Biology subjects

Parks, D. H.

Publications and source records attributed to Parks, D. H..

15 recordsLinked to original sources

bioRxiv2026

gTranslate: rapid and accurate translation table prediction for prokaryotic genomes

BackgroundBioinformatic tools often require the prediction of protein-coding genes to make inferences about prokaryotic genomes. Typically, the genetic code used for translating genes to proteins must be specified by the user based on the taxonomic classification of a genome assembly or, for some widely used tools, established using a heuristic rule based on gene coding densities. Manual specification is at best inconvenient, but more challenging is that many bioinformatic tools are applied before taxonomic classifications have been established making specifying the translation table impractical. MethodsHere we provide a computationally efficient tool, gTranslate, that uses an ensemble of five machine learning methods to accurately predict translation tables for prokaryotic genomes. The feature vector used by gTranslate takes advantage of differences in gene coding densities when predicting genes under different translation tables along with features that consider the number and ratio of UGA stop codon reassignments to tryptophan or glycine. ResultsWe demonstrate that gTranslate correctly predicts the translation table of prokaryotic genomes >99.99% of the time (i.e. <1 error per 10,000 genomes) and outperforms a more computationally expensive prediction method and a coding density heuristic used by popular bioinformatic tools. Using gTranslate, we identify a basal lineage of Ca. Stammera capleta that uses the standard bacterial genetic code instead of the UGA stop codon to tryptophan reassignment common to other members of this species. We also identify the first instances of UGA-to-tryptophan reassignment in the Patescibacteriota making this the first bacterial phylum with members capable of using translation tables 4, 11, and 25.

bioinformatics↗

bioRxiv2025

First report of stop codon reassignment to tryptophan in members of the bacterial phylum Actinomycetota

Reassignment of stop codons is a significant evolutionary event with recoding of UGA to tryptophan being previously identified in only three bacterial phyla, the Bacillota, Pseudomonadota, and Verrucomicrobiota. Here, we present genomic evidence of this recoding in a fourth bacterial phylum, the Actinomycetota, specifically in the family Eggerthellaceae. We identify the UGA stop-to-tryptophan reassignment in 34 metagenome-assembled genomes recovered from the stool samples of diverse mammalian hosts, including equids and primates. Canonical markers for this reassignment are consistently observed including conserved UGA codons aligning to tryptophan, loss of release factor 2 (prfB), and presence of a tRNATrp(UCA) gene. We infer that this reassignment occurred at least twice as the lineages containing recoded genomes are paraphyletic, forming two distinct groups separated by a third lineage with strains that continue to use UGA as a stop codon. These lineages represent three new Eggerthellaceae genera for which we propose the type species Equivita altericodex, Gorillivita intestinalis, and Tapirivita inops reflecting isolation source and genomic properties. Genomes representing these genera, including the non-recoded Tapirivita lineage, have reduced genomes and complete or partial loss of biosynthetic pathways, suggesting a transition to obligate symbiosis. Increasing host dependency may have facilitated stop codon reassignment in Equivita and Gorillivita species. This work expands the known phylogenetic diversity of UGA stop-to-tryptophan reassignment in the bacterial domain and establishes the Eggerthellaceae as a new focal point for understanding the evolutionary drivers of genetic code plasticity.

evolutionary biology↗

bioRxiv2024

A rational approach for the targeted discovery and characterisation of microbiome-derived therapeutics

The human gut microbiome is intrinsically involved in health and disease, representing a wealth of untapped therapeutic potential. Here, we demonstrate the utility and potential of a metagenome guided, large cohort-based approach for the rational selection of live biotherapeutics from the human gut. We applied this approach to Inflammatory Bowel Disease (IBD), identifying several lead candidates that were significantly depleted in individuals with IBD compared to healthy controls. Their therapeutic potential was assessed in preclinical models of IBD where they improved markers of disease pathology by reducing inflammation and promoting mucosal healing and wound repair. All leads had excellent safety profiles in silico and in vitro, and several additionally presented favourable manufacturing properties, supporting their progression into clinical trials. We believe that this rational approach will be generalisable to any disease state with underlying microbiome aetiology and will expedite the development of novel microbiome-derived therapeutics to improve human health.

microbiology↗

bioRxiv2024

AnnoView enables large-scale analysis, comparison, and visualization of microbial gene neighborhoods

