Biology subjects

Fullam, A.

Publications and source records attributed to Fullam, A..

12 recordsLinked to original sources

bioRxiv2026

A global genomic survey of prokaryotic carbon fixation reveals an oxygen-tolerant rTCA cycle in the surface ocean

Autotrophic carbon fixation, the conversion of inorganic carbon into biomass, underpins life on Earth. Prokaryotes can carry out this process via at least seven biochemically distinct pathways, yet the phylogenetic and environmental distribution of most remains poorly resolved. Screening approximately 40 billion genes from reference genomes, metagenome-assembled genomes (MAGs) and unbinned metagenomic contigs, we provide a global assessment of the phylogeny and ecophysiology of prokaryotic autotrophs. Most pathway marker genes occurred in unbinned contigs and low-quality MAGs, representing phylogenetically distinct lineages absent from isolate genomes and quality filtered MAGs. Established autotrophs accounted for the large majority of pathway detections in quality filtered MAGs, largely recapitulating known biology from cultivated model organisms. Against this backdrop, the reductive TriCarboxylic Acid (rTCA) cycle, long considered restricted to anoxic environments, was detected in three phylogenetically distinct Campylobacterota lineages from oxygenated surface seawater, suggesting a previously unrecognized and unexpected niche for this pathway. We show that all three MAGs share an enzyme variant, previously described in other oxygen-tolerant lineages, that likely underlies their presence in the oxygenated surface ocean. Read mapping across global ocean metagenomes indicates that the organisms carrying it could be far more widespread than the scarcity of recovered MAGs alone would suggest. Together, these findings illustrate that the current view of global autotrophic carbon fixation is largely shaped by what genome-resolved methods can readily recover, while the true phylogenetic and ecological distribution of autotrophic carbon fixation appears to be much broader.

microbiology↗

bioRxiv2026

Planetary structure and drivers of diazotroph communities reveal key reservoirs of nitrogen-fixation potential

Biological nitrogen fixation sustains productivity across Earths ecosystems, yet the diversity, distribution and ecological drivers of nitrogen-fixing prokaryotes (diazotrophs) remain incompletely resolved. Here we screened approximately 40 billion genes to generate a catalogue of 21,157 diazotroph genomes. Using this catalogue, we quantified diazotroph diversity and abundance across 9,163 metagenomes spanning diverse environments. Diazotrophy was distributed across the prokaryotic tree of life, but both gene diversity and metagenomic abundance were dominated by heterotrophic lineages. Freshwater and sedimentary ecosystems emerged as major reservoirs of nitrogen-fixation potential beyond the environments that have historically anchored the field. Diazotroph-rich assemblages were associated with nitrogen and phosphorus limitation together with carbohydrate-rich metabolic regimes, revealing distinct nutrient and energy niches for cyanobacterial and heterotrophic diazotrophs. Together, this framework unifies disparate views of diazotroph diversity, abundance and ecology, providing a foundation for improved prediction of biological nitrogen fixation across Earths ecosystems.

microbiology↗

bioRxiv2026

microntology: a lightweight, data-driven controlled vocabulary to describe Earth's microbial habitats

SummaryWe introduce microntology v1.0, a pragmatic controlled vocabulary of 148 terms to describe microbial habitats and lifestyles, and provide manually curated microntology annotations for >300k metagenomic samples from public repositories. Data Availabilitymicrontology controlled vocabulary terms and term hierarchies 1, and curated annotations for 305,626 metagenomic samples 2 are available via Zenodo and as supplemental tables S1 and S2. User feedback, suggestions and bug reports are welcome under https://github.com/grp-schmidt/microntology/issues.

bioinformatics↗

bioRxiv2025

Metalog: curated and harmonised contextual data for global metagenomics samples

Metagenomic sequencing enables the in-depth study of microbes and their functions in humans, animals and the environment. While sequencing data is deposited in public databases, the associated contextual data is often not complete and needs to be retrieved from primary publications. This lack of access to sample-level metadata like clinical data or in situ observations impedes cross-study comparisons and meta-analyses. We therefore created the Metalog database, a repository of manually curated metadata for metagenomics samples across the globe. It contains 73,082 samples from humans (including 58,506 of the gut microbiome), 10,703 animal samples, 5,146 ocean water samples, and 21,802 samples from other environmental habitats such as soil, sediment, or fresh water. Samples have been consistently annotated for a set of habitat-specific core features, such as demographics, disease status and medication for humans, host species and captivity status for animals, and filter sizes and salinity for marine samples. Additionally, all original metadata is provided in tabular form, simplifying focused studies e.g. into nutrient concentrations. Pre-computed taxonomic profiles facilitate rapid data exploration, while links to the SPIRE database enable genome-based analyses. The database is freely available for browsing and download at https://metalog.embl.de/.

microbiology↗

bioRxiv2025

Planetary microbiome structure and generalist-driven gene flow across disparate habitats

Microbes are ubiquitous on Earth, forming microbiomes that sustain macroscopic life and biogeochemical cycles. Microbial dispersion, driven by natural processes and human activities, interconnects microbiomes across habitats, yet most comparative studies focused on specific ecosystems. To study planetary microbiome structure, function, and inter-habitat interactions, we systematically integrated 85,604 public metagenomes spanning diverse habitats worldwide. Using species-based unsupervised clustering and parameter modeling, we delineated 40 habitat clusters and quantified their ecological similarity. Our framework identified key drivers shaping microbiome structure, such as ocean temperature and host lifestyle. Regardless of biogeography, microbiomes were structured primarily by host-associated or environmental conditions, also reflected in genomic and functional traits inferred from 2,065,975 genomes. Generalists emerged as vehicles thriving and facilitating gene flow across ecologically disparate habitat types, illustrated by generalist-mediated horizontal transfer of an antibiotic resistance island across human gut and wastewater, further dispersing to other habitats, exemplifying human impact on the planetary microbiome.

