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Veseli, I.

Publications and source records attributed to Veseli, I..

6 recordsLinked to original sources

Synteny-aware microbial pangenome graphs reveal blueprints of genomic variation

Pangenomics quantifies the conserved and variable gene repertoire among genomes, but popular implementations ignore gene synteny. Graph-based approaches incorporate both gene homology and synteny, but become difficult to interpret due to pervasive rearrangements. Here we present network-pruning and graph-layout algorithms that enable interactive, synteny-aware quantification and visualization of gene conservation and variability. Applied to 29 genomes of the marine genus Undatipelagibacter (formerly SAR11 subclade Ia.3.VI), we find that genomic variability forms not a few hypervariable islands against a static backbone but a structured continuum, whose variable regions differ in scale, topology, function, and evolutionary character. Genome variation spans from ancient, specialized regions of hundreds of genes whose propensity to vary is conserved across genera, to single hypervariable genes shaped by epistatic co-selection with partners dispersed genome-wide, and shows that chromosomal context carries evolutionary information synteny-unaware pangenomics cannot capture, and some evolutionary processes act on entire functional subsystems throughout a pangenome.

microbiology↗

Digital Microbe: A Genome-Informed Data Integration Framework for Collaborative Research on Emerging Model Organisms

The remarkable pace of genomic data generation is rapidly transforming our understanding of life at the micron scale. Yet this data stream also creates challenges for team science. A single microbe can have multiple versions of genome architecture, functional gene annotations, and gene identifiers; additionally, the lack of mechanisms for collating and preserving advances in this knowledge raises barriers to community coalescence around shared datasets. "Digital Microbes" are frameworks for interoperable and reproducible collaborative science through open source, community-curated data packages built on a (pan)genomic foundation. Housed within an integrative software environment, Digital Microbes ensure real-time alignment of research efforts for collaborative teams and facilitate novel scientific insights as new layers of data are added. Here we describe two Digital Microbes: 1) the heterotrophic marine bacterium Ruegeria pomeroyi DSS-3 with >100 transcriptomic datasets from lab and field studies, and 2) the pangenome of the cosmopolitan marine heterotroph Alteromonas containing 339 genomes. Examples demonstrate how an integrated framework collating public (pan)genome-informed data can generate novel and reproducible findings.

bioinformatics↗

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health versus IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

microbiology↗

A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut

Plasmids are extrachromosomal genetic elements that often encode fitness enhancing features. However, many bacteria carry cryptic plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes, and is 14 times as numerous as crAssphage, currently established as the most abundant genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from ones mother. pBI143 can transfer between Bacteroidales and although it does not appear to impact bacterial host fitness in vivo, can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an inexpensive alternative for detecting human colonic inflammatory states.

microbiology↗

Heterotrophic bacterial diazotrophs are more abundant than their cyanobacterial counterparts in metagenomes covering most of the sunlit ocean

Biological nitrogen fixation is a major factor contributing to microbial primary productivity in the open ocean. The current view depicts a few cyanobacterial diazotrophs as the most relevant marine nitrogen fixers, whereas heterotrophic diazotrophs are more diverse and considered to have lower impacts on the nitrogen balance. Here, we used 891 Tara Oceans metagenomes to create a manually curated, non-redundant genomic database corresponding to free-living, as well as filamentous, colony-forming, particle-attached and symbiotic bacterial and archaeal populations occurring in the surface of five oceans and two seas. Notably, the database provided the genomic content of eight cyanobacterial diazotrophs including Trichodesmium populations and a newly discovered population similar to Richelia, as well as 40 heterotrophic bacterial diazotrophs organized into three main functional groups that considerably expand the known diversity of abundant marine nitrogen fixers compared to previous genomic surveys. Critically, these 48 populations may account for more than 90% of cells containing known nifH genes and occurring in the sunlit ocean, suggesting that the genomic characterization of the most abundant marine diazotrophs may be nearing completion. The newly identified heterotrophic bacterial diazotrophs are widespread, express their nifH genes in situ, and co-occur under nitrate-depleted conditions in large size fractions where they might form aggregates providing the low-oxygen microenvironments required for nitrogen fixation. Most significantly, we found heterotrophic bacterial diazotrophs to be more abundant than cyanobacterial diazotrophs in most metagenomes from the open oceans and seas. This large-scale environmental genomic survey emphasizes the considerable potential of heterotrophs in the marine nitrogen balance.

microbiology↗

Adaptive ecological processes and metabolic independence drive microbial colonization and resilience in the human gut

Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments, and reveal taxon-independent markers of dysbiosis that may explain why widespread yet typically low abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

microbiology↗