DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: METABOLIC: high-throughput profiling of microbial genomes for functional traits, metabolism, biogeochemistry, and community-scale functional networks

Journal Article · · Microbiome

Background Advances in microbiome science are being driven in large part due to our ability to study and infer microbial ecology from genomes reconstructed from mixed microbial communities using metagenomics and single-cell genomics. Such omics-based techniques allow us to read genomic blueprints of microorganisms, decipher their functional capacities and activities, and reconstruct their roles in biogeochemical processes. Currently available tools for analyses of genomic data can annotate and depict metabolic functions to some extent; however, no standardized approaches are currently available for the comprehensive characterization of metabolic predictions, metabolite exchanges, microbial interactions, and microbial contributions to biogeochemical cycling. Results We present METABOLIC (METabolic And BiogeOchemistry anaLyses In miCrobes), a scalable software to advance microbial ecology and biogeochemistry studies using genomes at the resolution of individual organisms and/or microbial communities. The genome-scale workflow includes annotation of microbial genomes, motif validation of biochemically validated conserved protein residues, metabolic pathway analyses, and calculation of contributions to individual biogeochemical transformations and cycles. The community-scale workflow supplements genome-scale analyses with determination of genome abundance in the microbiome, potential microbial metabolic handoffs and metabolite exchange, reconstruction of functional networks, and determination of microbial contributions to biogeochemical cycles. METABOLIC can take input genomes from isolates, metagenome-assembled genomes, or single-cell genomes. Results are presented in the form of tables for metabolism and a variety of visualizations including biogeochemical cycling potential, representation of sequential metabolic transformations, community-scale microbial functional networks using a newly defined metric “MW-score” (metabolic weight score), and metabolic Sankey diagrams. METABOLIC takes ~ 3 h with 40 CPU threads to process ~ 100 genomes and corresponding metagenomic reads within which the most compute-demanding part of hmmsearch takes ~ 45 min, while it takes ~ 5 h to complete hmmsearch for ~ 3600 genomes. Tests of accuracy, robustness, and consistency suggest METABOLIC provides better performance compared to other software and online servers. To highlight the utility and versatility of METABOLIC, we demonstrate its capabilities on diverse metagenomic datasets from the marine subsurface, terrestrial subsurface, meadow soil, deep sea, freshwater lakes, wastewater, and the human gut. Conclusion METABOLIC enables the consistent and reproducible study of microbial community ecology and biogeochemistry using a foundation of genome-informed microbial metabolism, and will advance the integration of uncultivated organisms into metabolic and biogeochemical models. METABOLIC is written in Perl and R and is freely available under GPLv3 at https://github.com/AnantharamanLab/METABOLIC.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
National Library of Medicine (NLM); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1891286
Journal Information:
Microbiome, Journal Name: Microbiome Journal Issue: 1 Vol. 10; ISSN 2049-2618
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

References (74)