The analysis and comparison of gene neighborhoods is a powerful approach for exploring microbial genome structure, function, and evolution. Although numerous tools exist for genome visualization and comparison, genome exploration across large genomic databases or user-generated datasets remains a challenge. Here, we introduce AnnoView, a web server designed for interactive exploration of gene neighborhoods across the bacterial and archaeal tree of life. Our server offers users the ability to identify, compare, and visualize gene neighborhoods of interest from 30,238 bacterial genomes and 1,672 archaeal genomes, through integration with the comprehensive GTDB and AnnoTree databases. Identified gene neighborhoods can be visualized using pre-computed functional annotations from different sources such as KEGG, Pfam, and TIGRFAM, or clustered based on similarity. Alternatively, users can upload and explore their own custom genomic datasets in GBK, GFF, or CSV format, or use AnnoView as a genome browser for relatively small genomes (e.g., viruses and plasmids). Ultimately, we anticipate that AnnoView will catalyze biological discovery by enabling user-friendly search, comparison, and visualization of genomic data. AnnoView is available at http://annoview.uwaterloo.ca

bioinformatics↗

bioRxiv2022

GTDB-Tk v2: memory friendly classification with the Genome Taxonomy Database

The Genome Taxonomy Database (GTDB) and associated taxonomic classification toolkit (GTDB-Tk) have been widely adopted by the microbiology community. However, the growing size of the GTDB bacterial reference tree has resulted in GTDB-Tk requiring substantial amounts of memory (~320 GB) which limits its adoption and ease of use. Here we present an update to GTDB-Tk that uses a divide-and-conquer approach where user genomes are initially placed into a bacterial reference tree with family-level representatives followed by placement into an appropriate class-level subtree comprising species representatives. This substantially reduces the memory requirements of GTDB-Tk while having minimal impact on classification. AvailabilityGTDB-Tk is implemented in Python and licenced under the GNU General Public Licence v3.0. Source code and documentation are available at: https://github.com/ecogenomics/gtdbtk. Contactp.chaumeil@uq.edu.au or donovan.parks@gmail.com

bioinformatics↗

bioRxiv2022

CheckM2: a rapid, scalable and accurate tool for assessing microbial genome quality using machine learning

Advances in DNA sequencing and bioinformatics have dramatically increased the rate of recovery of microbial genomes from metagenomic data. Assessing the quality of metagenome-assembled genomes (MAGs) is a critical step prior to downstream analysis. Here, we present CheckM2, an improved method of predicting the completeness and contamination of MAGs using machine learning. We demonstrate the effectiveness of CheckM2 on synthetic and experimental data, and show that it outperforms the original version of CheckM in predicting MAG quality. CheckM2 is substantially faster than CheckM and its database can be rapidly updated with new high-quality reference genomes. We show that CheckM2 accurately predicts genome quality for MAGs from novel lineages, even those with sparse genomic representation, or reduced genome size (e.g. symbionts) such as those found in the Patescibacteria and the DPANN superphylum. CheckM2 provides accurate genome quality predictions across the microbial tree of life, giving increased confidence when inferring novel biological conclusions from MAGs.

bioinformatics↗

bioRxiv2021

Reclassification of Shigella species as later heterotypic synonyms of Escherichia coli in the Genome Taxonomy Database

Members of the genus Shigella have high genomic similarity to Escherichia coli and are often considered to be atypical members of this species. In an attempt to retain Shigella species as recognizable entities, they were reclassified as Escherichia species in the Genome Taxonomy Database (GTDB) using an operational average nucleotide identity (ANI)-based approach nucleated around type strains. This resulted in nearly 80% of E. coli genomes being reclassified to new species including the common laboratory strain E. coli K-12 (to E. flexneri) because it is more closely related to the type strain of Shigella flexneri than it is to the type strain of E. coli. Here we resolve this conundrum by treating Shigella species as later heterotypic synonyms of E. coli, present evidence supporting this reclassification, and show that assigning E. coli/Shigella strains to a single species is congruent with the GTDB-adopted genomic species definition.

microbiology↗

bioRxiv2020

Evidence for non-methanogenic metabolisms in globally distributed archaeal clades basal to the Methanomassiliicoccales