microbiology↗

bioRxiv2025

A census of hidden and discoverable microbial diversity beyond genome-centric approaches

Cataloguing Earths biodiversity remains one of the most formidable challenges in biology, and the greatest diversity is expected to reside among the smallest organisms: microbes. Yet the ongoing census of microbial life is hampered by disparate sampling of Earths habitats, challenges in isolating uncultivated organisms, limited resolution in taxonomic marker gene amplicons, and incomplete recovery of metagenome-assembled genomes (MAGs). Here, we quantified discoverable bacterial and archaeal diversity in a comprehensive, curated cross-habitat dataset of 92,187 metagenomes. Clustering 502M sequences of 130 marker genes, we detected 705k bacterial and 27k archaeal species-level clades, the vast majority of which was hidden among unbinned contigs. At deeper taxonomic levels, we estimate that 10 archaeal and 145 bacterial novel phyla and around 80k novel genera are discoverable in current data. We identified soils and aquatic environments as novel lineage recovery hotspots, yet predict that discovery will remain in full swing across habitats as more data accrues. Finally, we show that prokaryotic diversity follows power laws, confirming century-old hypotheses on clade size patterns and suggesting that novel lineages arise within common (and fractal) evolutionary patterns, comparable to those among eukaryotic clades and viruses, along the full depth and breadth of the Tree of Life.

microbiology↗

bioRxiv2024

Refined Enterotyping Reveals Dysbiosis in Global Fecal Metagenomes

BackgroundEnterotypes describe human fecal microbiomes grouped by similarity into clusters of microbial community composition, often associated with disease, medications, diet, and lifestyle. Numbers and determinants of enterotypes have been derived by diverse frameworks and applied to cohorts that often lack diversity or inter-cohort comparability. ResultsTo overcome these limitations, we selected 16,772 fecal metagenomes collected from 38 countries to revisit the enterotypes using state-of-the-art fuzzy clustering and found robust clustering regardless of underlying taxonomy, consistent with previous findings. Quantifying the strength of enterotype classifications enriched the enterotype landscape, also reflecting some continuity of microbial compositions. As the classification strength was associated with the patients health status, we established an "Enterotype Dysbiosis Score" (EDS) as a latent covariate for various diseases. ConclusionThis global study confirms the enterotypes, reveals a dysbiosis signal within the enterotype landscape, and enables robust classification of metagenomes with an online "Enterotyper" tool, allowing reproducible analysis in future studies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/607711v3_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1611a2org.highwire.dtl.DTLVardef@dfbb57org.highwire.dtl.DTLVardef@848ac0org.highwire.dtl.DTLVardef@1b15808_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations

The microbiota in individual habitats differ both in relative composition and absolute abundance. While sequencing approaches determine only the relative abundances of taxa and genes, experimental techniques for absolute abundance determination are rarely applied to large-scale microbiome studies. Here, we developed a machine learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data. Applied to large-scale datasets (n = 34,539), we demonstrate that microbial load is the major determinant of gut microbiome variation and associated with numerous host factors. We found that for several diseases, the altered microbial load, not the disease itself, was the main driver of the gut microbiome changes. Adjusting for this effect substantially reduced the significance of more than half of the disease-associated species. Our analysis reveals that the fecal microbial load is a major confounder in microbiome studies, highlighting its importance for understanding microbiome variation in health and disease.

microbiology↗

bioRxiv2023

A catalogue of small proteins from the global microbiome

Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we constructed a global microbial smORFs catalogue (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We found that archaea harbor more small proteins proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.

bioinformatics↗

bioRxiv2022

C. difficile is overdiagnosed in adults and a commensal in infants

Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. To investigate the gut microbiome composition in CDI patients, we analysed 534 metagenomes from 10 publicly available CDI study populations. We then tracked C. difficile on a global scale, screening 42,900 metagenomes from 253 public studies. Among the CDI cohorts, we detected C. difficile in only 30% of the stool samples from CDI patients. However, we found that multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent. In addition, the majority of the investigated studies did not adhere to the recommended guidelines for a correct CDI diagnosis. In the global survey, we found that C. difficile prevalence, abundance and biotic context were age-dependent. C. difficile is a rare taxon associated with reduced diversity in healthy adults, but common and associated with increased diversity in infants. We identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typical of the healthy adult gut microbiome. C. difficile in healthy infants was therefore associated with multiple indicators of healthy gut microbiome maturation. Our analysis raises concerns about potential CDI overdiagnosis and suggests that C. difficile is an important commensal in infants and that its asymptomatic carriage in adults depends on microbial context.

microbiology↗

bioRxiv2021

Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation

Faecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of individual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to individual strains, were the main determinants of individual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.

microbiology↗

bioRxiv2018

Genomic landscape and chronological reconstruction of driver events in multiple myeloma

Multiple myeloma (MM) has a heterogeneous genome, evolving through both pre-clinical and post-diagnosis phases. Here, using sequences from 67 MM genomes serially collected from 30 patients together with public datasets, we establish a hierarchy of driver lesions. Point mutations, structural variants and copy number aberrations define at least 7 genomic subgroups of MM, each with distinct sets of co-operating driver mutations. Complex structural events are major drivers of MM, including chromothripsis, chromoplexy and a replication-based mechanism of templated insertions: these typically occur early. Hyperdiploidy also occurs early, with individual chromosomes often gained in more than one chronological epoch of MM evolution, showing a preferred order of acquisition. Positively selected point mutations frequently occur in later phases of disease development, as do structural variants involving MYC. Thus, initiating driver events of MM, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of subsequent evolution.

cancer biology↗