Microbial genomes retrieved from High Arctic lake sediments encode for adaptation to cold and oligotrophic environments journal January 2020
Biogeochemical Models: Implicit versus Explicit Microbiology book January 2001
Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle journal January 2019
Microorganisms and their roles in fundamental biogeochemical cycles journal June 2011
BlastKOALA and GhostKOALA: KEGG Tools for Functional Characterization of Genome and Metagenome Sequences journal February 2016
The Thaumarchaeota: an emerging view of their phylogeny and ecophysiology journal June 2011
Modular Architecture of Metabolic Pathways Revealed by Conserved Sequences of Reactions journal February 2013
Single-cell genomics reveals the lifestyle of Poribacteria, a candidate phylum symbiotically associated with marine sponges journal July 2010
Microbial metagenomes from three aquifers in the Fennoscandian shield terrestrial deep biosphere reveal metabolic partitioning among populations journal October 2015
Metagenomic resolution of microbial functions in deep-sea hydrothermal plumes across the Eastern Lau Spreading Center journal June 2015
dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication journal July 2017
Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea journal August 2017
A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life journal August 2018
Thousands of microbial genomes shed light on interconnected biogeochemical processes in an aquifer system journal October 2016
Gut microbiome development along the colorectal adenoma–carcinoma sequence journal March 2015
Fast gapped-read alignment with Bowtie 2 journal March 2012
Fast and sensitive protein alignment using DIAMOND journal November 2014
A new view of the tree of life journal April 2016
Erratum: Genomic inference of the metabolism of cosmopolitan subsurface Archaea, Hadesarchaea journal January 2016
The microbial nitrogen-cycling network journal February 2018
Diversity and biogeography of SAR11 bacteria from the Arctic Ocean journal September 2019
Gammaproteobacteria mediating utilization of methyl-, sulfur- and petroleum organic compounds in deep ocean hydrothermal plumes journal August 2020
Genome diversification in globally distributed novel marine Proteobacteria is linked to environmental adaptation journal May 2020
Depth-discrete metagenomics reveals the roles of microbes in biogeochemical cycling in the tropical freshwater Lake Tanganyika journal February 2021
Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life journal September 2017
Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface journal January 2018
Mediterranean grassland soil C–N compound turnover is dependent on rainfall and depth, and is mediated by genomically divergent microorganisms journal May 2019
HydDB: A web tool for hydrogenase classification and analysis journal September 2016
Evidence for hydrogen oxidation and metabolic plasticity in widespread deep-sea sulfur-oxidizing bacteria journal December 2012
Metabolic dependencies drive species co-occurrence in diverse microbial communities journal May 2015
Evolution of the 3-hydroxypropionate bicycle and recent transfer of anoxygenic photosynthesis into the Chloroflexi journal September 2017
The BioCyc collection of microbial genomes and metabolic pathways journal August 2017
Pathway Tools version 23.0 update: software for pathway/genome informatics and systems biology journal December 2019
The Sequence Alignment/Map format and SAMtools journal June 2009
BamTools: a C++ API and toolkit for analyzing and managing BAM files journal April 2011
GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database journal November 2019
KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold journal November 2019
Decoding molecular interactions in microbial communities journal July 2016
KEGG: Kyoto Encyclopedia of Genes and Genomes journal January 2000
DRAM for distilling microbial metabolism to automate the curation of microbiome function journal August 2020
metaGEM: reconstruction of genome scale metabolic models directly from metagenomes journal October 2021
MetaCyc: a multiorganism database of metabolic pathways and enzymes journal January 2006
TIGRFAMs and Genome Properties: tools for the assignment of molecular function and biological process in prokaryotic genomes journal January 2007
KAAS: an automatic genome annotation and pathway reconstruction server journal May 2007
KEGG for linking genomes to life and the environment journal December 2007
HMMER web server: interactive sequence similarity searching journal May 2011
Pfam: the protein families database journal November 2013
The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST) journal November 2013
Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors journal November 2015
eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences journal November 2015
UniProt: a worldwide hub of protein knowledge November 2018
eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses journal November 2018
dbCAN2: a meta server for automated carbohydrate-active enzyme annotation journal May 2018
Fast automated reconstruction of genome-scale metabolic models for microbial species and communities journal June 2018
Microbial metabolism and adaptations in Atribacteria ‐dominated methane hydrate sediments journal July 2021
Microbial syntrophy: interaction for the common good journal May 2013
Microbial arsenic: from geocycles to genes and enzymes journal August 2002
A 3-Hydroxypropionate/4-Hydroxybutyrate Autotrophic Carbon Dioxide Assimilation Pathway in Archaea journal December 2007
Untangling Genomes from Metagenomes: Revealing an Uncultured Class of Marine Euryarchaeota journal February 2012
Sulfur Oxidation Genes in Diverse Deep-Sea Viruses journal May 2014
It Takes a Village: Microbial Communities Thrive through Interactions and Metabolic Handoffs journal March 2018
Prodigal: prokaryotic gene recognition and translation initiation site identification journal March 2010
Current status and applications of genome-scale metabolic models journal June 2019
gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models journal March 2021
Genomic resolution of linkages in carbon, nitrogen, and sulfur cycling among widespread estuary sediment bacteria journal April 2015
MEGAN Community Edition - Interactive Exploration and Analysis of Large-Scale Microbiome Sequencing Data journal June 2016
Development of HuMiChip for Functional Profiling of Human Microbiomes journal March 2014
Intergenomic Comparisons Highlight Modularity of the Denitrification Pathway and Underpin the Importance of Community Structure for N2O Emissions journal December 2014
Microbes as Engines of Ecosystem Function: When Does Community Structure Enhance Predictions of Ecosystem Processes? journal February 2016
Characterization of the Microbiome at the World’s Largest Potable Water Reuse Facility journal October 2018
Diversity and Biogeography of SAR11 Bacteria from the Arctic Ocean dataset January 2019
gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models collection January 2021
Metage2Metabo, microbiota-scale metabolic complementarity for the identification of key species journal December 2020
Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3 journal May 2021

Cited By (8)

Additional file 2 of Efficient management of the nitritation-anammox microbiome through intermittent aeration: absence of the NOB guild and expansion and diversity of the NOx reducing guild suggests a highly reticulated nitrogen cycle dataset January 2022
Additional file 3 of Efficient management of the nitritation-anammox microbiome through intermittent aeration: absence of the NOB guild and expansion and diversity of the NOx reducing guild suggests a highly reticulated nitrogen cycle dataset January 2022
Additional file 2 of Variable impact of geochemical gradients on the functional potential of bacteria, archaea, and phages from the permanently stratified Lac Pavin dataset January 2023
Additional file 2 of Stratified microbial communities in Australia’s only anchialine cave are taxonomically novel and drive chemotrophic energy production via coupled nitrogen-sulphur cycling dataset January 2023
Additional file 1 of Genomic analyses reveal a low-temperature adapted clade in Halorubrum, a widespread haloarchaeon across global hypersaline environments dataset January 2023
Additional file 2 of Genomic analyses reveal a low-temperature adapted clade in Halorubrum, a widespread haloarchaeon across global hypersaline environments dataset January 2023
Additional file 3 of Genomic analyses reveal a low-temperature adapted clade in Halorubrum, a widespread haloarchaeon across global hypersaline environments dataset January 2023
Additional file 1 of Genomics-based identification of a cold adapted clade in Deinococcus dataset January 2024