Recent discoveries of mcr and mcr-like complexes in genomes from diverse archaeal lineages suggest that methane (and more broadly alkane) metabolism is an ancient pathway with complicated evolutionary histories. The conventional view is that methanogenesis is an ancestral metabolism of the archaeal class Thermoplasmata. Through comparative genomic analysis of 12 Thermoplasmata metagenome-assembled genomes (MAGs), we show that these microorganisms do not encode the genes required for methanogenesis, which suggests that this metabolism may have been laterally acquired by an ancestor of the order Methanomassiliicoccales. These MAGs include representatives from four orders basal to the Methanomassiliicoccales, including a high-quality MAG (95% complete) that likely represents a new order, Ca. Lunaplasma lacustris ord. nov. sp. nov. These MAGs are predicted to use diverse energy conservation pathways, such as heterotrophy, sulfur and hydrogen metabolism, denitrification, and fermentation. Two of these lineages are globally widespread among anoxic, sedimentary environments, with the exception of Ca. Lunaplasma lacustris, which has thus far only been detected in alpine caves and subarctic lake sediments. These findings advance our understanding of the metabolic potential, ecology, and global distribution of the Thermoplasmata and provide new insights into the evolutionary history of methanogenesis within the Thermoplasmata.

microbiology↗

bioRxiv2020

A rank-normalized archaeal taxonomy based on genome phylogeny resolves widespread incomplete and uneven classifications

An increasing wealth of genomic data from cultured and uncultured microorganisms provides the opportunity to develop a systematic taxonomy based on evolutionary relationships. Here we propose a standardized archaeal taxonomy, as part of the Genome Taxonomy Database (GTDB), derived from a 122 concatenated protein phylogeny that resolves polyphyletic groups and normalizes ranks based on relative evolutionary divergence (RED). The resulting archaeal taxonomy is stable under a range of phylogenetic variables, including marker genes, inference methods, corrections for rate heterogeneity and compositional bias, tree rooting scenarios, and expansion of the genome database. Rank normalization was shown to robustly correct for substitution rates varying up to 30-fold using simulated datasets. Taxonomic curation follows the rules of the International Code of Nomenclature of Prokaryotes (ICNP) while taking into account proposals to formally recognise the rank of phylum and to use genome sequences as type material. The taxonomy is based on 2,392 quality screened archaeal genomes, the great majority of which (93.3%) required one or more changes to their existing taxonomy, mostly as a result of incomplete classification. In total, 16 archaeal phyla are described, including reclassification of three major monophyletic units from the former Euryarchaeota and one phylum resulting from uniting the TACK superphylum into a single phylum. The taxonomy is publicly available at the GTDB website (https://gtdb.ecogenomic.org).

microbiology↗

bioRxiv2020

Diverse Arctic lake sediment microbiota shape methane emission temperature sensitivity

Northern post-glacial lakes are a significant and increasing source of atmospheric carbon (C), largely through ebullition (bubbling) of microbially-produced methane (CH4) from the sediments1. Ebullitive CH4 flux correlates strongly with temperature, suggesting that solar radiation is the primary driver of these CH4 emissions2. However, here we show that the slope of the temperature-CH4 flux relationship differs spatially, both within and among lakes. Hypothesizing that differences in microbiota could explain this heterogeneity, we compared site-specific CH4 emissions with underlying sediment microbial (metagenomic and amplicon), isotopic, and geochemical data across two post-glacial lakes in Northern Sweden. The temperature-associated increase in CH4 emissions was greater in lake middles--where methanogens were more abundant--than edges, and sediment microbial communities were distinct between lake edges and middles. Although CH4 emissions projections are typically driven by abiotic factors1, regression modeling revealed that microbial abundances, including those of CH4-cycling microorganisms and syntrophs that generate H2 for methanogenesis, can be useful predictors of porewater CH4 concentrations. Our results suggest that deeper lake regions, which currently emit less CH4 than shallower edges, could add substantially to overall CH4 emissions in a warmer Arctic with longer ice-free seasons and that future CH4 emission predictions from northern lakes may be improved by accounting for spatial variations in sediment microbiota.

microbiology↗

bioRxiv2020

Lateral gene transfer drives metabolic flexibility in the anaerobic methane oxidising archaeal family Methanoperedenaceae

Anaerobic oxidation of methane (AOM) is an important biological process responsible for controlling the flux of methane into the atmosphere. Members of the archaeal family Methanoperedenaceae (formerly ANME-2d) have been demonstrated to couple AOM to the reduction of nitrate, iron, and manganese. Here, comparative genomic analysis of 16 Methanoperedenaceace metagenome-assembled genomes (MAGs), recovered from diverse environments, revealed novel respiratory strategies acquired through lateral gene transfer (LGT) events from diverse archaea and bacteria. Comprehensive phylogenetic analyses suggests that LGT has allowed members of the Methanoperedenaceae to acquire genes for the oxidation of hydrogen and formate, and the reduction of arsenate, selenate and elemental sulfur. Numerous membrane-bound multi-heme c type cytochrome complexes also appear to have been laterally acquired, which may be involved in the direct transfer of electrons to metal oxides, humics and syntrophic partners. ImportanceAOM by microorganisms limits the atmospheric release of the potent greenhouse gas methane and has consequent importance to the global carbon cycle and climate change modelling. While the oxidation of methane coupled to sulphate by consortia of anaerobic methanotrophic (ANME) archaea and bacteria is well documented, several other potential electron acceptors have also been reported to support AOM. In this study we identify a number of novel respiratory strategies that appear to have been laterally acquired by members of the Methanoperedenaceae as they are absent in related archaea and other ANME lineages. Expanding the known metabolic potential for members of the Methanoperedenaceae provides important insight into their ecology and suggests their role in linking methane oxidation to several global biogeochemical cycles.

