet these are ignored during metagenomic analysis. This causes spurious protein predictions, preventing functional assignment which limits our understanding of ecosystems. To resolve this, we developed a lineage-specific gene prediction approach that uses the correct genetic code based on the taxonomic assignment of genetic fragments, removes partial predictions, and optimises prediction of small proteins. Applied to 9,634 metagenomes and 3,594 genomes from the human gut, this approach increased the landscape of captured expressed microbial proteins by 78.9%, including previously hidden functional groups. Optimised small protein prediction captured 3,772,658 small protein clusters, many with antimicrobial activity. Integration of the protein sequences and sample metadata into a tool, InvestiGUT, enables association of protein prevalence with host parameters. Accurate prediction of proteins is critical for understanding the functionality of microbiomes, hence this work will enhance understanding mechanistic interactions between microbes and hosts.

Authors 4

1. Matthias A. Schmitz Aachen Functional Microbiome Research Group Functional Microbiome Research Group

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, RWTH University Hospital;

   Functional Microbiome Research Group, RWTH University Hospital

2. Nicholas J Dimonaco

   Queen's University Belfast · Aberystwyth University · McMaster University

   Affiliation as printed

   McMaster University; Queen's University Belfast; Aberystwyth University

   Aberystwyth University

   McMaster University

   Queen's University Belfast

3. Thomas Clavel Aachen Functional Microbiome Research Group Functional Microbiome Research Group

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, RWTH University Hospital;

   Functional Microbiome Research Group, RWTH University Hospital

4. Thomas C. A. Hitch corresponding Aachen Functional Microbiome Research Group Functional Microbiome Research Group

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, RWTH University Hospital;

   Functional Microbiome Research Group, RWTH University Hospital