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Friday, February 17, 2023

MVIF.16 February23 Phil Hugenholtz

MVIF.16 February23 Phil Hugenholtz

Does genome contamination compromise the GTDB taxonomy?


Recently, the Bork group published a tool called GUNC (the Genome UNClutter) that detects chimerism and contamination in prokaryotic genomes. Disturbingly, they estimated that 3.2% (1009) of all species in release 95 of the Genome Taxonomy Database (GTDB) consist entirely of contaminated genomes, which could inflate estimates of phylogenetic diversity and taxonomic novelty. We applied GUNC to the latest release of GTDB and found the situation is even worse, with 6.0% (3,958) of all species in release 207 estimated to be comprised entirely of contaminated genomes.

To address the question of whether this contamination compromises the GTDB taxonomy by inflating phylogenetic diversity, we split putative chimeric genomes into halves according to their GUNC contamination scores. We then inferred phylogenetic trees from the genome halves as per the standard GTDB workflow, i.e. based on a concatenated alignment of up to 120 single copy marker genes, to determine any changes in genus to phylum classifications between pairs of genome halves. We also subjected the genome halves to average nucleotide identity (ANI)-based analysis, which is how species are assigned in GTDB. These analyses allowed us to quantify taxonomic inflation caused by genomic contamination, and the extent to which the GTDB taxonomy has been compromised. Tune in to find out the results!

Short Bio

Phil directs the Australian Centre of Ecogenomics at The University of Queensland in Australia. He is a microbiologist who has made substantive contributions in the field of culture-independent analysis of microorganisms. For example, he discovered and characterised several previously unrecognised major bacterial and archaeal lineages, and relevant to this talk, he has led the development of a systematic genome-based classification for prokaryotes.
Dr. Donovan Parks will join us for the Atlantic Q&A

1. Discovery and Characterisation of Temperate Gut Bacteriophages

Bacteriophages are ubiquitous across all environments and influence their bacterial hosts in diverse ways. Within the human gut the bacterial concentration is estimated to be around 1011 cells per gram of faeces, yet the phage concentration is significantly lower at around 109 phages per gram of faeces. However, these raw counts fail to capture the prophages, which are integrated phages residing withing a bacterial host chromosome. Prophages can constitute up to 20% of the host bacterial genome, greatly impacting their host’s function, evolution, and diversification. Here we characterised a large collection of bacterial isolates originating from the human gut and identify their prophage elements. Using a broad panel of induction conditions under anaerobic conditions we identify and begin to experimentally characterise these novel and actively replicating temperate phages of the human gut.

Jeremy Barr
School of Biological Sciences, Monash University, Australia

2. Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55–0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.

William F. Kindschuh & Tal Korem

The Program for Mathematical Genomics, Department of Systems Biology & Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, USA

3. Prebiotic intervention with HAMSAB in untreated essential hypertensive patients assessed in a phase II randomized trial

Fibers remain undigested until they reach the colon, where some are fermented by gut microbiota, producing metabolites called short-chain fatty acids (SCFAs), such as acetate and butyrate1. SCFAs lower blood pressure in experimental models2,3,4,5, but their translational potential is unknown. Here we present the results of a phase II, randomized, placebo-controlled, double-blind cross-over trial (Australian New Zealand Clinical Trials Registry ACTRN12619000916145) using prebiotic acetylated and butyrylated high-amylose maize starch (HAMSAB) supplementation6. Twenty treatment-naive participants with hypertension were randomized to 40 g per day of HAMSAB or placebo, completing each arm for 3 weeks, with a 3-week washout period between them. The primary endpoint was a reduction in ambulatory systolic blood pressure. Secondary endpoints included changes to circulating cytokines, immune markers and gut microbiome modulation. Patients receiving the HAMSAB treatment showed a clinically relevant reduction in 24-hour systolic blood pressure independent of age, sex and body mass index without any adverse effects. HAMSAB increased levels of acetate and butyrate, shifted the microbial ecosystem and expanded the prevalence of SCFA producers. In summary, a prebiotic intervention with HAMSAB could represent a promising option to deliver SCFAs and lower blood pressure in patients with essential hypertension.

Hamdi Jama

School of Biological Sciences, Monash University, Australia

4. The role of the gut microbiota in shaping responses to vaccination

Global vaccination programs have been enormously successful, dramatically reducing the rates of vaccine-preventable diseases. However, for reasons that are poorly understood, these responses are highly variable between individuals. It is becoming increasingly apparent that the composition and function of the gut microbiota is a critical factor modulating immune responses to vaccination, and when the gut microbiota is disrupted, such as with antibiotic exposure, it may lead to suboptimal vaccine responses (e.g. lower antibody titres).

At the Lynn Systems Immunology group we use multi-omic technologies to study the relationship between the gut microbiota and vaccine responses in both humans and preclinical murine models. Here, I will report on findings from the Antibiotics and Immune Responses (AIR) study which followed 170 infants for the first 15 months of life to assess how early life antibiotic exposure shapes the composition of the gut microbiota, immune function and responses to scheduled infant vaccinations.

Feargal Ryan
NHMRC Investigator, Computational & Systems Biology Program,  SAHMRI, Australia