microbiology↗

bioRxiv2019

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

Comprehensive reference data is essential for accurate taxonomic and functional characterization of the human gut microbiome. Here we present the Unified Human Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 million protein sequences used to generate the Unified Human Gastrointestinal Protein (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome remains to be fully explored, with over 70% of the UHGG species lacking cultured representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-species genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which were specific to individual human populations. These freely available genomic resources should greatly facilitate investigations into the human gut microbiome.

microbiology↗

bioRxiv2019

Selection of representative genomes for 24,706 bacterial and archaeal species clusters provide a complete genome-based taxonomy

We recently introduced the Genome Taxonomy Database (GTDB), a phylogenetically consistent, genome-based taxonomy providing rank normalized classifications for nearly 150,000 genomes from domain to genus. However, nearly 40% of the genomes used to infer the GTDB reference tree lack a species name, reflecting the large number of genomes in public repositories without complete taxonomic assignments. Here we address this limitation by proposing 24,706 species clusters which encompass all publicly available bacterial and archaeal genomes when using commonly accepted average nucleotide identity (ANI) criteria for circumscribing species. In contrast to previous ANI studies, we selected a single representative genome to serve as the nomenclatural type for circumscribing each species with type strains used where available. We complemented the 8,792 species clusters with validly or effectively published names with 15,914 de novo species clusters in order to assign placeholder names to the growing number of genomes from uncultivated species. This provides the first complete domain to species taxonomic framework which will improve communication of scientific results.

microbiology↗

bioRxiv2018

AnnoTree: visualization and exploration of a functionally annotated microbial tree of life

Bacterial genomics has revolutionized our understanding of the microbial tree of life; however, mapping and visualizing the distribution of functional traits across bacteria remains a challenge. Here, we introduce AnnoTree - an interactive, functionally annotated bacterial tree of life that integrates taxonomic, phylogenetic, and functional annotation data from nearly 24,000 bacterial genomes. AnnoTree enables visualization of millions of precomputed genome annotations across the bacterial phylogeny, thereby allowing users to explore gene distributions as well as patterns of gene gain and loss across bacteria. Using AnnoTree, we examined the phylogenomic distributions of 28,311 gene/protein families, and measured their phylogenetic conservation, patchiness, and lineage-specificity. Our analyses revealed widespread phylogenetic patchiness among bacterial gene families, reflecting the dynamic evolution of prokaryotic genomes. Genes involved in phage infection/defense, mobile elements, and antibiotic resistance dominated the list of most patchy traits, as well as numerous intriguing metabolic enzymes that appear to have undergone frequent horizontal transfer. We anticipate that AnnoTree will be a valuable resource for exploring gene histories across bacteria, and will act as a catalyst for biological and evolutionary hypothesis generation.

bioinformatics↗

bioRxiv2018

A proposal for a standardized bacterial taxonomy based on genome phylogeny

Taxonomy is a fundamental organizing principle of biology, which ideally should be based on evolutionary relationships. Microbial taxonomy has been greatly restricted by the inability to obtain most microorganisms in pure culture and, to a lesser degree, the historical use of phenotypic properties as the basis for classification. However, we are now at the point of obtaining genome sequences broadly representative of microbial diversity by using culture-independent techniques, which provide the opportunity to develop a comprehensive genome-based taxonomy. Here we propose a standardized bacterial taxonomy based on a concatenated protein phylogeny that conservatively removes polyphyletic groups and normalizes ranks based on relative evolutionary divergence. From 94,759 bacterial genomes, 99 phyla are described including six major normalized monophyletic units from the subdivision of the Proteobacteria, and amalgamation of the Candidate Phyla Radiation into the single phylum Patescibacteria. In total, 73% of taxa had one or more changes to their existing taxonomy.

microbiology↗